Postmortem Brain Imaging in Alzheimer\u27s Disease and Related Dementias: The South Texas Alzheimer\u27s Disease Research Center Repository

Background: Neuroimaging bears the promise of providing new biomarkers that could refine the diagnosis of dementia. Still, obtaining the pathology data required to validate the relationship between neuroimaging markers and neurological changes is challenging. Existing data repositories are focused on a single pathology, are too small, or do not precisely match neuroimaging and pathology findings. Objective: The new data repository introduced in this work, the South Texas Alzheimer’s Disease research center repository, was designed to address these limitations. Our repository covers a broad diversity of dementias, spans a wide age range, and was specifically designed to draw exact correspondences between neuroimaging and pathology data. Methods: Using four different MRI sequences, we are reaching a sample size that allows for validating multimodal neuroimaging biomarkers and studying comorbid conditions. Our imaging protocol was designed to capture markers of cerebrovascular disease and related lesions. Quantification of these lesions is currently underway with MRI-guided histopathological examination. Results: A total of 139 postmortem brains (70 females) with mean age of 77.9 years were collected, with 71 brains fully analyzed. Of these, only 3% showed evidence of AD-only pathology and 76% had high prevalence of multiple pathologies contributing to clinical diagnosis. Conclusion: This repository has a significant (and increasing) sample size consisting of a wide range of neurodegenerative disorders and employs advanced imaging protocols and MRI-guided histopathological analysis to help disentangle the effects of comorbid disorders to refine diagnosis, prognosis and better understand neurodegenerative disorders

Daily Energy Intake Distribution and Cognitive Performance in Non-Demented Individuals

Cognitive disorders have become important public health issues around the world. Studies evaluating the association between cognitive decline and food timing are lacking. The objective of this study was to examine the potential association between energy intake distribution during the day and cognitive performance in cognitively healthy and mildly cognitive impaired individuals. Data were derived from the ongoing Albion study which includes people aged 40 years or older who have a positive family history of cognitive disorder or concern about their cognitive status. A thorough dietary and cognitive assessment was performed. Participants consuming low energy intake at the beginning of the day or high energy at the end of the day had higher cognitive function compared to participants characterized by the opposite pattern. This trend remained statistically significant even after adjustment for potential confounders (p = 0.043). This study suggests that individuals with worse cognitive function may choose to eat earlier during the day, when cognitive performance is better, and it might be hypothesized that a meal pattern characterized by high energy consumption at the beginning of the day or low energy at the end of the day could be a marker of cognitive impairment

Sleep Polygenic Risk Score Is Associated with Cognitive Changes over Time

Sleep problems have been associated with cognition, both cross-sectionally and longitudinally. Specific genes have been also associated with both sleep regulation and cognition. In a large group of older non-demented adults, we aimed to (a) validate the association between Sleep Polygenic Risk Score (Sleep PRS) and self-reported sleep duration, and (b) examine the association between Sleep PRS and cognitive changes in a three-year follow-up. Participants were drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A structured, in-person interview, consisting of a medical history report and physical examination, was conducted for each participant during each of the visits (baseline and first follow-up). In total, 1376 participants were included, having all demographic, genetic, and cognitive data, out of which, 688 had at least one follow-up visit. In addition, an extensive neuropsychological assessment examining five cognitive domains (memory, visuo-spatial ability, attention/speed of processing, executive function, and language) was administered. A PRS for sleep duration was created based on previously published, genome-wide association study meta-analysis results. In order to assess the relationship between the Sleep PRS and the rate of cognitive change, we used generalized estimating equations analyses. Age, sex, education, ApolipoproteinE-ε4 genotype status, and specific principal components were used as covariates. On a further analysis, sleep medication was used as a further covariate. Results validated the association between Sleep PRS and self-reported sleep duration (B = 1.173, E-6, p = 0.001). Further, in the longitudinal analyses, significant associations were indicated between increased Sleep PRS and decreased visuo-spatial ability trajectories, in both the unadjusted (B = −1305.220, p = 0.018) and the adjusted for the covariates model (B = −1273.59, p = 0.031). Similarly, after adding sleep medication as a covariate (B = −1372.46, p = 0.019), none of the associations between Sleep PRS and the remaining cognitive domains were significant. PRS indicating longer sleep duration was associated with differential rates of cognitive decline over time in a group of non-demented older adults. Common genetic variants may influence the association between sleep duration and healthy aging/cognitive health

The Longitudinal Association of Lifestyle with Cognitive Health and Dementia Risk: Findings from the HELIAD Study

The aim of the current study was to investigate whether a Total Lifestyle Index (TLI), including adherence to the Mediterranean diet, sleep duration, physical activity and engagement in activities of daily living, is associated with cognitive health over time and dementia risk, in a representative cohort of older people. A total of 1018 non-demented community-dwelling older adults ≥65 years old (60% women) from the HELIAD study were included. A comprehensive neurological and neuropsychological assessment was conducted at baseline and at the 3-year follow-up evaluating cognitive functioning, and a dementia diagnosis was set. Diet, physical activity, sleep duration and engagement in activities of daily living were assessed using standard, validated questionnaires at baseline. Sixty-one participants developed dementia at follow-up; participants who developed dementia were older and had fewer years of education compared with participants with normal cognition. With the exception of sleep duration, participants with normal cognition at follow-up scored higher in the individual lifestyle factors compared to those who developed dementia. Regarding TLI, values were lower for participants with dementia compared with those with normal cognition. Each additional unit of the TLI was associated with 0.5% of a standard deviation less decline per year of the Global Cognition score, whereas for each additional unit of the TLI, the risk for dementia was reduced by 0.2% per year (p < 0.05). Our results suggest that greater adherence to a healthy lifestyle pattern is associated with a slower decline of cognitive function and reduced dementia risk

Sleep Polygenic Risk Score Is Associated with Cognitive Changes over Time

Sleep problems have been associated with cognition, both cross-sectionally and longitudinally. Specific genes have been also associated with both sleep regulation and cognition. In a large group of older non-demented adults, we aimed to (a) validate the association between Sleep Polygenic Risk Score (Sleep PRS) and self-reported sleep duration, and (b) examine the association between Sleep PRS and cognitive changes in a three-year follow-up. Participants were drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A structured, in-person interview, consisting of a medical history report and physical examination, was conducted for each participant during each of the visits (baseline and first follow-up). In total, 1376 participants were included, having all demographic, genetic, and cognitive data, out of which, 688 had at least one follow-up visit. In addition, an extensive neuropsychological assessment examining five cognitive domains (memory, visuo-spatial ability, attention/speed of processing, executive function, and language) was administered. A PRS for sleep duration was created based on previously published, genome-wide association study meta-analysis results. In order to assess the relationship between the Sleep PRS and the rate of cognitive change, we used generalized estimating equations analyses. Age, sex, education, ApolipoproteinE-epsilon 4 genotype status, and specific principal components were used as covariates. On a further analysis, sleep medication was used as a further covariate. Results validated the association between Sleep PRS and self-reported sleep duration (B = 1.173, E-6, p = 0.001). Further, in the longitudinal analyses, significant associations were indicated between increased Sleep PRS and decreased visuo-spatial ability trajectories, in both the unadjusted (B = -1305.220, p = 0.018) and the adjusted for the covariates model (B = -1273.59, p = 0.031). Similarly, after adding sleep medication as a covariate (B = -1372.46, p = 0.019), none of the associations between Sleep PRS and the remaining cognitive domains were significant. PRS indicating longer sleep duration was associated with differential rates of cognitive decline over time in a group of non-demented older adults. Common genetic variants may influence the association between sleep duration and healthy aging/cognitive health