The Rush Alzheimer's Disease Center (RADC) is a research center located in Rush University Medical Center. The Rush Alzheimer's Disease Center is one of 29 Alzheimer's centers in the U.S. designated and funded by the National Institute on Aging.The RADC is a leader in research into the causes and treatment of Alzheimer's disease.One of its earliest research projects was the Religious Orders Study. An important influence on the development of the Religious Orders Study was the Nun Study founded by Dr. David Snowdon. The Religious Orders Study was initially funded by the National Institute on Aging in 1993. It is a study utilizing volunteers in the religious community, including priests, nuns, and brothers, who agree to donate their brains to the RADC after they die, providing doctors with an opportunity to look for postmortem correlations between lifestyle and Alzheimer’s disease. Scientists at the RADC use the brains to study a broad range of factors relating to Alzheimer's disease and other common diseases of age, and share tissue samples from those brains, as well as data, with other medical institutions around the country.The RADC's Memory and Aging Project (MAP) followed in 1997 and uses volunteers from the community. The study design is similar to the Religious Orders Study and enrolls volunteers without dementia who agree to annual clinical evaluation and organ donation.Both studies are ongoing, and have created research opportunities at Rush University, including the Mediterranean-DASH Intervention for Neurodegenerative Delay MIND diet research, Minority Aging Research Study (MARS), which is a study of decline in cognitive function and risk of Alzheimer's disease in older African Americans, with brain donation after death added as an optional component, the Latino CORE study, relating to older Latino adults, and a study newly-funded by NIA to study Alzheimer's disease in Brazil.The RADC also sponsors an array of community outreach and education programs..
The existence of human hippocampal neurogenesis has long been disputed1-12 and its relevance in cognition remains unknown. Recent studies have established the presence of proliferating progenitors and immature neurons and a reduction in the latter in Alzheimer's disease (AD)11,13. However, their origin and the molecular networks that regulate neurogenesis and function are poorly understood. Here we studied human post-mortem hippocampi obtained from different cohorts: young adults with intact memory, aged adults with no cognitive impairments, aged adults with extraordinary memory capacity (SuperAgers)14,15, adults with preclinical intermediate pathology or adults with AD. Using multiomic single-cell sequencing (single-nucleus RNA sequencing and single-nuclei assay for transposase-accessible chromatin with sequencing), we analysed the profiles of 355,997 nuclei isolated from the hippocampus samples and identified neural stem cells, neuroblasts and immature granule neurons. Dysregulated neurogenesis was largely associated with changes in chromatin accessibility. Analyses of transcription factors and target gene signatures that distinguished each of the groups revealed early alterations in chromatin accessibility of neurogenic cells from individuals with preclinical AD, and such changes were even more evident in samples from individuals with AD. We identified a distinct profile of neurogenesis in SuperAgers that may reflect a 'resilience signature'. Finally, alterations in the profile of astrocytes and CA1 neurons govern cognitive function in the ageing hippocampus. Together, our study points to a multiomic molecular signature of the hippocampus that distinguishes cognitive resilience and deterioration with ageing.
Background Cognitive decline has been reported after coronary artery revascularization, but whether it reflects procedure-specific effects or the burden of underlying vascular disease remains uncertain. Objectives To determine whether incident dementia risk differs according to coronary revascularization strategy among older adults with acute coronary syndrome (ACS). Methods We conducted a longitudinal cohort study among adults aged ≥65 years hospitalized for ACS between 2010 and 2020 (n = 25,176). Patients underwent percutaneous coronary intervention (n = 8,043), coronary artery bypass grafting (n = 797), or received no revascularization (n = 16,336). A second comparator cohort included patients with stable coronary artery disease (CAD) without revascularization (n = 154,299). The primary outcome was incident dementia identified using validated International Classification of Diseases codes after a 1-year washout. Propensity-matched analyses used Cox models accounting for the competing risk of death. Results Revascularized patients were younger (74.8 ± 6.9 vs 77.1 ± 8.2 years), more often male (66.2% vs 54.0%), and had lower Elixhauser multimorbidity scores (4.6 ± 2.8 vs 5.4 ± 3.0, all P < 0.001). Over a median 4.8 years of follow-up, 9.0% of ACS patients developed dementia. Revascularization was not associated with increased dementia risk compared with ACS without revascularization (sub-hazard ratio: 1.05; 95% CI: 0.95-1.17) or stable CAD. Dementia risk was also similar between percutaneous coronary intervention and coronary artery bypass grafting. Conclusions We found that among older adults with ACS, coronary revascularization was not statistically significantly associated with increased dementia risk compared with no revascularization or stable CAD. These findings reflect the hypothesis that the majority of dementia risk is potentially driven more by cumulative vascular and systemic factors than by procedure-specific neurotoxicity.
INTRODUCTION:We investigated the association between retirement, age at retirement, and domain-specific cognitive decline. METHODS:Three hundred twenty-one participants aged 65+ from the Study of Healthy Aging in African Americans completed verbal episodic memory (VEM) and executive function (EF) assessments across three waves (every 16 months). Linear mixed-effects models with random intercepts and slopes examined associations of retirement status (retired, not retired) and timing (retired before age 65, retired at 65+, and not retired) with cognitive decline adjusting for demographics and parental education. RESULTS:Participants' mean age was 74.6 ± 6.9, 65% were women, and 87% were retired (33% at age 65+). Retirement status and timing were not associated with baseline cognition. Over 2.11 ± 0.66 years, non-retirees had slower EF decline than retirees (b = 0.11 [0.03, 0.19]). Participants who retired at 65+ had slower VEM decline than those who retired before 65 (b = 0.11 [0.02, 0.21]). DISCUSSION:Retirement and early retirement were associated with faster cognitive decline among Black/African American adults.
Background: Others have examined heterogeneity in Alzheimer's disease (AD); however, few have used longitudinal data while accounting for variation in disease stage. We used latent classes to model heterogeneity in the trajectories of three cognitive domains (memory, language, and executive functioning) starting at AD dementia diagnosis. Objective: Our aim was to describe the patterns of heterogeneity in cognitive decline across cognitive domains during the course of AD and to contextualize our findings by assessing associations with demographic factors and neuropathological measures. Methods: We used cognitive data from the Religious Orders Study, the Rush Memory and Aging Project, and the Minority Aging Research Study in a multi-dimensional joint latent class mixed model, which allowed us to estimate cognitive trajectories that varied across cognitive domains and latent classes. We accounted for the uncertainty in latent class assignment and corrected for multiple hypotheses when assessing the association of the latent classes with demographic and neuropathological variables. Results: We identified five latent classes differentiated by level of impairment (high to low) and rate of decline (slow to fast). Within each latent class, the pattern of decline did not differ substantially across cognitive domains. Classes were associated with APOE genotype, sex, race, education, and neuritic plaque and neurofibrillary tangle burden. Conclusions: Our results highlight global differences in the level of cognitive impairment at diagnosis and the rate of decline rather than differences between domains of cognition. Examination of patterns in the global rate of cognitive decline may improve understanding of heterogeneity in AD.
