Mild Cognitive Impairment (MCI) is a diagnostic category indicating cognitive impairment which does not meet diagnostic criteria for dementia such as Alzheimer’s disease. There are public health concerns about Alzheimer’s disease (AD) prompting intervention strategies to respond to predictions about the impacts of ageing populations and cognitive decline. This relationship between MCI and AD rests on three interrelated principles, namely, that a relationship exists between AD and MCI, that MCI progresses to AD, and that there is a (...) reliable system of classification of MCI. However, there are also several ethical issues and problems arising in the AD/MCI relationship. These include early diagnosis and interventions, the effects on people with MCI, and the newer neuroimaging and neuropharmacological approaches used in diagnosis and treatment. All these issues pose questions about the principles of MCI in relation to AD, with implications for how MCI is understood, diagnosed, treated, and experienced by patients. This article analyses four challenging areas for neuroethics: the definition and diagnosis of MCI; MCI in relation to AD; clinical implications of MCI for ethical disclosure, diagnosis, and treatment; and the research implications of MCI. The significant connections between these areas are often overlooked, together with uncertainties overall. Patients, healthcare systems and society are best served by informed clinicians, academics and researchers. After 35 years, the store of MCI knowledge is expanding and evolving. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Mild Cognitive Impairment Is RelevantRonald C. Petersen (bio)Keywordsaging, Alzheimer’s disease, dementia, mild cognitive impairment, pharmaceutical industryGraham and Ritchie (2006) have contributed a scholarly document that implores us to reexamine nosological categories and certain diagnostic outcomes. They have chosen mild cognitive impairment (MCI) as the target of their scrutiny and have raised several interesting issues. I would like to comment on their approach and (...) suggest that MCI is a useful clinical entity that does serve a practical function and hopefully will lead to a better quality of life for aging persons.There are several clarifications concerning the construct of MCI that need to be emphasized. Graham and Ritchie have asserted that all persons with MCI eventually evolve to Alzheimer's disease (AD) and have claimed that this is the inevitable outcome of the disorder. Although it is true that many of the early studies on MCI focused on the amnestic subtype as a precursor to AD (Bennett et al. 2002; Ganguli, Dodge, Shen, and DeKosky 2004; Lopez et al. 2003; Petersen et al. 1999), subsequent work has expanded the construct to include prodromal forms of other disorders (Petersen 2004; Winblad et al. 2004). As such, the construct of MCI has become flexible in recent years to account for alternative types of intermediate cognitive impairment.The authors state that MCI addresses those individuals speculated to have an inevitable dementia. Certainly, we do not presume that dementia is inevitable in the aging process; rather, we posit that if certain criteria are fulfilled in persons who are aging, the likelihood of a person progressing to a certain type of dementia is quite high. As such, this is an important precondition about which to learn, because interventional strategies may be available.Graham and Ritchie argue that some cognitive changes with aging are "normal" and trying to classify these individuals as "abnormal" is performing a disservice to much of the aging population. We draw an important distinction between the cognitive changes of normal aging, as they are recognized to exist, and what we feel constitutes the pathologic changes of MCI. We believe that the abnormal cognitive function found in MCI has a high probability of progressing to a greater degree of cognitive dysfunction in a relatively short period of time and these behavioral changes are accompanied by pathologic brain changes that are manifested on magnetic resonance imaging scans, positron emission tomography scans, cerebrospinal fluid biomarkers, and autopsy studies (Hampel et al. 2004; Jack et al. 1999; Markesbery et al. [End Page 45] 2006; Petersen et al. 2006). This type of progression is in contradistinction to other individuals who are experiencing cognitive changes of normal aging. These individuals do not progress rapidly to greater degrees of impairment and autopsy studies reveal that their brains do not harbor the pathologic changes found in the MCI population (Knopman et al. 2003).The cognitive and behavioral changes accompanying persons with MCI are devastating and cannot be ascribed to "senility" or "He is just getting old." It is a mistake to imply that by labeling people with a condition such as MCI we are doing them a disservice. Most of these individuals are seeking medical attention for their perceived difficulties. Consequently, addressing these concerns and educating the individuals on the implications of their symptoms are important services. Although we may not have adequate therapies at present, this does not imply that we should ignore the symptoms.We cannot treat many conditions at present, yet we do not avoid the opportunity to characterize the condition and make a diagnosis. Even if this were part of the aging process, this does not mean that we should ignore the disability and refuse to treat it. Most individuals develop an inflexibility of their optical lenses as they age, yet corrective lenses of one type or another are believed to be extremely beneficial at alleviating this disability associated with the aging phenomenon. No one would argue that it is inappropriate to treat this condition because it is "just a part of aging."It should be noted that I have stressed the situation in which individuals are seeking medical attention for their cognitive concerns. It is quite a different situation if an... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Mild Cognitive Impairment:Where Does It Go From Here?John Bond (bio) and Lynne Corner (bio)Keywordsbiomedicalization, dementia, mild cognitive impairment, subjectivityThe joy of formal interdisciplinary discussion of this kind is the way that ideas presented through the gaze of social scientists stimulate such exciting thoughts and responses from other disciplines such as philosophy and psychology. We would like to thank Sabat and Thornton for their supportive and (...) provocative reactions to our paper. In the spirit of their responses, it is not our intention to respond to their thoughts directly; rather, we take the opportunity to theorize sociologically about this new category of psychiatry that has come to be known simply as mild cognitive impairment (MCI). In reviewing the responses of Sabat and Thornton, three thoughts emerged. First, together we have covered ontologic, epistemologic, methodologic, and theoretical questions about MCI, but none of us has posed basic political questions, such as: Why has MCI emerged as a new psychiatric label at this particular time? Second, this discussion brings together social scientists with a psychologist and a philosopher, but important constituents are missing. Consequently we are missing "insider" views on the importance of MCI to clinical practice. Third, this discussion highlights for us even more acutely the central question: Is MCI a real entity? In the following, we reflect on the first of these because our response also addresses the third. We first revisit the "evidence" about the importance of MCI for clinical practice.The notion of MCI as the transitional state between normal aging and Alzheimer's disease and other dementias has existed in a number of guises for many years, with benign senescent forgetfulness (Kral 1962) being the forerunner of a number of other terms, including questionable dementia, incipient dementia, isolated memory impairment, mild neurocognitive decline, age-associated memory impairment, age-associated cognitive decline, and cognitive-impairment-not-demented (Geda et al. 2004). Given that psychiatric labels implying the existence of MCI have been part of the practice landscape for over forty years, it is perhaps not surprising that its reinvention in the form of MCI has not, it appears, raised much attention outside specialist centers in North America and Europe. The reaction from grassroots clinical practice has been similar in intensity to their subdued reaction to the antipsychiatry movement in the 1960s. But for specialist clinics like the Mayo Clinic in Rochester, Minnesota, it has been an expanding [End Page 29] industry with numerous published papers, international conference presentations, and research funding opportunities.MCI can be distinguished from similar diagnostic categories that preceded its appearance in 1991. A key diagnostic criteria is the requirement for a subjective memory complaint by the person subsequently diagnosed as having MCI. Other diagnostic criteria include normal general cognitive function, normal activities of daily living, and memory being impaired for age, but not being demented (Petersen et al. 1999; Petersen and Morris 2003). To our knowledge, the idea of subjectivity being an important diagnostic criterion, as opposed to a means of identifying signs and symptoms, is a first in medical science. We know of no other medical category or diagnosis where subjectivity plays such a significant role, other than perhaps severe health phobias. Broadly speaking, two kinds of clinical evidence for MCI exist: first, that originating from studies (some quite small) applying the diagnostic criteria in specialist clinic populations; and, second, that found in large population studies. The main distinction between these two sets of evidence is that one is based on selected clinic populations and the other on unselected community populations. Most studies conclude that people whose memory is impaired for their age, as measured by similar cognitive tests such as the Mini-Mental State Examination, show decline in cognition that often leads to Alzheimer's disease and other kinds of dementia in the future. This finding is not remarkable given that it has long been known that age is a predictor of cognitive impairment. However, the population studies suggest a lower conversion rate than those for specialist clinics (Ritchie, Artero, and Touchon 2001).Petersen (2005) provides a robust defense as to why MCI might be a useful category in research and also indicates the potential benefits of treating MCI... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Mild Cognitive Impairment:What's in a Name?Steven R. Sabat (bio)Keywordslabeling, mild cognitive impairment, recall memory, selfhood, stereotype threatCorner and Bond (2006) raise a number of important conceptual issues related to the problems involved in defining mild cognitive impairment (MCI), differentiating it from normal aging, the definition of normal aging itself, and ethical issues surrounding the possible adverse effects of a diagnosis of MCI on (...) the individuals thus described. It would seem that portentous ramifications are involved and that clarifying the conceptual issues would be of great value, not only to researchers but also to the ever-growing population of elderly people. In what follows, I address some of these issues further.Problems of Definition and MeasurementOne of the problems that the authors discuss at the outset of their article concerns what methods are appropriate for detecting those with MCI: "Neuropsychological tests alone do not discriminate between normal aged-related memory loss and MCI or dementia and clinical judgment remains central to diagnosis" (Corner and Bond 2006, 5). Of course, to be able to discriminate between normal aged-related memory problems and MCI, we must first be able to define the former. What exactly is normal? As the authors correctly point out, the term has different meanings, one being normative (usual), another being nonpathologic. Is it normal (usual) for some sort of breakdown to occur in brain systems as a function of increased age? If so, is there a threshold age below which the very same physiologic breakdown is unusual? Would such a threshold age, if one existed, be the same for everyone, regardless of genotype and the cumulative interactive effects of nutrition, health, and stress-related factors over a period of decades? In effect, is some sort of memory impairment part of the natural (usual) process of aging for some people at particular ages rather than for others? And exactly what does it mean to be mildly impaired in the cognitive domain?Hogan and McKeith (2001) presented a working group's definition characterizing MCI such that people who complain about memory problems and who also provide objective evidence of such problems, yet who simultaneously display "normal general cognitive function and intact activities of daily living" (Hogan and McKeith 2001, 1131), should be identified and followed. Here again, however, we confront the problem of defining "normal general cognitive function" as well as "normal activities of daily living." Can one have normal general cognitive function without normal memory function? If so, what exactly constitutes [End Page 13] general cognitive function and on what conceptual or theoretical basis is such a definition valid? Furthermore, what sort of memory function are we talking about? Memory can be said to involve a number of stages: encoding, storage, and retrieval. Retrieval can be of the explicit type (conscious recall or recognition of specific information) with which people with Alzheimer's disease (AD) often reveal deficits or of the implicit type (a change in behavior as a result of previous experience of which the person may have no conscious recollection) as demonstrated in people with AD (Knopman and Nissen 1987). That is, people with AD can display deficits in explicit memory functions without similar deficits simultaneously in implicit memory functions.A partial answer to the question about memory loss in MCI may be found in the use of the Mini-Mental State Examination (MMSE; Folstein, Folstein, and McHugh 1975), originally intended to be used as a screening device, but employed more and more frequently as an outcome measure to assess cognitive decline as well as the efficacy of drug treatments. Although the examination purports to test orientation, registration, attention, calculation, recall, language (naming, repeating, reading, writing, three-stage command), and construction, a task analysis reveals that the test is not quite as "global" in the cognitive domain as it is purported to be. For example, ten of the maximum thirty points on the examination are earned for "orientation" in time and place. Yet, all of the questions in this section of the test require intact recall of the relevant information. For example, if a person is asked, "What day of the week is this?" and replies "I don't know," the... (shrink)

The evolution of a relevant nosological concept reflects changes in the distinction between what is recognized and defined as normal and pathologic. Attention is directed to the rationale and value of detecting subclinical aging-related modifications in cognitive performance. The position that different kinds of dementias may have precedents in etiological-specific kinds of early or mild cognitive impairments (MCI) supports targeting people earlier for study of these subclinical symptoms. Because heterogeneous disorders can be expected to have multiple patterns of cognitive (...) and behavioral changes, useful conceptual nosologies should be flexible. Yet clinical research primarily restricts its focus to a single pathway where MCI leads to Alzheimer's disease (AD), and uses selective recruitment, washout screenings, repeated trialing of similar compounds, and other methods that bank the published evidence in favor of the existing therapies and their modest efficacy. This focus on AD recursively colors MCI, not as a flexible "human kind" in need of more careful research, but like AD, as an essential "natural kind." Early determination of MCI targets a potential pharmaceutical market of a quarter to a half of the population over sixty-five and the individual experiencing cognitive decline in its early stages is aware and sensitive to their surroundings, to a linked sociodegeneration with neurodegeneration. This paper examines how classifying people changes both the classifier and the subject of classification. The potential for conflict of interest is raised regarding what new causal knowledge and techniques for ascertainment are selected. Reading evidence from epidemiology, neurology, and clinical studies through science studies and bioethics lenses, we explore the possibility of a pluralistic model of cognitive impairment nosology where biological/pathologic processes respond and interrelate with a normal healthy state. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Mild Cognitive Impairment:Which Kind Is It?Andy Hamilton (bio)Keywordshuman kinds, mild cognitive impairment, multiple personality disorder, practical kinds, social constructionThere is much stimulating material in the Graham and Ritchie's paper (2006), concerning not just disease-classification but also the ethics of diagnosis. My concern is with the way in which they adduce Ian Hacking's views in the philosophy of science in support of their own. The authors (...) quote with approval his "dynamic nominalism" and its influence on Zachar's concept of "practical kinds." Hacking's view, as the authors quote it, is that "People classified in a certain way tend to conform to or grow into the ways that they are described; but they also evolve in their own ways, so that the classifications and descriptions have to be constantly revised" (1995, 21). The act of classifying changes both the classifier and the subject of classification, resulting in facts and categories that are both socially created and real. Hacking calls this "the looping effect of human kinds," and comments that "Multiple personality [disorder] is an almost too perfect illustration of this feedback effect" (1995, 21). The authors comment that Zachar (2000) builds on Hacking's position, discarding essentialist notions of classification that are limited to inherent biological properties, and turning instead to "practical kinds—nonarbitrary cultural artifacts intended to meet pragmatic needs (e.g. therapeutic, predictive prognostic, labeling effects, and physiology)" (Graham and Ritchie 2006, 36). Practical kinds, they believe, offer a way out of the clinical approach focused on mild cognitive impairment (MCI) as a precursor to, or mild form of, Alzheimer's disease. The inclination of the authors, as I read them, is to treat MCI as a practical or human kind, and not, like Alzheimer's disease, as a natural kind.My concern is whether the "looping effect of human kinds" can be transferred to the case of MCI from Hacking's original case study in Rewriting the Soul, multiple personality disorder (MPD). Hacking wished there to undermine the traditional debate over whether MPD is a "social or psychiatric artifact." He claims, correctly I think, that the presupposition behind the question "Is MPD a real disorder as opposed to a product of social circumstances?" should be rejected. The fact that a disorder is a product of social circumstances does not make it less real (1995, 12). On the looping of human kinds, Hacking comments that "The concept of child abuse [implicated in MPD] may itself be so made and molded by attempts at knowledge and intervention, and social reaction to these studies, that there is no stable object, child abuse, to have knowledge about." This is a "no fact of the matter" response, and it [End Page 51] is based on the recognition of conceptual change. He later adds that child abuse "is a real evil, and it was so before the concept was constructed. It was nevertheless constructed. Neither reality nor construction should be in question" (1995, 61, 68). However, Hacking's conclusions about the reality of MPD express only a muted skepticism. Utilitarian skeptics approach this question by asking, "What is the most effective treatment?" Hacking writes that "in their hearts [such skeptics] suspect that the outcome of multiple therapy [therapy that condones or even encourages the development of multiples in the patient] is a type of false consciousness" (1995, 267). The skeptics about MPD are making a moral judgment, he believes; but on whether that moral judgment is correct, he is silent, although the suspicion must be that he agrees with it.How do these considerations apply to the case of MCI? Graham and Ritchie rightly note that classifying a subject as suffering from MCI, and informing them of the diagnosis, will affect them adversely—it will cause suffering not least because there is at present no cure. However, it must surely be conceded that any disease at all—physical or mental—is a social entity insofar as it involves behavioral ascriptions to the subject concerning their incapacity. The authors also note the vested interests—especially from the pharmaceutical industry—in developing a diagnostic category of MCI. These interests are present in the development of any significant diagnostic... (shrink)

Background: In the present study, we aimed to better investigate attention system profile of Parkinson's disease-Mild Cognitive Impairment patients and to determine if specific attentional deficits are associated with 123I-FP-CIT SPECT.Methods: A total of 44 de novo drug-naïve PD patients [ with normal cognition and 17 with MCI ], 23 MCI patients and 23 individuals with subjective cognitive impairment were recruited at the Clinical Neurology Unit of Santa Chiara hospital. They were assessed by a wide neuropsychological (...) battery, including Visual Search Test measuring selective attention. Performances among groups were compared by non-parametric tests. Further, Spearman's rank correlations were performed to explore the association between neuropsychological variables and 123I-FP-CIT SPECT data in PD subgroup.Results: PD-MCI patients performed worse on VST than patients with PD-NC, patients with MCI and individuals with SCI. The performance of PD-MCI patients on VST significantly correlated with caudate nucleus 123I-FP-CIT SPECT uptake, whereas a negative correlation between such test and 123I-FP-CIT SPECT uptake in the left putamen was found in PD-NC patients.Conclusions: We suggest that selective attention deficit might be a trigger of cognitive decay in de novo PD-MCI patients. The VST should be routinely used to detect attentional deficits in hospital clinical practice, in the light of its closely association with dopamine depletion of basal ganglia in mildly impaired PD patients. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Mild Cognitive Impairment:Kinds, Ethics, and Market ForcesStephen Ticehurst (bio)KeywordsAlzheimer’s disease, dementia, human kinds, mild cognitive impairment, natural kindsIn their article, Graham and Ritchie (2006) robustly confront the term mild cognitive impairment (MCI). They contrast a "real" diagnosis of Alzheimer's disease (AD) with a potentially spurious human invention called MCI. They argue we should not push MCI and AD too close together, lest MCI (...) catch too much of the reflected reality it does not deserve. I agree with their purpose, but suspect their argument is not as clear cut as we might hope.Classification is fundamental to the human activity called science. It is reflected also in the way we allocate and refine words. Classification allows us to determine the usefulness of terms, to share meaning, and hopefully to predict. MCI is an attempt at classification in this manner.The first problem is the clarity of definition. Graham and Ritchie imply that others see MCI as a precursor to dementia. At times they fall prey to this belief themselves. But is this what MCI claims? This link to AD and its recursive coloring of MCI is central to their argument. It seems that many hope that MCI is a term for "at risk of dementia." This confusion hampers much of the debate. The current operationally defined nosological criteria specify MCI is not dementia. This means that MCI can not be dementia without changing the criteria for one or both. At present, the evidence does not support this. Those people with MCI who will go on to develop dementia cannot reliably be distinguished from those who have a defective memory for other reasons. In the meantime, the link between MCI and dementia of various types is a valid area for investigation. Graham and Ritchie should have more confidence that usefulness can be determined by science and that this will triumph in the end.Modern psychiatry is very keen to believe it is naturalistic. Everything can be measured and will soon be explained by physical laws. However, Graham and Ritchie point to the intrusion of human concepts and values that may be shaping the way we measure the natural world. They invoke the term human kind to differentiate this activity from natural kinds. Psychiatry has always struggled to connect its diagnoses to naturalistic ideas of pathology and etiology. It could be argued that psychiatric nosology has always been susceptible to the creations of humans. Another modern invention—early psychosis—has parallels with the MCI story. But as the Rorschach test shows, most of us continue to see shapes in what really [End Page 53] is only an inkblot. If the shape is something we really want to see, expect, or have been trained to look for, so much the better. A definable precursor state to dementia (or schizophrenia) would make us all happy, not just those insatiable shareholders. However, the earlier in the unfolding of degenerative dementia we go, the less reliable and valid are our clinical diagnoses.Graham and Ritchie say MCI is a human kind, unlike Alzheimer's disease, which is an essential natural kind. The authors argue that the purported relationship between MCI and AD feed back in a loop to give MCI a natural kind standing that it does not yet deserve. They examine the underlying social processes that support this firming of an as yet insubstantial concept. These include the desire for patients and their doctors to have hope and pharmaceutical companies to have markets and profits. They invoke a mythical authorized person who can determine a diagnosis as a newly formed kind after a common act of recognition. Using kind in this context appears to refer to a thing rather than a term. But it is the term that is being socially validated, not the thing. AD is a more socially validated term than MCI, but its relationship with reality remains humanly constructed.Does the invocation of kinds aid this argument? A kind is not really what it appears. A kind is a term to describe a concept that humans hold about the world. Therefore, dividing kinds into various types, such as natural, human, and practical, betrays the inevitable human... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Ambiguities of Mild Cognitive ImpairmentTim Thornton (bio)Keywordsclassification, disease, mild cognitive impairment, normative, valuesCorner and Bond's paper (2006) raises some key ethical questions about the classification and diagnosis of mild cognitive impairment (MCI). In this commentary, I wish to revise some of the general issues about the classification of mental disorder raised by this particular classificatory concept. The central issue raised is the connection (...) between the pathologic status of a condition and what I term the plain facts about the frequency and nature of its symptoms.There are a number of ethical questions raised by applying the label of MCI. Centrally, perhaps, is the concern, illustrated by the case vignettes, that a diagnosis carries negative repercussions that might outweigh the more narrowly medical advantages of an early diagnosis. But although that concern may be appropriate, such ethical complications are a danger of any psychiatric classification or diagnosis, even the most well grounded. Any psychiatric diagnosis can carry a danger of stigma, for example.What seems to make such ethical concerns more serious in this case—at least to a philosopher outsider—is the implicit further concern that MCI is not a real, objective, or, to use a more medical term, valid category or classification. If it is not valid, then any negative connotations of the diagnosis will not be outweighed by medical technological achievements. In other words, the further ethical issues are given much greater weight if the question of validity is not satisfactorily resolved.The question of the reality, objectivity, or validity of MCI can be divided into two issues:1. Is MCI a real, objective, or valid feature of psychological phenomenology?2. Is MCI a real, objective, or valid psychological illness, disease, or pathology?A condition might be a real, objective, or valid feature of psychological phenomenology without being a real illness. It might be some other aspect of human living. Szasz (1960) suggests that this is the case with mental illness (he might more properly say "so-called mental illness") as a whole. But, less controversially, the unusual ability to calculate, mentally and in a flash, the date of future Easter Sundays is a genuine feature of human living—some people possess the ability even if most do not—without either it, or its lack, being an illness. Being real as an illness is a very specific kind of being. It is this, I suggest, that raises difficulties in the case of MCI by contrast with the easier question of whether something is a genuine feature of human living in some other way. [End Page 21]From "normal" and "normative" to "correct" and "incorrect"Corner and Bond (2006) usefully suggest that the question of whether MCI is real is made more difficult by an ambiguity in the sense of the word normal. They suggest that although "physiologic and cognitive decline is assumed to be a normal experience" this still leaves "boundary problems" about "distinguishing normal aging from disease" (Corner and Bond 2006, 3–4). Thus, if the symptoms of MCI are continuous with the ordinary phenomena of physiologic and cognitive decline, then they might also be merely normal. But this does not settle the status of MCI because normal can mean either "normative, that is, usual; or it can mean nonpathologic" (Corner and Bond 2006, 4).On the assumption that MCI is at least continuous with phenomena that are normal, then its symptoms might be normal in the sense of usual but nevertheless pathologic: an inevitable illness. Or they might be usual and nonpathologic, that is, merely a feature of aging that, although regrettable, lacks the connotations of illness (e.g., the appropriateness, if not the possibility, of treatment). (In principle on the assumption in play—that the symptoms of MCI are normal—they might be unusual but nonpathologic akin, for example, to an improved ability to solve crosswords with age that might affect a small lucky proportion of the population. Perhaps such a crossword puzzler might be reassured by their doctor: "Well that is very unusual but there is no need to worry: it is not a symptom of any illness. You are perfectly normal.")Thus the question "Is MCI normal... (shrink)

BackgroundThe cognitive outcomes induced by subthalamic nucleus deep brain stimulation (STN-DBS) remain unclear, especially in PD patients with mild cognitive impairment (MCI). This study explored the cognitive effects of STN-DBS in PD patients with MCI.MethodsThis was a retrospective cohort study that included 126 PD patients who underwent STN-DBS; all patients completed cognitive and motor assessments before and at least 6 months after surgery. Cognitive changes were mainly evaluated by the Montreal cognitive assessment (MoCA) scale and the seven specific (...) MoCA domains, including visuospatial/executive function, naming, attention, language, abstract, delayed recall, and orientation. Motor improvement was evaluated by the UPDRS-III. Cognitive changes and motor improvements were compared between PD-MCI and normal cognitive (NC) patients. Logistic regression analyses were performed to explore predictors of post-operative cognitive change.ResultsAt the time of surgery, 61.90% of the included PD patients had MCI. Compared with the PD-MCI group, the PD-NC group had a significantly higher proportion of cases with post-operative cognitive decline during follow-up of up to 36 months (mean 17.34 ± 10.61 months), mainly including in global cognitive function, visuospatial/executive function and attention. Covariate-adjusted binary logistic regression analyses showed that pre-operative global cognitive status was an independent variable for post-operative cognitive decline. We also found that pre-operative cognitive specific function could predict its own decline after STN-DBS, except for the naming and orientation domains.ConclusionPD-MCI patients are at a lower risk of cognitive decline after STN-DBS compared with PD-NC patients. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reifying Relevance in Mild Cognitive Impairment:An Appeal for Care and CautionJanice E. Graham (bio) and Karen Ritchie (bio)KeywordsAlzheimer’s disease, construction, dementia, market forces, mild cognitive impairmentWe thank the reviewers for their thoughtful comments that probe shadowy areas in our argument, and we welcome this opportunity to elucidate our position. First, we are not repudiating the natural and social facts of pathologic brain degeneration and the physical (...) and cognitive impairments that manifest in people affected by dementia disorders. We are, however, questioning the epistemology, politics, and persistence by some to harden the construct of mild cognitive impairment (MCI) prematurely as a "natural" precursor to dementia. We suggested insufficiencies in viewing MCI as prodromal to Alzheimer's disease (AD; Graham and Ritchie 2006, 36), and pointed to evidence for the prognostic irrelevance of some MCI subcategories (35). The commentators have read our manuscript as suggesting that AD and MCI are different kinds, and that a diagnosis of AD is more "real" than that of MCI. But AD is also fraught with classification issues, as we describe in the section of our paper that deals with consensus committees, published practice guidelines, and the determination of treatment efficacy. Like MCI, AD is a heterogeneous condition, but unlike MCI, AD is a constructed practical kind that does some "work" beyond essentialist (neural degeneration, brain atrophy) claims. Its criteria identify people with well-defined dementia symptoms and multiple cognitive and functional impairments who are in need of, and benefit from, support. Even with these criteria, however, there have been great attempts to achieve definitional accuracy in dementia diagnoses. Practical refinements to the differential diagnosis of dementia based on solid research evidence have made way for more specific recognitions of vascular dementias, dementia of the Lewy body type, and other subtypes beyond AD. So AD too has been subject to more careful, more cautious operationalization in recent years, with research supporting multiple factors and the comorbidity of several types (kinds) of dementia in any one individual.Our paper takes up concerns that are not resolved for dementia and suggests that the nascent category of MCI is still so insufficiently defined as to be ambiguous, and as such, is in danger of identifying individuals with what will be, and has [End Page 57] already been, linked to a debilitating and deeply stigmatizing and fatal disorder (AD). We are not contesting the reality that some people begin to display early signs of cognitive loss, nor are we suggesting that symptoms be ignored; as researchers, we stand behind the careful tracking of symptoms and signs in patients and research participants as an essential clinical and research practice. In a era where the public has been made wary of the potentially fatal effects of new treatments whose more careful scrutiny in specific populations would have saved lives (e.g., Fontanarosa, Rennie, and DeAngelis 2004; Psaty and Furberg 2005), and made all the more popular by what Kramer coined "diagnostic bracket creep" (1993, 15), we are questioning the drivers and value of a premature diagnostic classification whose definitional accuracy is neither sufficient nor effective for specific identification of individuals.That matters of fact are constructed does not take away from their natural fact. Some people have subjective reports or show objective evidence of cognitive decline while having preserved activities of daily living—the construction of this evidence indicates they are not normal and they are not demented. Based on such evidence, where then does the balance of probability for MCI lie? A multidisciplinary international group of experts gathered in Stockholm in 2003 to discuss MCI concepts (Winblad et al. 2004). They acknowledged that the heterogeneous etiology of MCI contributes to "some confusion concerning the specific boundaries of the condition", stating that this "not normal, not demented" condition is nonetheless "useful both clinically and as a research entity" (p. 241). Importantly, they concluded that MCI needs "better definition" (p. 246). It was at this stage that we first wrote our manuscript, and in the subsequent two years we have eagerly awaited new studies, and the recognition of flexible, practical subtypes to evolve.We state "that MCI cannot be considered to be a separate clinical entity" (Graham and... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Alzheimer's Disease, Mild Cognitive Impairment, and the Biology of Intrinsic AgingThomas B. L. Kirkwood (bio)Keywordsaging, Alzheimer’s disease, genetic mutation, mild cognitive impairment, telomereThe article by Gaines and Whitehouse (2006) raises key questions about the uncertain relationship between (i) the intrinsic, "normal" aging process, and (ii) the clinicopathologic states represented by the labels of Alzheimer's disease (AD) and mild cognitive impairment (MCI). This short (...) commentary offers a perspective on this debate that is drawn from a consideration of underlying biological mechanisms.Because age is unquestionably the greatest single risk factor associated with AD and MCI, I begin by asking what we know about the intrinsic processes of aging. The central feature of current understanding of intrinsic aging is that it consists of the gradual, lifelong accumulation of a wide variety of molecular and cellular faults that begins very early in life and eventually leads to overt functional impairments resulting in age-related frailty, disability, and disease (Kirkwood 2005). This is an essentially bottom-up process. A strong consensus has emerged in recent years that there is no active program for aging and that there are no genetic factors that have evolved specifically to cause aging or age-related diseases. Unquestionably, there are genes that influence susceptibility to disease and even length of life, but these genes are genes for maintenance and repair functions, not for aging. It is the limitation in the past evolutionary pressure to invest in greater longevity than was required, within an environment where life was usually truncated by hazards such as starvation, injury, or infection, that means that our maintenance systems—good as they are—are insufficient to keep us going indefinitely. Added to this is the idea that there are probably also genes that program processes that are good for the young organism, but which may in later life have harmful effects. Processes like inflammation and apoptosis, which are seen to occur extensively in aged tissues, including brain, surely evolved to help cope with infection and cellular damage arising earlier in life. That they are called into play in aged tissues is a direct, but secondary, consequence of accumulated damage.With this general framework to understand the intrinsic biology of aging, let us now ask what we might expect a priori for the aging of an organ such [End Page 79] as the brain. Although we cannot pretend complete ignorance of how the brain actually does age, our enquiry can be based entirely on data from other organ systems, so we can develop our predictions about brain aging without prejudice.Aging begins very early during human development, faults accumulating from the first stages of embryonic development. Each time a cell divides, each of the daughter cells is likely to acquire a few new mutations. We know this from the estimates for the error rate in DNA replication and the size of the human genome. It is confirmed by direct evidence that at individual gene loci where mutations have been measured, mutation frequency increases with age (Morley 1998; Vijg 2000). In addition to replication errors, DNA is damaged on a daily basis to a very considerable degree by agents such as reactive oxygen species (free radicals), which are formed as byproducts of normal cellular metabolism. Although most of this damage is corrected by repair, the repair mechanisms themselves are not error free and additional mutations accumulate through this route. If a mutation is lethal to the cell, the cell dies and thus the mutation is eliminated. However, the majority of mutations are nonlethal, either because the mutation is recessive and the cell carries an intact gene copy on the other chromosome, because the gene is not currently required, or because the mutation produces only a delayed deleterious effect. Examples of genes that produce delayed deleterious effects include the genes responsible for familial AD. It is interesting to reflect that on statistical grounds alone, it is almost certain that each of us carries a randomly determined fraction of cells in our brains that bear amyloid precursor protein or presenilin mutations associated with AD. We also carry a heterogeneous array of random mutations that compromise essential cell maintenance functions. How many such... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Introduction:The Heat of Mild Cognitive ImpairmentJulian C. Hughes (bio)Keywordsaging, explanation, mild cognitive impairment, understanding, valuesDebates about mild cognitive impairment (MCI) are generating heat, albeit civilized heat. But under the surface, as I think the papers in this special issue demonstrate, the civilized heat comes from a good deal of passion. One way in which philosophy can contribute to the debate is by making plain (...) the sources of this passion, so that the motivating forces are clearer.One motivating force is this: There will be people who do not have dementia but who have symptoms or signs that might predict dementia, which cause them concern, whom we might help by early intervention. The intervention might involve advice and support, or it might involve some form of drug treatment; and in the utopia of our dreams, it might involve prevention. All of this is very motivating for clinical scientists. It also offers a laudable motivation to pharmaceutical companies, who simultaneously must have regard to the possibility of profits for their shareholders.Here, however, is an alternative motivation: The effects of aging must not be ignored if help can be given, but older people must not be stigmatized by a medical process that thrusts disabling labels on them. People age, but they age differently, and it is better to recognize difference, both from a biological and from a philosophical perspective. Thus, a passionate commitment to the cause of individual agency in old age and a desire for authentic autonomy for older people provide strong motivation too.At root, then, the conflicting passions over MCI reflect the age-old struggle in the philosophy of psychiatry between the natural sciences (Naturwissenschaften) and the human or cultural sciences (Geisteswissenschaften): the tension is between a tendency to approach the problem with the aim of eliciting a scientific explanation and a tendency to try to achieve a human and cultural understanding of the phenomena (Phillips 2004). So, although MCI can be regarded as an explanatory diagnostic entity with some predictive value, it can also be regarded as a label that might cause harm or as a human phenomenon that requires understanding. Furthermore, MCI raises ontological questions about the nature of disease entities. And there is a wider issue as well about how aging itself should be regarded.From a biological perspective, it turns out there is no clear cutoff between what is normal and what [End Page 1] is not. Hence, in a number of ways, values seem to be as important as facts (Sadler 2005). Perhaps philosophy should content itself with saying no more than this: MCI ought not to be considered or debated as if it lies outside the realm of evaluative judgment. The very possibility of its existence as a clinical entity is a matter worthy of moral and social discourse.The direction of thought indicated here and in the papers that follow, however, is more radical than the easily won point that the "diagnosis" of MCI is not value free. On the back of the biological point, that there is a continuum between physiological and pathological aging, is the broader philosophical point that aging can neither be understood solely in terms of physiology nor in terms of pathology, nor even in terms of both. Ageing represents, inter alia, a social and cultural phenomenon manifest in the context of particular psychological and spiritual responses to a mixture of physiological adaptations and pathological predispositions. Without the broader picture, we tend to characterize old age, as Michael Bavidge has suggested elsewhere, in terms of deteriorations: "We should think of old age as offering alternative rather than impaired ways of experiencing life" (2006, 49). The difficulty is that any diagnosis seems to suggest impairment in one form or another. The radical suggestion, therefore, might be to commend descriptions that encourage shared understanding over and above the giving of names and labels.In a brief critique of the scientific approach to "banal memory disorders and MCI", Jean-Marie Léger, like Bavidge, regrets the extent to which people with cognitive impairment "are described in terms of what they have lost, with no regard for the wealth of faculties which are still present." Léger... (shrink)

Elucidating distinct morphological atrophy patterns of Alzheimer’s disease and its prodromal stage, namely, mild cognitive impairment helps to improve early diagnosis and medical intervention of AD. On that account, we aimed to obtain distinct patterns of voxel-wise morphological atrophy and its further perturbation on structural covariance network in AD and MCI compared with healthy controls. T1-weighted anatomical images of matched AD, MCI, and HCs were included in this study. Gray matter volume was obtained using voxel-based morphometry and compared (...) among three groups. In addition, structural covariance network of identified brain regions exhibiting morphological difference was constructed and compared between pairs of three groups. Thus, patients with AD have a reduced hippocampal volume and an increased rate of atrophy compared with MCI and HCs. MCI exhibited a decreased trend in bilateral hippocampal volume compared with HCs and the accelerated right hippocampal atrophy rate than HCs. In AD, the hippocampus further exhibited increased structural covariance connected to reward related brain regions, including the anterior cingulate cortex, the putamen, the caudate, and the insula compared with HCs. In addition, the patients with AD exhibited increased structural covariance of left hippocampus with the bilateral insula, the inferior frontal gyrus, the superior temporal gyrus, and the cerebellum than MCI. These results reveal distinct patterns of morphological atrophy in AD and MCI, providing new insights into pathology of AD. (shrink)

ObjectiveThis study aimed to develop a diagnostic model of multi-kinematic parameters for patients with amnestic mild cognitive impairment (aMCI).MethodIn this cross-sectional study, 94 older adults were included (33 cognitively normal, CN; and 61 aMCI). We conducted neuropsychological battery tests, such as global cognition and cognitive domains, and collected gait parameters by an inertial-sensor gait analysis system. Multivariable regression models were used to identify the potential diagnostic variables for aMCI. Receiver operating characteristic (ROC) curves were applied to assess (...) the diagnostic accuracy of kinematic parameters in discriminating aMCI from healthy subjects.ResultsMultivariable regression showed that multi-kinematic parameters were the potential diagnostic variables for aMCI. The multi-kinematic parameter model, developed using Timed Up and Go (TUG) time, stride length, toe-off/heel stride angles, one-leg standing (OLS) time, and braking force, showed areas under ROC (AUC), 0.96 [95% confidence interval (CI), 0.905–0.857]; sensitivity, 0.90; and specificity, 0.91. In contrast, a single kinematic parameter’s sensitivity was 0.26–0.95 and specificity was 0.21–0.90. Notably, the separating capacity of multi-kinematic parameters was highly similar to Montreal Cognitive Assessment (MoCA; AUC: 0.96 vs. 0.95). Compared to cognitive domain tests, the separating ability was comparable to Auditory Verbal Learning Test (AVLT) and Boston Naming Test (BNT; AUC: 0.96 vs. 0.97; AUC: 0.96 vs. 0.94).ConclusionWe developed one diagnostic model of multi-kinematic parameters for patients with aMCI in Foshan. (shrink)

Start Exercising Your Brain Now: 201 Word and Number Exercises to Challenge Your Memory, Reasoning, Visual-Spatial Skills, Vocabulary, and More! Keep your brain active, even with MCI. For adults with Mild Cognitive Impairment, brain exercises are the best way to stay sharp and delay the onset of dementia. That’s why cognitive specialist Dr. Tonia Vojtkofsky tailored this fun workbook specifically for people with MCI. It’s the first of its kind! Find a word that meets the definition and contains (...) the letters “CAN” Truthful; straightforward; frank A brown nut with an edible kernel A cylinder black of wax with a wick Pick the one statement that is correct: UWYVX V is right of X. W is right of V. V is between U and Y. Y is right of W. Find and complete the pattern: 5, 8, 12, 17, 23, _____, _____, _____, _____. 14, 56, 224, 896, _____, _____, _____, _____. 5, 15, 30, 90, 180 _____, _____, _____, _____. Plus: Complete the word, image recall, determine the order, matching, true or false, logic problems, decode using clues, trivia, discover the pattern, word mazes, and math games. “The idea for the book originated from my need to provide appropriate brain exercises for my clients who have MCI. All of the brain-exercise books on the market today are for people with no cognitive impairment and therefore were too hard for my clients. I knew that I had to provide something for this underserved population.”—Dr. Tonia Vojtkofsky. (shrink)

Music-based interventions (MBI) have become increasingly widely adopted for dementia and related disorders. Previous research shows that music engages reward-related regions through functional connectivity with the auditory system, but evidence for the effectiveness of MBI is mixed in older adults with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). This underscores the need for a unified mechanistic understanding to motivate MBIs. The main objective of the present study is to characterize the intrinsic connectivity of the auditory and reward (...) systems in healthy aging individuals with MCI, and those with AD. Using resting-state fMRI data from the Alzheimer’s Database Neuroimaging Initiative, we tested resting-state functional connectivity within and between auditory and reward systems in older adults with MCI, AD, and age-matched healthy controls (N = 105). Seed-based correlations were assessed from regions of interest (ROIs) in the auditory network (i.e., anterior superior temporal gyrus, posterior superior temporal gyrus, Heschl’s Gyrus), and the reward network (i.e., nucleus accumbens, caudate, putamen, and orbitofrontal cortex). AD individuals were lower in both within-network and between-network functional connectivity in the auditory network and reward networks compared to MCI and controls. Furthermore, graph theory analyses showed that the MCI group had higher clustering and local efficiency than both AD and control groups, whereas AD individuals had lo... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Demystifying the Mystery of Alzheimer's as Late, No Longer Mild Cognitive ImpairmentPeter J. Whitehouse (bio)Keywordsaging, Alzheimer’s disease, deconstruction, mild cognitive impairmentProfessor Tom Kirkwood and Michael Bavidge's comments are welcome additions to our discourse as both emphasize the importance of considering mild cognitive impairment (MCI) and Alzheimer's disease (AD) in relationship to the normal biological and cultural processes of aging. Whereas I agree with my colleague (...) and co-author, Atwood Gaines' response, I wish to add my own commentary to update the reader concerning the dynamic political processes at work in the social construction and deconstruction of MCI and AD. I have referred to MCI as autodeconstructing AD because whatever we come to think of the MCI label on the spectrum of cognitive aging should alter our beliefs about the ultimate utility of the concept of AD. Tensions in the field of study of MCI have increased since the project reported in this journal began. The social science and philosophical contributions toward understanding MCI need to inform our debate now; otherwise, we will be less effective at influencing a critical debate for society about its relationships to medicine, science, and modern capitalism.This past year, Ron Petersen, the major proponent of the concept of MCI was awarded the prestigious Potamkin Prize for research in Alzheimer's disease by the American Academy of Neurology. The National Institute on Aging (NIA) placed the discovery of MCI as first on the list of contributions during twenty years of research funded through hundreds of millions of dollars poured into the NIA Alzheimer's Research Centers. Some have even suggested that we relabel MCI of the amnestic type, Petersen syndrome. Yet, John Morris, who was co-awarded the Potamkin Prize, has continued to write that MCI is early AD and most recently has suggested (Morris 2006) that we should revise our diagnostic criteria. He joins me and a growing list of other so-called thought leaders who believe (but do not always state publicly) that the term MCI is not useful clinically. Lon Schneider (2005) has recently joined the camp of critics publicly by suggesting that MCI is [End Page 87] not only confusing clinically but is now possibly retarding research.The proliferation of different kinds of MCI indicates that we are studying heterogeneous processes of brain aging. Whereas, John Morris suggests that we relabel MCI as early AD, I have suggested the converse. For example, in a grand rounds lecture at Johns Hopkins in March 2004, I used the lecture title "LNLMCI (late no longer MCI)" as a synonym for AD.Kirkwood is right to compare the quest for biological therapy for AD to the search to treat aging processes in other organs. He has been an outspoken critic of anti-aging medicine quackery that claims that aging itself is a disease that can be reversed today. But, if AD is brain aging, are we not in fact creating a "disease" category that raises false hopes and expectations?Kirkwood also points out that aging is a lifespan process. To prevent dementia in older individuals, we should prevent damage to neurons in younger individuals. Recently, it has been claimed, for example, that exposure to lead in young animals makes these animals more at risk for amyloid deposition in later life (Basha et al. 2005). Whether or not lead directly affects the pathogenesis of AD, it seems eminently reasonable to try to prevent damage to neurons in young children so that they may have maximum cognitive capacity throughout their lifespan.Almost ten years ago, when I stepped down as the editor of the Alzheimer's Disease and Associated Disorders Journal and as John Morris took over this responsibility, I wrote an editorial calling for the end of AD (Whitehouse 2001). In other words, I argued that thinking through the invention of the term mild cognitive impairment reveals that we are attempting to assign medical categories to what are a heterogeneous set of processes that affect our brains as we age. At the hundredth anniversary of the first case of what we have come to call Alzheimer's disease, perhaps it is time to reflect on the individual and social... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Under the Floorboards:Examining the Foundations of Mild Cognitive ImpairmentMichael Bavidge (bio)KeywordsAlzheimer’s disease, culture, dementia, normal aging, science"Building a mystery: Alzheimer disease, mild cognitive impairment, and beyond" (Gaines and Whitehouse 2006) is an absorbing and important case study of how Alzheimer's disease (AD) came to be seen as a disease and how mild cognitive impairment (MCI) has been constructed in recent years as a related (...) incipient condition.The interdisciplinary approach taken in the article produces findings of very different sorts, which are then marshaled to challenge the status of AD and MCI. The factors identified as contributing to the emergence of dementia as a disease include the inconclusive nature of the empirical evidence relating to the causes of dementia, the divergence in the paradigms of the biological sciences, the social pressures resulting from the aging of the population, consumerism in medicine, research funding, the profit motive in the pharmaceutical industries, and our "hypercognitive culture."There is a danger in a short article drawing on detailed work in different disciplines that no single argument is conclusive and the combination of inconclusive arguments remains unsatisfactory. Nevertheless, the picture that emerges is convincing. It is interesting to follow the details of a particular case history to track the intricate interlacing of clinical findings and social decision making that enter into the construction of a disease. The article traces the factors that encouraged the identification of dementia as a widespread, treatable condition and the diagnostic techniques and treatments that determined the delineation of the disease.In the case of AD and MCI, the implications of this process of construction extend beyond taxonomy. They call into question our attitude to aging. Do we see aging as itself a pathology? When Professor Tom Kirkwood writes "from a biological point of view, there is nothing necessary or inevitable about aging" (2001, xi), he does not mean to deny that as the years pass people get older (inevitably); he means that the deteriorations that at present we cannot but see as normal features of aging, are not inevitable. Do we have a spurious ideal of competence based on a time-slice taken from what we like to think of the prime of our lives? Why do we not think of the "cognitive [End Page 75] impairments" of childhood and adolescence as pathological? These are fundamental questions about our experience and understanding of living, aging and dying and they add layers of significance to the topic of the paper (Bavidge 2006).The main focus of the article is to expose the complex process involved in the classification of dementia as "a degenerative, biological, clinical entity" (Gaines and Whitehouse 2006, XX) and to raise doubts about its distinction from normal aging. Not everyone will be happy that so much weight is placed on disease as a dysfunctional clinical entity. Nor will everyone think that so much hangs on the disease status of dementia and MCI. However, on any account, the contrast between disease and normal aging has become less clear because our understanding of both terms of the comparison has become less secure. The question "Is dementia a disease?" is matched by the question "Is aging normal?"Many of the disabilities or degenerations associated with aging are now understood to be conditions that could be avoided, cured, or controlled. So although the article raises doubts about the stability of the category of AD, parallel problems have arisen about normal aging. If important elements of what we classify as dementia should be seen as normal human development, it is equally the case that some aspects of what we accept as part of the normal aging experience should be seen as pathological. The authors assert "we have not argued that there is no 'there' there. Rather, we suggest that the mystery of the 'there' (i.e., AD, MCI) may not be much different (if at all) from, and probably is, the mystery of the 'everywhere' (i.e., aging)" (Gaines and Whitehouse 2006, 61).The article is an exercise in the sociology of knowledge. This will be enough in itself to raise some hackles. It is interesting how an historical and sociological approach to the sciences has... (shrink)

Definitions of the concept of mild cognitive impairment (MCI) and suggested therapies are controversial. There are no widely acknowledged therapies and the ethical implications and methodologic issues around identifying and defining people with MCI are important concerns. The psychosocial implications for the person being labeled as having MCI have not been widely explored. This paper addresses these issues and presents data from two contrasting case studies. Key analytical themes identified in the qualitative analysis include different views about the (...) causes of dementia ("normal aging" versus disease); fear and anxiety about dementia; how such factors influence presentation to health professionals; and the effect of a label of cognitive impairment on quality of life. Our conclusion is that the usefulness and justification for early identification of cognitive impairment in a situation that has not yet been recognized by those involved should be questioned. (shrink)

Apathy and depression are frequently observed as behavioral and psychological symptoms of dementia, respectively, and are important for ensuring adequate care. This study aims to explore effective non-pharmacological interventions for apathy and depression with mild cognitive impairment and dementia. Five search engines including PubMed, Scopus, CINAHL, PsycInfo, and Web of Science were used to extract relevant studies. Inclusion criteria were studies that involved participants who were diagnosed with MCI or dementia, included quantitative assessments of each symptom, and employed (...) randomized controlled trials. Twenty studies were extracted, with interventions have been conducted in care facilities, the community, and hospitals. Participants in many studies had MCI or mild-to-moderate dementia but were not diagnosed with the subtypes of dementia. Few studies had set apathy and depression as the primary outcomes of non-pharmacological interventions. The findings suggested that emotional and stimulation-oriented approaches to apathy and depression would be useful for people with MCI or mild-to-moderate dementia. It would be helpful for therapists to assess the clinical features of the target symptoms for selecting suitable interventions. Additionally, increasing the number of randomized controlled trials focusing on apathy or depression as primary outcomes would offer a more definite conclusion for future systematic reviews. (shrink)

The purpose of this study was to investigate emotion recognition and processing in patients with mild cognitive impairment in order to update the state of current literature on this important but undervalued topic. We identified 15 papers published between 2012 and 2022 that meet the inclusion criteria. Paper search, selection, and extraction followed the PRISMA guidelines. We used a narrative synthesis approach in order to report a summary of the main findings taken from all papers. The results collected (...) are still ambiguous: some studies did not find any differences between MCI and healthy controls groups in emotion recognition and processing, and other results reported emotion-specific deficits in emotion recognition regarding MCI patients. It is essential to underline that these findings could not be generalized to the whole MCI population due to the heterogeneous use of measures and composition of the sample. This does not allow us to make a comprehensive comparison between the results. Our suggestion for future research is to align the results using the same type of tests and emotion recognition assessment. (shrink)

The Test Your Memory is a brief self-administered, cognitive screening test, currently used in several settings. It requires minimal administrator supervision and the computation of the final test score takes approximately 2 min. We assessed the discrimination ability of the Italian version of the TYM in detecting Mild Cognitive Impairment in clinical setting. TYM-I was administered to 94 MCI patients and 134 healthy controls. The clinical diagnosis of MCI was considered as the gold standard. An extended formal neuropsychological (...) test battery was used to define MCI subtypes. Receiver Operating Characteristic analyses were conducted to find the optimal cut-off and measure discrimination ability of TYM-I in detecting MCI. TYM-I had a similar area under the curve point estimate as Mini Mental State Examination. A TYM-I score lower or equal to 36 was found to be optimal cut off to detect MCI. The TYM-I showed the highest discrimination ability among individuals aged more than 70 and high educational level. The amnestic MCI subtype patients, compared to non-amnestic MCI patients, had worse performance in recall, orientation and visuospatial abilities TYM-I subscores. The TYM-I is a valid screening test in detecting cognitive dysfunction, easily carried out in clinical practice. The TYM-I subscores may allow to identify amnestic and non-amnestic MCI subtypes. (shrink)

IntroductionThis study aimed to evaluate, in adults with mild cognitive impairment, the brain atrophy that may distinguish between three AT biomarker-based profiles, and to determine its clinical value.MethodsStructural MRI was employed to evaluate the volume and cortical thickness differences in MCI patients with different AT profiles, namely, A−T−−: normal AD biomarkers; A+T−−: AD pathologic change; and A+T++: prodromal AD. Sensitivity and specificity of these changes were also estimated.ResultsAn initial atrophy in medial temporal lobe areas was found in the (...) A+T−− and A+T++ groups, spreading toward the parietal and frontal regions in A+T++ patients. These structural changes allowed distinguishing AT profiles within the AD continuum; however, the profiles and their pattern of neurodegeneration were unsuccessful to determine the current clinical status.ConclusionsMRI is useful in the determination of the specific brain structural changes of AT profiles along the AD continuum, allowing differentiation between MCI adults with or without pathological AD biomarkers. (shrink)

It is unclear whether the decline in executive function and perceptual-motor function found in older adults with mild cognitive impairment is the result of a normal aging process or due to MCI. This study aimed to determine age-related and MCI-related cognitive impairments of the EF and PMF. The EF and PMF were investigated across four groups of 240 participants, 60 in each group, including early adult, middle adult, older adult, and older adult with probable MCI. The EF, working (...) memory, inhibition, and cognitive flexibility were evaluated using digit span backward tasks, the Stroop color-word test, and the modified switching verbal fluency test, respectively. The PMF, visual perception, visuoconstructional reasoning, and perceptual-motor coordination were evaluated using the clock reading test, stick design test, and stick catching test, respectively. Group differences were found for all subdomains of EF and PMF, except for perceptual-motor coordination, indicating that this subdomain could be maintained in older adults and was not affected by MCI. For the age difference, working memory, cognitive flexibility, visual perception, and visuoconstructional reasoning remained stable across middle adults and started to decline in older adults, while cognitive inhibition began to decrease in middle adults and it further declined in older adults. To control the confounding effect of education level, the results showed that only cognitive flexibility was further decreased in older adults with probable MCI compared to those without MCI. In conclusion, cognitive inhibition decreased earlier in middle adults, whereas EF and PMF started to decline in older adults. Cognitive flexibility was the only MCI-sensitive cognitive function. (shrink)

Background: The field of voice and speech analysis has become increasingly popular over the last 10 years, and articles on its use in detecting neurodegenerative diseases have proliferated. Many studies have identified characteristic speech features that can be used to draw an accurate distinction between healthy aging among older people and those with mild cognitive impairment and Alzheimer's disease. Speech analysis has been singled out as a cost-effective and reliable method for detecting the presence of both conditions. In (...) this research, a systematic review was conducted to determine these features and their diagnostic accuracy.Methods: Peer-reviewed literature was located across multiple databases, involving studies that apply new procedures of automatic speech analysis to collect behavioral evidence of linguistic impairments along with their diagnostic accuracy on Alzheimer's disease and mild cognitive impairment. The risk of bias was assessed by using JBI and QUADAS-2 checklists.Results: Thirty-five papers met the inclusion criteria; of these, 11 were descriptive studies that either identified voice features or explored their cognitive correlates, and the rest were diagnostic studies. Overall, the studies were of good quality and presented solid evidence of the usefulness of this technique. The distinctive acoustic and rhythmic features found are gathered. Most studies record a diagnostic accuracy over 88% for Alzheimer's and 80% for mild cognitive impairment.Conclusion: Automatic speech analysis is a promising tool for diagnosing mild cognitive impairment and Alzheimer's disease. The reported features seem to be indicators of the cognitive changes in older people. The specific features and the cognitive changes involved could be the subject of further research. (shrink)

ObjectiveThis study aimed to investigate the morphometric alterations in the cortical and subcortical structures in multiple system atrophy patients with mild cognitive impairment, and to explore the association with cognitive deficits.MethodsA total of 45 MSA patients and 29 healthy controls were recruited. FreeSurfer software was used to analyze cortical thickness, and voxel-based morphometry was used to analyze the gray matter volumes. Cortical thickness and gray matter volume changes were correlated with cognitive scores.ResultsCompared to healthy controls, both MSA subgroups (...) exhibited widespread morphology alterations of brain structures in the fronto-temporal regions. Direct comparison of MSA-MCI and MSA-only patients showed volume reduction in the left superior and middle temporal gyrus, while cortical thinning was found in the left middle and inferior temporal gyrus in MSA-MCI patients. Cortical thinning in the left middle temporal gyrus correlated with cognitive assessment and disease duration.ConclusionStructural changes in the brain occur in MSA-MCI patients. The alteration of brain structure in the left temporal regions might be a biomarker of cognitive decline in MSA-MCI patients. (shrink)

Working memory is developed in one region of the brain called the dorsolateral prefrontal cortex. The dysfunction of this region leads to synaptic neuroplasticity impairment. It has been reported that several biochemical parameters and anthropometric measurements play a vital role in cognition and brain health. This study aimed to investigate the relationships between cognitive function, serum biochemical profile, and anthropometric measurements using DLPFC activation. A cross-sectional study was conducted among 35 older adults who experienced mild cognitive (...) class='Hi'>impairment. For this purpose, we distributed a comprehensive interview-based questionnaire for collecting sociodemographic information from the participants and conducting cognitive tests. Anthropometric values were measured, and fasting blood specimens were collected. We investigated their brain activation using the task-based functional MRI, specifically in the DLPFC region. Positive relationships were observed between brain-derived neurotrophic factor and Mini-Mental State Examination ; however, negative relationships were observed between serum triglyceride and serum malondialdehyde with right DLPFC activation while the participants performed 1-back task after adjustments for age, gender, and years of education. In conclusion, higher serum triglycerides, higher oxidative stress, and lower neurotrophic factor were associated with lower right DLPFC activation among older adults with MCI. A further investigation needs to be carried out to understand the causal-effect mechanisms of the significant parameters and the DLPFC activation so that better intervention strategies can be developed for reducing the risk of irreversible neurodegenerative diseases among older adults with MCI. (shrink)

ObjectivesTo comprehensively determine the effect of dance activities on the cognitive functions and its sub-domains of older adults with mild cognitive impairment.MethodsWe obtained data from PubMed, Web of Science, EBSCO, China national knowledge infrastructure, Wanfang data, and VIP databases from 2017/01/01 to 2022/03/01. We included trials of older adults with MCI that underwent dance activity intervention and fulfilled the inclusion criteria. Two researchers independently assessed the quality of the study using the Cochrane risk of the bias assessment tool. (...) Meta-analysis was performed when data were available, with further subgroup analysis, using Review Manager 5.4, and sensitivity analysis was performed using Stata software 15.1.ResultsSearch terms yielded 183 articles, of which 12 fulfilled the inclusion criteria. This included 7 high-quality studies and 5 medium-quality studies. A total of 820 older adults were analyzed. Results showed that dance activity had beneficial effects for global cognition [SMDMMSE = 0.65, 95% CIMMSE, pMMSE = 0.004; SMDMoCA = 0.87, 95% CIMoCA, pMoCA < 0.0001], memory [SMD = 0.61, 95% CI, p < 0.00001], visuospatial function [SMD = −0.39, 95% CI, p = 0.0002], cognitive flexibility [SMD = −0.31, 95% CI, p = 0.003], attention [SMD = 0.34, 95% CI, p = 0.01], and balance [SMD = 1.25, 95% CI, p = 0.04]. Further subgroup analysis showed that open-skill dance activity was more effective in promoting global cognition in older adults with MCI than closed-skill dance activity because of the different stimulation provided by the two types of dance activities in the brain regions of the older adults. It could be speculated that dance activity improved cognitive function mainly by affecting the microstructure and function of the cingulate tract, hippocampus, cardiovascular function, and other brain areas of older adults with MCI.ConclusionDance activities can significantly improve global cognition, memory, visuospatial function, cognitive flexibility, attention, and balance in older adults with MCI. However, more trials with rigorous study designs are necessary to provide more concrete evidence in the future. (shrink)

ImportancePrevious studies of post-acute COVID-19 syndrome have focused on critical cases with severe disease. However, most cases are mild to moderate in disease severity.ObjectiveWe aimed to examine cognitive outcomes in cases of non-critical, mild-to-moderate COVID-19. Design, Setting, and Participants: In this cross-sectional study, we enrolled 72 adults aged 22 to 65 years in Central Texas who had non-critical, mild-to-moderate COVID-19 infection between 13 January 2021 and 20 April 2021.Main Outcomes and MeasuresWe remotely administered cognitive-behavioral testing to determine (...) the frequency of cognitive impairment and examine demographic, clinical, and psychosocial contributors to impairment.ResultsThe frequency of objective cognitive impairment was 40%. The largest number of participants showed impairment on a measure of executive functioning. Attention and processing speed was more impaired in males. Males endorsed lower adherence to social distancing guidelines, which was in turn associated with cognitive impairment across participants. Younger age was correlated with impairment but was also associated with racial/ethnic minority status and increased psychological symptoms. Moderate COVID-19 severity was associated with attention/processing speed impairment, increased pain, and higher number of COVID-19 symptoms.Conclusion and RelevanceMild or moderate COVID-19 infection may be associated with cognitive impairments, especially in the domain of executive functioning. A subgroup of younger individuals may be more vulnerable to cognitive and psychosocial effects of COVID-19.HighlightsQuestion: How frequent is cognitive impairment among non-critical, mild-to-moderate COVID-19 survivors?FindingsIn this cross-sectional study of 72 adults, 40% demonstrated cognitive impairment, particularly in executive function.MeaningNeurologic sequelae, such as cognitive impairment, may be common following COVID-19 infection. (shrink)

BackgroundMild cognitive impairment is a common neurological disorder. Moxibustion has been shown to be effective in treating MCI, but its therapeutic mechanisms still remain unclear. This study mainly aimed to investigate the modulation effect of moxibustion treatment for patients with MCI by functional magnetic resonance imaging.MethodsA total of 47 patients with MCI and 30 healthy controls participated in resting-state fMRI imaging scans. Patients with MCI were randomly divided into true moxibustion group and sham moxibustion group. The degree centrality approach (...) was applied to distinguish altered brain functions. Correlation analysis was then performed to examine the relationships between the neuroimaging findings and clinical symptoms.ResultsCompared with HCs, patients with MCI mainly showed decreased DC in the left middle frontal cortex and bilateral middle cingulate cortex. After moxibustion treatment, the SHAM group had no significant DC findings, while TRUE group mainly showed significant increased DC in the bilateral MFC and MCC, as well as decreased DC in the left middle occipital cortex. Repeated measures analysis of variance showed significant interactions between the two groups of patients with MCI. In addition, the higher Mini-Mental State Examination score was significantly positively correlated with increased DC in the right MFC and left MCC after moxibustion treatment.ConclusionOur findings demonstrate that the potential value of moxibustion treatment on MCI, which adds new insights into the popular view that moxibustion treatment may slow cognitive decline in patients with MCI. (shrink)

In this paper, we suggest some of the dimensions of the problematic concept of Alzheimer Disease as a natural disease discerned by increasingly sophisticated medical scientific progress. Taking a page from Max Weber concerning unique events, we show some of the conceptual building blocks and social processes that have coalesced into the perception of certain phenomena as abnormalities that are seen as implicated in the development of a degenerative disease distinct from the process of normal, but variable, brain aging. We (...) note some of the decisions and social forces pushing for particular conceptualizations, interpretations, and reifications of brain alterations. In so doing, we suggest that the mystery of the "there" may not be much different from, and probably is, the mystery of the "everywhere". (shrink)