Dementia in the oldest old (original) (raw)

… England Journal of …, 2009

Research in Alzheimer's disease is focused mainly on younger old persons, whereas studies involving very old persons report attenuated relationships between the pathological features of Alzheimer's disease and dementia.

Neuropathology of Cognitively Normal Elderly

Journal of Neuropathology and Experimental Neurology, 2003

Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed, cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage ϽIV; 32 subjects (82%) with less than moderate numbers of cored plaques and 37 subjects (95%) with less than moderate numbers of tau-positive neuritic plaques. Many subjects had moderate or frequent diffuse plaques (n ϭ 19, 49%). By the National Institute on Aging-Reagan Institute (NIA-RI) criteria, none of our cases met criteria for high ''likelihood'' of AD. Four met NIA-RI criteria for intermediate ''likelihood.'' Seven cases met CERAD criteria for possible AD. Nineteen met Khachaturian criteria for AD. Only 1 subject had neocortical Lewy bodies. Small, old infarcts were common, but no subjects had more than 2 of these and none had a single large infarction. Thus, the majority of individuals who are cognitively normal near the time of their death have minimal amounts of tau-positive neuritic pathology (Braak stage ϽIV and neuritic plaques Ͻ6 per ϫ100 field in the most affected neocortical region). The few subjects with more severe AD pathology can be expected based on incidence rates of AD in the very elderly.

The neuropathology of older persons with and without dementia from community versus clinic cohorts

Journal of Alzheimer's disease : JAD, 2009

Community-based cohorts of older persons may differ neuropathologically from clinic-based cohorts. This study investigated age-related pathologies in persons with and without dementia and included autopsied participants from two community-based cohorts, the Rush Religious Orders Study (n=386) and the Memory and Aging Project (n=195), and one clinic-based cohort, the Clinical Core of the Rush Alzheimer's Disease Center (n=392). Final clinical diagnoses included no cognitive impairment (n=202), mild cognitive impairment (MCI) (n=150), probable Alzheimer's disease (AD) (n=474), possible AD (n=88), and other dementias (n=59). Postmortem diagnoses included pathologic AD, cerebral infarcts, and Lewy body disease. Community-based persons with clinical AD had less severe AD pathology (p<0.001) and had more cerebral infarcts (p<0.001) compared to clinic-based persons. Additionally, community-based persons with MCI had more infarcts compared to clinic-based persons. Overall, the...

Population-based analysis of pathological correlates of dementia in the oldest old

Annals of Clinical and Translational Neurology, 2017

Objective: The aim of this study was to analyze brain pathologies which cause dementia in the oldest old population. Methods: All 601 persons aged ≥85 years living in the city of Vantaa (Finland), on April 1st, 1991 formed the study population of the Vantaa85 + study, 300 of whom were autopsied during follow-up (79.5% females, mean age-at-death 92 AE 3.7 years). Alzheimer's disease (AD) pathology (tau and beta-amyloid [Ab]), cerebral amyloid angiopathy (CAA) and Lewy-related pathologies were analyzed. Brain infarcts were categorized by size (<2 mm, 2-15 mm, >15 mm) and by location. Brain hemorrhages were classified as microscopic (<2 mm) and macroscopic. Results: 195/300 (65%) were demented. 194/195 (99%) of the demented had at least one neuropathology. Three independent contributors to dementia were identified: AD-type tau-pathology (Braak stage V-VI), neocortical Lewy-related pathology, and cortical anterior 2-15 mm infarcts. These were found in 34%, 21%, and 21% of the demented, respectively, with the multivariate odds ratios (OR) for dementia 5.5, 4.5, and 3.4. Factor analysis investigating the relationships between different pathologies identified three separate factors: (1) AD-spectrum, which included neurofibrillary tau, Ab plaque, and neocortical Lewy-related pathologies and CAA (2) >2 mm cortical and subcortical infarcts, and (3) <2 mm cortical microinfarcts and microhemorrhages. Multipathology was common and increased the risk of dementia significantly. Interpretation: These results indicate that AD-type neurodegenerative processes play the most prominent role in twilight cognitive decline. The high prevalence of both neurodegenerative and vascular pathologies indicates that multiple preventive and therapeutic approaches are needed to protect the brains of the oldest old.

Neuropathology of older persons without cognitive impairment from two community-based studies

Neurology, 2006

To examine the relation of National Institute on Aging-Reagan (NIA-Reagan) neuropathologic criteria of Alzheimer disease (AD) to level of cognitive function in persons without dementia or mild cognitive impairment (MCI). Methods: More than 2,000 persons without dementia participating in the Religious Orders Study or the Memory and Aging Project agreed to annual detailed clinical evaluation and brain donation. The studies had 19 neuropsychological performance tests in common that assessed five cognitive domains, including episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. A total of 134 persons without cognitive impairment died and underwent brain autopsy and postmortem assessment for AD pathology using NIA-Reagan neuropathologic criteria for AD, cerebral infarctions, and Lewy bodies. Linear regression was used to examine the relation of AD pathology to level of cognitive function proximate to death. Results: Two (1.5%) persons met NIA-Reagan criteria for high likelihood AD, and 48 (35.8%) met criteria for intermediate likelihood; 29 (21.6%) had cerebral infarctions, and 18 (13.4%) had Lewy bodies. The mean Mini-Mental State Examination score proximate to death was 28.2 for those meeting high or intermediate likelihood AD by NIA-Reagan criteria and 28.4 for those not meeting criteria. In linear regression models adjusted for age, sex, and education, persons meeting criteria for intermediate or high likelihood AD scored about a quarter standard unit lower on tests of episodic memory (p ϭ 0.01). There were no significant differences in any other cognitive domain. Conclusions: Alzheimer disease pathology can be found in the brains of older persons without dementia or mild cognitive impairment and is related to subtle changes in episodic memory.

Challenges of diagnosing dementia in the oldest old population

People aged 90 and older are the fastest growing age group in most parts of the world. Since the prevalence of dementia has been shown to increase exponentially after the age of 65, there is an acceptance that the oldest old population has a high burden of dementia; however, there is a lack of consensus on how best to diagnose dementia in this population. This review summarizes the various approaches to diagnosing dementia and the prevalence and incidence rates of dementia that have been reported. We also summarize the literature on cognitive and functional performance and biomarkers for dementia and discuss the limitations to interpretation of these data. Finally, we make recommendations for both researchers and clinicians who intend to diagnose dementia in the oldest old population.

Prevalence of Alzheimer's disease in very elderly people: A prospective neuropathological study

Neurology, 2001

Article abstract-Background: No previous autopsy-controlled, prospective, and population-based studies are available on the prevalence of AD in very elderly people. Objective: To study the point prevalence of neuropathologically defined AD in a population of people at least 85 years of age, stratified according to their APOE genotype. Methods: A populationbased sample of 532 (of a total population of 601) elderly Finnish individuals, aged 85 years or more, were clinically tested for dementia in 1991 (with follow-up studies of the survivors in 1994, 1996, and 1999) and genotyped for APOE. An autopsy involving neuropathologic diagnosis of AD according to modified consensus criteria was performed in 118 of 198 deceased subjects who had been demented on April 1, 1991, and in 62 of 201 nondemented individuals. Results: The prevalence of neuropathologically defined AD was 33%, whereas the prevalence of clinically diagnosed AD was 16%. There was a highly significant (p Ͻ 0.001) association between the APOE ⑀4 allele and AD: Sixty-three percent of APOE ⑀4 carriers and 20% of noncarriers had neuropathologic AD. The respective figures in subjects aged 90 years or more were 71 and 22%. Conclusions: The prevalence of neuropathologically defined AD is higher than that reported in most previous studies based on clinical diagnosis. The discrepancy between the neuropathologic and clinical diagnoses of AD in very elderly subjects may affect the results of population-based studies. The APOE genotype has a strong effect on the prevalence of neuropathologically defined AD, even after 90 years of age.

Neuropathology and cognitive performance in self-reported cognitively healthy centenarians

Acta neuropathologica communications, 2018

With aging, the incidence of neuropathological hallmarks of neurodegenerative diseases increases in the brains of cognitively healthy individuals. It is currently unclear to what extent these hallmarks associate with symptoms of disease at extreme ages. Forty centenarians from the 100-plus Study cohort donated their brain. Centenarians self-reported to be cognitively healthy at baseline, which was confirmed by a proxy. Objective ante-mortem measurements of cognitive performance were associated with the prevalence, distribution and quantity of age- and AD-related neuropathological hallmarks. Despite self-reported cognitive health, objective neuropsychological testing suggested varying levels of ante-mortem cognitive functioning. Post-mortem, we found that neuropathological hallmarks related to age and neurodegenerative diseases, such as Aβ and Tau pathology, as well as atherosclerosis, were abundantly present in most or all centenarians, whereas Lewy body and pTDP-43 pathology were s...

Role of the Neuropathology of Alzheimer Disease in Dementia in the Oldest-Old

Archives of Neurology, 2008

Background-Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in the brain, especially in the hippocampus, entorhinal cortex, and isocortex, are hallmark lesions of Alzheimer disease and dementia in the elderly. However, this association has not been extensively studied in the rapidly growing population of the very old.

Risk factors for cognitive decline in healthy older adults

Neurobiology of Aging, 2000

Epidemiology (n=120) were demented at the time of their final examination. Of these 92 met neuropathological criteria for AD. Forty-six sisters met neuropathological criteria for AD, but were not demented at their last assessment. The 2X sisters who were demented, but did not fulfill AD neuropathologlc criteria, had a variety of pathologies, including cerebral infarcts, dementia with Lewy bodies, hydrocephalus and hippocampal sclerosis. APOE-•4,when adjurted for age, education and other variables, was associated with an elevated risk for meeting neuropathologic criteria for AD(OR=S.R. 95% CI: 2.7-12. I). Individuals with one or more ~4 alleles who fulfilled AD neuropathological criteria had a significant increase in dementia risk (OR=6.1,95% Cl: 2.7-13.6) compared to those who neither fulfilled AD neuropathologic criteria nor had t4 alleles. By contrast, in a similar comparison, individuals with ~4 alleles who did not meet AD neuropathologlc criteria were not at increased risk for dementia (OR=O.6, 95% Cl: 0.1-3.2). A series of analyses demonstrated strong associations between the presence of ~4 alleles and the severity of neurofibrillay tangles and senile plaques in the hippocampus and neocmtex. The findmgs indicate a strong association between APOE-~4 genotypea and an increased severity of Alrheimer neuropathol?gy regardless of clinical outcome, but do not provide support for an a?socntion between APOE-~4 and dementia resulting from other pathologler.

Dementia in the oldest old (original) (raw)

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