Abstract
Background
Current evidence on the association between Mediterranean diet (MeDi) intake and activities of daily living (ADL) is limited and inconsistent in older adults.
Methods
This study ...included 1 696 participants aged ≥65 years in the Washington Heights–Inwood Community Aging Project study. The MeDi score was calculated based on data collected from the Willett’s semiquantitative food frequency questionnaire. The multivariable-adjusted Cox regression model was applied to examine the association of MeDi score with risks of disability in basic (BADL) and instrumental ADL (IADL), as well as the overall ADL (B-IADL).
Results
Eight hundred and thirty-two participants with incident ADL disability were identified over a median follow-up of 5.39 years. The continuous MeDi score was significantly associated with decreased risk of disability in B-IADL (hazard ratio = 0.95, 95% confidence interval = 0.91–0.99, p = .018) in a model adjusted for age, sex, race/ethnicity, educational level, and dietary calories intake but was no longer significant after additionally adjusted for multiple comorbidities and physical activities (0.97 0.93, 1.01, p = .121). The continuous MeDi score was significantly associated with decreased risk of disability in B-IADL (0.92 0.85, 1.00, p = .043) and BADL (0.90 0.82, 0.99, p = .030) in non-Hispanic Whites, but not in non-Hispanic Blacks and Hispanics (p > .05 for all).
Conclusions
Higher MeDi score was associated with decreased risk of ADL disability, particularly in non-Hispanic Whites.
The entorhinal cortex has been implicated in the early stages of Alzheimer's disease, which is characterized by changes in the tau protein and in the cleaved fragments of the amyloid precursor ...protein (APP). We used a high-resolution functional magnetic resonance imaging (fMRI) variant that can map metabolic defects in patients and mouse models to address basic questions about entorhinal cortex pathophysiology. The entorhinal cortex is divided into functionally distinct regions, the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC), and we exploited the high-resolution capabilities of the fMRI variant to ask whether either of them was affected in patients with preclinical Alzheimer's disease. Next, we imaged three mouse models of disease to clarify how tau and APP relate to entorhinal cortex dysfunction and to determine whether the entorhinal cortex can act as a source of dysfunction observed in other cortical areas. We found that the LEC was affected in preclinical disease, that LEC dysfunction could spread to the parietal cortex during preclinical disease and that APP expression potentiated tau toxicity in driving LEC dysfunction, thereby helping to explain regional vulnerability in the disease.
To determine the predictive utility of baseline odor identification deficits for future cognitive decline and the diagnosis of Alzheimer disease (AD) dementia.
In a multiethnic community cohort in ...North Manhattan, NY, 1,037 participants without dementia were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). In 757 participants, follow-up occurred at 2 years and 4 years.
In logistic regression analyses, lower baseline UPSIT scores were associated with cognitive decline (relative risk 1.067 per point interval; 95% confidence interval CI 1.040, 1.095; p < 0.0001), and remained significant (relative risk 1.065 per point interval; 95% CI 1.034, 1.095; p < 0.0001) after including covariates. UPSIT, but not Selective Reminding Test-total immediate recall, predicted cognitive decline in participants without baseline cognitive impairment. During follow-up, 101 participants transitioned to AD dementia. In discrete time survival analyses, lower baseline UPSIT scores were associated with transition to AD dementia (hazard ratio 1.099 per point interval; 95% CI 1.067, 1.131; p < 0.0001), and remained highly significant (hazard ratio 1.072 per point interval; 95% CI 1.036, 1.109; p < 0.0001) after including demographic, cognitive, and functional covariates.
Impairment in odor identification was superior to deficits in verbal episodic memory in predicting cognitive decline in cognitively intact participants. The findings support the cross-cultural use of a relatively inexpensive odor identification test as an early biomarker of cognitive decline and AD dementia. Such testing may have the potential to select/stratify patients in treatment trials of cognitively impaired patients or prevention trials in cognitively intact individuals.
The global prevalence of dementia is as high as 24 million, and has been predicted to quadruple by the year 2050. In the US alone, Alzheimer disease (AD) – the most frequent cause of dementia ...characterized by a progressive decline in cognitive function in particular the memory domain – causes estimated health-care costs of $ 172 billion per year. Key neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques – often surrounded by dystrophic neurites – and intracellular neurofibrillary tangles. These pathological changes are frequently accompanied by reactive microgliosis and loss of neurons, white matter and synapses. The etiological mechanisms underlying these neuropathological changes remain unclear, but are probably caused by both environmental and genetic factors. In this review article, we provide an overview of the epidemiology of AD, review the biomarkers that may be used for risk assessment and in diagnosis, and give suggestions for future research.
•Ambient air pollution is associated with more rapid cognitive decline in older adults.•APOE-ε4 positive individuals had more rapid pollution-associated cognitive decline.•The association was also ...stronger among Non-Hispanic individuals.•No difference in strength of association between age groups, sex, or smoking status.
There is mounting evidence that long-term exposure to air pollution is related to accelerated cognitive decline in aging populations. Factors that influence individual susceptibility remain largely unknown, but may involve the apolipoprotein E genotype E4 (APOE-ε4) allele.
We assessed whether the association between long-term exposure to ambient air pollution and cognitive decline differed by APOE-ε4 status and cognitive risk factors.
The Washington Heights Inwood Community Aging Project (WHICAP) is a prospective study of aging and dementia. Neuropsychological testing and medical examinations occur every 18–24 months. We used mixed-effects models to evaluate whether the association between markers of ambient air pollution (nitrogen dioxide NO2), fine PM2.5, and coarse PM10 particulate matter) and the rate of decline in global and domain-specific cognition differed across strata defined by APOE-ε4 genotypes and cognitive risk factors, adjusting for sociodemographic factors and temporal trends.
Among 4821 participants with an average of 6 years follow-up, higher concentrations of ambient air pollution were associated with more rapid cognitive decline. This association was more pronounced among APOE-ε4 carriers (p < 0.001). A one interquartile range increase in NO2 was associated with an additional decline of 0.09 standard deviations (SD) (95%CI −0.1, −0.06) in global cognition across biennial visits among APOE-ε4 positive individuals and a 0.07 SD (95%CI −0.09, −0.05) decline among APOE-ε4 negative individuals. Results for PM2.5, PM10 and cognitive domains were similar. The association between air pollutants and rate of cognitive decline also varied across strata of race-ethnicity with the association strongest among White non-Hispanic participants.
These results add to the body of evidence on the adverse impact of ambient air pollution on cognitive aging and brain health and provide new insights into the genetic and behavioral factors that may impact individual susceptibility.
The associations between self-reported current and past leisure time physical activity (LTPA) and Alzheimer's disease (AD) incidence were determined using data from the multiethnic ...Washington/Hamilton Heights-Inwood Columbia Aging Project (WHICAP) study.
The metabolic equivalent of LTPA energy expenditure was calculated for self-reported current and past LTPA for 1345 older adults. A Cox proportional hazard model was conducted to estimate the association between LTPA (low, middle, and high) and incident AD risk.
Comparing high to low level, current and past LTPA were both associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.39 (0.20–0.75) and 0.37 (0.18–0.75), respectively. Compared with “always low,” “increased” and “always high” LTPA throughout life were associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.60 (0.36–0.99) and 0.28 (0.08–0.94), respectively. Light- and moderate-intensity LTPA were associated with lower AD risk.
LTPA both throughout life and later in life are associated with lower risk of AD.
•More current and earlier-life LTPA were associated with reduced risk of Alzheimer's disease (AD).•Increasing or maintaining high LTPA throughout life was protective against AD.•Avoiding being physically inactive throughout life was beneficial for prevention of AD.•There was a health benefit in AD prevention by performing light and moderate LTPAs.
To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD.
We ...have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study.
We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p < 10(-16), r2 > 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex.
Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.
Our group has previously studied the brains of some unique individuals who are able to tolerate robust amounts of Alzheimer's pathological lesions (amyloid plaques and neurofibrillary tangles) ...without experiencing dementia while alive. These rare resilient cases do not demonstrate the patterns of neuronal/synaptic loss that are normally found in the brains of typical demented Alzheimer's patients. Moreover, they exhibit decreased astrocyte and microglial activation markers GFAP and CD68, suggesting that a suppressed neuroinflammatory response may be implicated in human brain resilience to Alzheimer's pathology. In the present work, we used a multiplexed immunoassay to profile a panel of 27 cytokines in the brains of controls, typical demented Alzheimer's cases, and two groups of resilient cases, which possessed pathology consistent with either high probability (HP, Braak stage V-VI and CERAD 2–3) or intermediate probability (IP, Braak state III-IV and CERAD 1–3) of Alzheimer's disease in the absence of dementia. We used a multivariate partial least squares regression approach to study differences in cytokine expression between resilient cases and both Alzheimer's and control cases. Our analysis identified distinct profiles of cytokines in the entorhinal cortex (one of the earliest and most severely affected brain regions in Alzheimer's disease) that are up-regulated in both HP and IP resilient cases relative to Alzheimer's and control cases. These cytokines, including IL-1β, IL-6, IL-13, and IL-4 in HP resilient cases and IL-6, IL-10, and IP-10 in IP resilient cases, delineate differential inflammatory activity in brains resilient to Alzheimer's pathology compared to Alzheimer's cases. Of note, these cytokines all have been associated with pathogen clearance and/or the resolution of inflammation. Moreover, our analysis in the superior temporal sulcus (a multimodal association cortex that consistently accumulates Alzheimer's pathology at later stages of the disease along with overt symptoms of dementia) revealed increased expression of neurotrophic factors, such as PDGF-bb and basic FGF in resilient compared to AD cases. The same region also had reduced expression of chemokines associated with microglial recruitment, including MCP-1 in HP resilient cases and MIP-1α in IP resilient cases compared to AD. Altogether, our data suggest that different patterns of cytokine expression exist in the brains of resilient and Alzheimer's cases, link these differences to reduced glial activation, increased neuronal survival and preserved cognition in resilient cases, and reveal specific cytokine targets that may prove relevant to the identification of novel mechanisms of brain resiliency to Alzheimer's pathology.
•Certain individuals resist neurodegeneration despite robust Alzheimer's pathology.•Resilient cases are distinguished by unique cytokine expression profiles.•Cytokines associated with resiliency are neuroprotective and chemotactic.•Cytokine profiles may inform new strategies to combat Alzheimer's neurodegeneration.
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