Different MRI findings for normal elderly and very mild Alzheimer's disease in a community: implications for clinical practice the Tajiri Project

To investigate magnetic resonance imaging (MRI) findings of very mild dementia, 485 participants were randomly selected in a community. Three hundred and forty participants were of Clinical Dementia Rating (CDR) 0 (healthy), 113 were of CDR 0.5 (questionable dementia), and 32 were of CDR 1 and 2 (including 20 Alzheimer's disease, AD). Cortical atrophy, white matter lesion, etc., were visually assessed. We found that each part of the brain showed atrophy in older adults for CDR 0. For CDR 0.5, the relationships between MRI findings and age were weaker, and for AD, there were no such relationship. Atrophy related with dementia severity was found to be limited to the lateral and medial temporal lobes. For CDR 0.5, amygdala atrophy was the only finding indicating CDR effect but no age effect. The amygdala or anterior entorhinal atrophy is important for discriminating very mild dementia from normal elderly.     

Another wrinkle in the debate about successful aging: the undervalued concept of resilience and the lived experience of dementia

The concept of "successful aging" is a contested discourse in gerontology. Two conflicting paradigms dominate the discussion: a health promotion activity model, and a model critical of the concept of successful aging. However, this study takes a different perspective and proposes that perhaps we have been striving for the wrong goal. The true quest as we age should not be for successful aging, but our goal should be for resilience, an undervalued and not fully examined concept in aging. Developing resilience is possible for many older adults regardless of social and cultural backgrounds or physical and cognitive impairments, unlike successful aging. This article discusses the concept of resilience from a theoretical resilience framework, applies the framework to a dementia population by providing two in-depth case studies of resilience among people with Alzheimer's disease, and concludes by advocating to move the resilience paradigm more front and center into the gerontological debate on successful aging.     

Driving and Alzheimer's disease

Although most aged people remain safe drivers, a greater risk for crashes due to medical conditions is observed in the elderly. Impairment of important functions for safe driving such as visuospatial skills, attention, memory and judgement are observed in dementia, particularly in Alzheimer's disease. The accident rate increases from 9.4 accidents per million vehicle kilometers traveled for 80 to 85 year-old drivers, but raises to 163.6 for drivers with moderate AD. Patients and their families should be informed that patients with mild dementia related to Alzheimer's disease (stage 1 on the Clinical Dementia Rating, CDR), have a substantially increased rate of traffic accidents and therefore should not drive. But subjects in the pre-dementia phase (stage 0.5 at the CDR, mild cognitive impairment) also pose significant driving safety problems. In most States of the USA, and many European countries, but not in France, law requires regular investigating of driving performance in the elderly.     

轻度认知功能障碍的生物学标志

轻度认知功能障碍是正常衰老和痴呆间的一种过渡状态 ,可分为遗忘型和血管型等亚型 ,其概念和诊断正趋向一致。轻度认知功能障碍老年人和痴呆患者在脑脊液Tau蛋白、Aβ、Aβ前体蛋白、胆碱乙酰转移酶活性和事件相关电位等方面有类似变化。文章总结了轻度认知功能障碍的诊断和部分神经生物学指标。     

Driving cessation in older men with incident dementia

OBJECTIVE: To determine the prevalence and cessation of driving among older men with incident dementia in the Honolulu-Asia Aging Study. DESIGN: Retrospective cohort data from a community-based study of incident dementia. SETTING: The Honolulu Heart Program and the Honolulu-Asia Aging Study. PARTICIPANTS: A total of 643 men who were evaluated for the incidence of Alzheimer's disease or other dementia between the fourth and the fifth examination of the Honolulu Heart Program. MEASUREMENTS: Driving history, diagnosis of dementia, grip strength, walking speed, standing balance test, interviewer's rating of vision status, and the neurologist's notes on mentions of driving behavior from informal interviews with a caregiver or family informant. RESULTS: The prevalence of driving declined dramatically with level of cognitive functioning. Among 162 men evaluated and found to have normal cognitive functioning, 78% still drove, compared with 62% of 287 men with poor cognitive functioning but no clinical dementia, 46% of 96 men with a new diagnosis of very mild dementia (Clinical Dementia Rating = 0.5), and 22% of 98 men with a new diagnosis of mild dementia (CDR = 1). Only one of 23 men diagnosed with moderate or more severe staged incident dementia (CDR > 1) was driving. About 10% of the 59 demented persons still driving relied on co-pilots, and only one driver was reported as involved in a crash according to a review of the neurologists' notes. CONCLUSIONS: Incident dementia is a major cause of driving cessation. Based on these data, we estimate that approximately 4% of male drivers aged 75 years and older nationwide (about 175,000 men) have dementia. This number will increase with the projected growth of drivers aged 75 years and older.     

Deficits in inhibitory processes in normal aging and patients with Alzheimer's disease: a review

Empirical data suggest that inhibitory processing is impaired in normal aging. A decrease in inhibitory processing may also play an important role in the cognitive changes occurring in the early stages of Alzheimer's disease. The comparison of inhibitory deficits in Alzheimer's disease and normal aging emphasizes the need to discriminate quantitative changes in inhibitory functioning from qualitative changes which may be specifically related to the disease process. Inhibitory deficits in normal old adults and patients with Alzheimer's disease, suggest different levels of implication of the inhibitory processes. In the cognitive literature, the construct of inhibition, frequently used, is however difficult to define as it refers to many different phenomena. The question of whether or not inhibitory processes are to be considered as a single unit is challenging, and many authors suppose the existence of several distinct inhibitory mechanisms. A taxonomy of inhibition, based on proposals from Nigg and Soltzfus et al., is proposed to facilitate studies of inhibitory dysfunction. Such approach allows a clarification between inhibition deficits specific to normal aging and to Alzheimer's disease.     

Executive function deficits in normal aging, Alzheimer's disease, and frontotemporal dementia

An increasing number of studies suggest that executive functions are among the first cognitive functions to bear negative effects of normal aging. Executive functions also appear to be early affected in Alzheimer's disease and frontotemporal dementia. This article reviews studies in neuropsychology and experimental cognitive psychology with a focus on normal aging, Alzheimer's disease as well as frontotemporal dementia. Study results suggest that so called executive tasks are not equally impaired by normal ageing or dementia in agreement with the recent theoretical models, which state that a set of distinct elementary mechanisms subserve the executive control of cognitive behavior. These models are therefore particularly relevant to address issues stemming from aging.     

Reporting of dementia on death certificates: a community study.

OBJECTIVE: To determine the extent to which conditions suggesting dementia are reported on death certificates of older adults and to identify the factors associated with reporting of dementia. DESIGN: A prospective epidemiological study in which community-dwelling subjects with and without dementia were identified and followed until death, after which their death certificates were examined. POPULATION: A total of 527 individuals who died during 8 years of follow-up of a population-based cohort of 1422 persons aged 65 and older at study entry. MEASUREMENTS: Demographic; study diagnoses, including Clinical Dementia Rating (CDR) Scale stages and diagnoses of Probable and Possible Alzheimer's disease (AD) by NINCDS-ADRDA criteria; disorders listed on death certificates as immediate, underlying, or contributory causes of death. RESULTS: Of 172 deceased subjects with study diagnoses of dementia, 30.2% had CDR = .5 and 69.8% had CDR > or = 1. Of 168 subjects in which dementia subtype could be diagnosed, Probable AD was diagnosed in 31.0% and Possible AD in 38.7%. On their death certificates, conditions indicating or suggesting dementia were reported in 23.8% of dementias overall; in 1.9% of those with CDR = .5 and 33.3% of those with CDR > or = 1; in 36.5% of those with Probable AD and 21.5% of those with Possible AD. In a multiple logistic regression model, variables associated independently with the reporting of dementia in demented individuals were: higher CDR stage of dementia (odds ratio (OR) 22.6; 95% confidence interval (CI), 2.9-174.7); likely etiology of dementia, Probable AD (OR = 3.5; CI, 1.1-10.6); and place of death, long-term care institution (OR = 3.8; 95% CI, 1.6-9.0). CONCLUSIONS: Although Alzheimer's disease is widely regarded as a leading cause of death, dementias are reported on the death certificates of only a quarter of demented individuals in the population at large. Reporting is more likely in those with more advanced dementia, with Probable Alzheimer's disease, and those who die in long-term care institutions.     

Mild cognitive impairment in older people

CONTEXT: As public awareness of Alzheimer's disease increases, more people are asking for help and advice about memory problems. Memory complaints may be secondary to psychiatric, psychological, and physical conditions and is an almost universal early symptom of dementia. The concept of amnestic mild cognitive impairment attempts to describe those people in whom memory loss is not of such severity to merit a diagnosis of dementia. The importance of this group of people is not just the need to develop interventions which ameliorate individual suffering but that they represent a population at high risk of developing dementia, especially Alzheimer's disease, and are an appropriate target for dementia prevention strategies. STARTING POINT: K Kantarci and colleagues (Dement Geriatr Cogn Disord 2002; 14: 198-207) looked at the diagnostic accuracy of magnetic-resonance hippocampal volumetry and spectroscopy in patients with mild cognitive impairment, in normal older people, and in patients with Alzheimer's disease. Hippocampal volumes and N-acetyl aspartate/creatine spectroscopy were the most sensitive assessments discriminating people with mild cognitive impairment from Alzheimer's disease. Combination assessments were better at discriminating these two groups from normal controls. The histological underpinning of cognitive symptoms in older people has been demonstrated by the Cognitive Function and Ageing study (Lancet 2001; 357: 169-75), which showed that a third of people with no clinical evidence of dementia had histopathological hallmarks of Alzheimer's disease. WHERE NEXT? 25 million people across the world have dementia. Mild cognitive impairment, if a validated concept, represents an opportunity for preventing dementia. As more information becomes available about the cause of Alzheimer's disease and prospects emerge for prevention, identification of predementia states offers considerable scope to reduce the individual and societal cost of the illness. Continued validation of the criteria for mild cognitive impairment and studies of intervention should be a priority. As more evidence becomes available highlighting the relatively arbitrary nature of dementia diagnosis (based largely on interference with activities) and interventions become available for the prevention of dementia, mild cognitive impairment and related conditions will become more important.     

Mild cognitive impairment

Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimer's disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimer's disease and other types of dementia.     

The rate of decline in function in Alzheimer's disease and other dementias

BACKGROUND: Functional impairment over time is a necessary condition for the diagnosis of dementia. Increasingly, it is recognized that rates of decline may not follow a linear progression. This variability may indicate that dementia in Alzheimer's disease represents disease rather than inevitable aging. In order to investigate decline in function in dementia, we developed a model of the rate of decline in functions in Alzheimer's disease and in other dementias in comparison with normal aging. METHODS: Secondary analysis of a cross-sectional, representative sample of Canadians aged 65 and older (N = 2,914) was performed. We calculated a measure identified as an impairment index, defined as the probability of the occurrences of an impairment or disability in a structured clinical examination. RESULTS: The rate of functional decline varies for different diagnostic groups and increases with severity of the disease. The distribution for the rate of decline in dementia is distinct from that in aging without cognitive impairment. In those without cognitive impairment, the distribution is exponential. Elderly persons with dementia of any type showed a log-normal distribution. CONCLUSIONS: The difference in the distributions between aging with and without dementia likely reflects fundamental differences in the processes of decline in functions in the two groups. This suggests that the declines seen in persons with dementia are distinct from normal aging. It also has implications for the testing of antidementia medications, in that modeling treatment effects based on an assumption of linear decline is likely to be flawed.     

The aging mind: vascular health in normal cognitive aging

In spite of the breakneck speed at which understanding of the biological basis of the aging process has evolved, the important determinants of aging and longevity have yet to be uncovered. The preservation of cognitive functioning is an essential component of successful aging, and the ability to distinguish those who maintain cognitive health into advanced age from those who experience cognitive decline may influence public health efforts to prevent or delay the onset of cognitive impairment in old age. There is growing evidence implicating vascular risk factors and related subclinical cerebrovascular damage in cognitive impairment and dementia, but Alzheimer's disease is highly prevalent in older populations, and the role of inflammation in vascular and neurodegenerative processes is poorly understood. There is a growing need to examine the effects of these factors on normal cognitive aging. This brief survey of the literature reviews evidence of the roles of subclinical vascular brain damage and exposure to cerebrovascular risk factors in normal cognitive aging.     

Aboriginal Experiences of Aging and Dementia in a Context of Sociocultural Change: Qualitative Analysis of Key Informant Group Interviews with Aboriginal Seniors

Examining the role of culture and cultural perceptions of aging and dementia in the recognition, diagnosis, and treatment of age-related cognitive impairment remains an understudied area of clinical neuropsychology. This paper describes a qualitative study based on a series of key informant group interviews with an Aboriginal Grandmothers Group in the province of Saskatchewan. Thematic analysis was employed in an exploration of Aboriginal perceptions of normal aging and dementia and an investigation of issues related to the development of culturally appropriate assessment techniques. Three related themes were identified that highlighted Aboriginal experiences of aging, caregiving, and dementia within the healthcare system: (1) cognitive and behavioural changes were perceived as a normal expectation of the aging process and a circular conception of the lifespan was identified, with aging seen as going back “back to the baby stage”, (2) a “big change in culture” was linked by Grandmothers to Aboriginal health, illness (including dementia), and changes in the normal aging process, and (3) the importance of culturally grounded healthcare both related to review of assessment tools, but also within the context of a more general discussion of experiences with the healthcare system. Themes of sociocultural changes leading to lifestyle changes and disruption of the family unit and community caregiving practices, and viewing memory loss and behavioural changes as a normal part of the aging process were consistent with previous work with ethnic minorities. This research points to the need to understand Aboriginal perceptions of aging and dementia in informing appropriate assessment and treatment of age-related cognitive impairment and dementia in Aboriginal seniors.     

Validity of direct assessment of functional status as a tool for measuring Alzheimer's disease severity

OBJECTIVE: to assess the validity of the Direct Assessment of Functional Status (DAFS) performance-based functional scale for the staging of dementia severity by comparing it with established clinical, functional and cognitive scales. PATIENTS AND METHODS: 93 consecutive Alzheimer's disease patients underwent DAFS. Socio-demographic variables, cognitive status (Mini-Mental State Examination; MMSE), global disease severity (Clinical Dementia Rating; CDR), disease duration, physical performance (Physical Performance Test, PPT) and functional status (as reported by the primary caregiver) were also recorded and basic (B) and instrumental (I) activities of daily living (ADL) assessed. RESULTS: a significant correlation was found between DAFS and MMSE (Pearson's r = 0.60; P < 0.01), PPT (r = 0.54; P < 0.01) and CDR (Spearman correlation coefficient: -0.48; P < 0.01). A mild, significant correlation was found between DAFS score and daily function as reported by the primary caregiver (r = -0.30 for BADL and r = - 0.27 for IADL). On multiple regression analysis, only MMSE and PPT were independently associated with the DAFS score, explaining 56% of DAFS total variance. ADL scales did not independently contribute to DAFS variance. A multivariate regression model of the association of DAFS with CDR showed that the association was significant even after adjustment for MMSE and PET, suggesting that DAFS scores provide additional information on dementia severity. CONCLUSION: DAFS is a valid tool for the assessment of dementia severity, capturing cognitive and physical aspects of disability.     

A new hypothesis (concept) of diagnosing Alzheimer's disease

The diagnosis of dementia has proven problematic due to different criteria. Even neuropathological changes are arbitrarily defined. A mathematical model is proposed that may standardize diagnosis of dementia, and Alzheimer's disease was used as an example. The model suggests that there are cognitive decline curves that represent the rate of natural attrition for neurons in the cerebral cortex. In normal aging, each individual will lose neurons along one curve. Individuals with higher brain reserve will start off at a higher percentile. An accelerated loss of neurons (dementia) is depicted as a deviation from the natural cognitive decline curve. This model may differentiate age-related cognitive decline from dementia or preclinical dementia. Furthermore, it may allow dementia to be diagnosed earlier, hence earlier treatment. Comparison of data may be easier and more valid if the diagnosis of dementia is standardized under this model. Advantages and challenges of this concept are further discussed.     

Cognitive functional status of age-confirmed centenarians in a population-based study

The New England Centenarian Study is a population-based study of all centenarians in 8 towns near Boston, MA. Age was confirmed for 43 centenarians all alive on a designated date. To determine prevalence of dementia in centenarians, the authors analyzed neuropsychological, medical, and functional status data for 34 (79%) of the centenarians. Definition of dementia was based on the Consortium to Establish a Registry for Alzheimer's Disease criteria, and a Clinical Dementia Rating (CDR) score was formulated for each participant. Seven (21%) had no dementia (CDR score 0), and an additional 4 (12%) were assigned a CDR score of 0.5, uncertain or deferred diagnosis. The remaining 22 (64%) had at least some degree of dementia. The authors calculated Barthel Index scores to determine ability to perform activities of daily living. There was a statistically significant correlation between CDR scores and Barthel Index scores (r = -0.73). Correlation was strongest for those with no or severe dementia, with the greatest range of function measured among those with moderate dementia.     

Gangver?nderungen als Frühindikator einer Demenz

Gait disorders are more common in dementia than in the context of the physiological aging process. Prevalence of dementia-associated gait disturbances depends on the type of dementia and the severity of cognitive impairment. While in vascular dementia gait abnormalities are often clinically apparent at early disease stages, Alzheimer's disease patients usually have stable gait until late disease stages. With up-to-date 'brain-imaging" methods, it has been demonstrated that people suffering from dementia are more dependent on cortical activity in order to maintain gait stability in complex situations. When dysfunction of the frontal or temporal lobes occurs, allocation of these resources may no longer be sufficient. Dual-task paradigms are useful to test such resources. It has been shown in early Alzheimer's disease patients that, if the demand of attention exceeds available capacities, quantitative gait changes occur. Relevant parameters seem to be, e.g., walking speed and stride-time variability. Quantitative assessment of gait dysfunction in dementia may, thus, have the potential to serve as a trait marker.     

Normative aging of the respiratory system

An absolute quantified normal rate of change and normal range of functions of the respiratory system applicable to all older adults as they age is elusive. Like life expectancy, which is dependent on a cohort effect, the norms of respiratory system function are related to the birth cohort to which a given individual belongs and the age at which the parameter is assessed. No single rate of change can express normal across all age ranges even for those individuals in apparently good health [29]. Analogous to defining risk factors for a disease, determining that a change in anatomy or physiology is not disease requires stringent prospective evaluation for the absence of occult disease and known risk factors for disease prior to concluding that the alteration is inevitable with the normal aging process [19,31]. Additional limitations in quantifying the norms of respiratory function with age are the lack of participation of the oldest adults in studies and the lack of precision and accuracy in these performance-based measurements. The data, although limited, do support a qualitative emphysematous change in lung histology and lung-thorax mechanics. This change plus altered lung volumes influence oxygenation and oxygen consumption. There is no evidence that the changes in the respiratory system with aging impact day-to-day function of older adults, but they may become evident under circumstances when physiologic demand reaches the limits of supply. Despite changes in cholinergic and adrenergic receptor functioning, there is no evidence to suggest altering prescribing these classes of medications for older people. Pioneer physiologists asked the original question "Is there a difference in this measurement for older people?" Researchers in pulmonary medicine, pathology, radiology, epidemiology, and public health have continued to revise the question toward the clinical implications while studying the aging process from their respective viewpoints. Clinicians who need to develop an integrated care plan should neither rely on formulas to "normalize" a measurement for age nor assume that a established predictive value of a diagnostic test done in young adults can be automatically applied to geriatric patients [4]. Rather, the clinical situation should consider that the variability in normal is greater with older age and that all diagnostic tests and care plans should be considered in the context of the patient's symptoms [5].     

Cognition enhancing or neuroprotective compounds for the treatment of cognitive disorders: why? when? which?

Neurodegenerative disorders such as Alzheimer's disease, Lewy-Body dementia, Parkinson's disease and cerebrovascular dementia result in an insidious cognitive and behavioural decline culminating in the development of severe dementia. Based on current population projections it has been estimated that by 2050 the number of individuals over 65 will increase to 1.1 billion worldwide and as a consequence, the number of cases of dementia to 37 million. Faced with such an enormous public health and socio-economic burden it is evident that the importance of therapeutic intervention aimed at either finding a cure or preventing disease progression cannot be overstated. The aim of the present paper is to present an overview, in the context of a brain aging continuum, at what stage cognition enhancing and/or neuroprotective intervention strategies aimed at stabilising and/or preventing neurodegenerative disease could demonstrate potential clinical benefit. In particular, the clinical identification of patients with mild cognitive impairment and age-associated memory impairment which may represent a 'transition' state between normal aging and dementia is discussed as a potential clinical population cohort targeted for early intervention in dementia. Considering the wide spectrum of cognitive and psychotic effects in dementia juxtaposed with the neuropathological evolution of the disease, it is clear that a variety of therapeutic intervention(s) will be required in order, to at the least, stabilise disease progression. Evidently, since Alzheimer's disease is by far the most prevalent form of dementia, and will undoubtedly serve as the benchmark for any future treatment of dementia, an update of current symptomatic and disease-modifying therapeutic approaches (cholinergic, glutamatergic, nootropics, beta-amyloid cascade inhibitors) will be reviewed.     

Sleep disordered breathing in the elderly

Sleep disordered breathing (SDB), i.e., obstructive, central or mixed sleep apneas, has been recognized as a common occurrence in the elderly. Aging is per se associated with a decrease in the quality of sleep; SDB may further disrupt the sleep architecture in older subjects. The prevalence of obstructive sleep apnea (OSA) increases with aging; available studies report prevalence rates of 11-62%. Furthermore, OSA has been associated with increased mortality in older adults. Central apneas and periodic breathing occur with increased frequency either in subjects with neurological disorders such as infarction, tumor, sequelae of infection, diffuse encephalopathies, or in chronic heart failure. Patients with cerebrovascular disease (stroke, or transient ischemic attacks) have a markedly high prevalence of SDB, mainly OSA. In these patients, SDB is associated with a poorer functional prognosis at 3 and 12 months after the acute event, and a higher mortality. The clinical impact of SDB on cognitive function appears to be modest in patients without dementia, although there is a moderate increase in daytime sleepiness. In Alzheimer's disease (AD) however, SDB occurs more frequently than in non-demented older subjects, and its severity is correlated with the degree of cognitive impairment. The hypothesis of a causal relationship between AD and SDB remains a subject of controversy. The possibility of SDB should be considered in the elderly in the differential diagnosis of "reversible dementias", increased daytime sleepiness, or unexplained right-sided heart failure.