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Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study.

ABSTRACT: Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status. Moreover, participants with severe(Braak stage V-VI) AD pathology who remained not demented represent only 12% (Nun Study) and 8% (ACT study) of nondemented subjects. Comparison of these subjects to those who were demented revealed that the former group was often significantly memory-impaired despite not being classified as demented. Most of these nondemented participants showed only stage V neurofibrillary pathology and frontal tangle counts that were slightly lower than a comparable (Braak stage V) dementia group. In summary, these data indicate that, in individuals with AD-type pathology who do not meet criteria for dementia, neocortical neurofibrillary tangles are somewhat reduced and incipient cognitive decline is present. Our data provide a foundation for helping to define additional factors that may impair, or be protective of, cognition in older adults.

SUBMITTER: SantaCruz KS

PROVIDER: S-EPMC3445265 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study.

SantaCruz Karen S KS Sonnen Joshua A JA Pezhouh Maryam Kherad MK Desrosiers Mark F MF Nelson Peter T PT Tyas Suzanne L SL

Journal of neuropathology and experimental neurology 20111001 10

Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status ...[more]

PMID: 21937909

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Project description:BackgroundAir pollution may be associated with elevated dementia risk. Prior research has limitations that may affect reliability, and no studies have evaluated this question in a population-based cohort of men and women in the United States.ObjectivesWe evaluated the association between time-varying, 10-y average fine particulate matter (PM2.5) exposure and hazard of all-cause dementia. An additional goal was to understand how to adequately control for age and calendar-time-related confounding through choice of the time axis and covariate adjustment.MethodsUsing the Adult Changes in Thought (ACT) population-based prospective cohort study in Seattle, we linked spatiotemporal model-based PM2.5 exposures to participant addresses from 1978 to 2018. Dementia diagnoses were made using high-quality, standardized, consensus-based protocols at biennial follow-ups. We conducted multivariable Cox proportional hazards regression to evaluate the association between time-varying, 10-y average PM2.5 exposure and time to event in a model with age as the time axis, stratified by apolipoprotein E (APOE) genotype, and adjusted for sex, education, race, neighborhood median household income, and calendar time. Alternative models used calendar time as the time axis.ResultsWe report 1,136 cases of incident dementia among 4,166 individuals with nonmissing APOE status. Mean [mean ± standard deviation (SD)] 10-y average PM2.5 was 10.1 (±2.9) μg/m3. Each 1-μg/m3 increase in the moving average of 10-y PM2.5 was associated with a 16% greater hazard of all-cause dementia [1.16 (95% confidence interval: 1.03, 1.31)]. Results using calendar time as the time axis were similar.DiscussionIn this prospective cohort study with extensive exposure data and consensus-based outcome ascertainment, elevated long-term exposure to PM2.5 was associated with increased hazard of all-cause dementia. We found that optimal control of age and time confounding could be achieved through use of either age or calendar time as the time axis in our study. Our results strengthen evidence on the neurodegenerative effects of PM2.5. https://doi.org/10.1289/EHP9018.

Project description:BackgroundDetecting patients with undiagnosed dementia is an important clinical challenge. Changes in medication adherence might represent an early sign of cognitive impairment. We sought to examine antihypertensive and statin adherence trajectories in community-dwelling older adults, comparing people who went on to develop dementia to those who did not.MethodsWe analyzed data from Adult Changes in Thought (ACT), a population-based cohort study embedded within an integrated healthcare delivery system. Analyses included 4368 participants aged ?65?years who had at least one follow-up visit. Research-quality dementia diagnoses were used to identify cases. We selected non-dementia control visits matched on age, sex, and study cohort that occurred at similar ACT follow-up time as the case's dementia onset; we treated this as the index date. Participants were included if they were prevalent users of either a statin or antihypertensive medication on the first day of follow up - 3?years prior to the index date. Using prescription fill dates and days supply, we calculated daily binary medication availability measures for each participant ('days covered') over 3?years leading up to the index date. We used group-based trajectory models to identify patterns of antihypertensive and statin adherence, and used conditional logistic regression to examine associations between adherence trajectories and dementia.ResultsFour trajectories were identified for antihypertensive users (292 cases, 3890 control visits), including near perfect (n =?1877, 36.6% cases, 45.5% controls), high (n =?1840, 43.2% cases, 44.1% controls), moderate (n =?365, 18.5% cases, 8.0% controls) and early poor adherence (n =?100, 1.7% cases, 2.4% controls). Odds of dementia was 3 times greater for those with moderate antihypertensive adherence compared to those with near perfect adherence (adjusted OR 3.0, 95% CI 2.0, 4.3). Four trajectories were identified for statin users (148 cases, 1131 control visits), including high (n =?1004, 75.0% cases, 79.0% controls), moderate (n =?192, 19.6% cases, 14.4% controls), early poor (n =?43, 2.0% cases, 3.5% controls), and delayed poor adherence (n =?40, 3.4% cases, 3.1% controls). No association was detected between statin adherence trajectories and dementia.ConclusionsPatterns of medication adherence may be useful to identify a subset of people at higher likelihood of developing dementia.

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Dataset Information

Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study.

Publications

Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study.

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