Sex differences in the association between age-related decline in blood pressure and decline in cognition: A prospective cohort study.

Background: Both high and declining blood pressure (BP) are associated with cognitive decline risk in older adults. In late-life, women have higher rates of hypertension, experience faster cognitive decline, and represent two-thirds of individuals with Alzheimer's disease dementia. However, sex differences in the association between BP decline and cognitive decline are unknown.

Brain phosphoproteomic analysis identifies diabetes-related substrates in Alzheimer's disease pathology in older adults.

Introduction: Type 2 diabetes increases the risk of Alzheimer's disease (AD) dementia. Insulin signaling dysfunction exacerbates tau protein phosphorylation, a hallmark of AD pathology. However, the comprehensive impact of diabetes on patterns of AD-related phosphoprotein in the human brain remains underexplored.

Late-life social activity and subsequent risk of dementia and mild cognitive impairment.

Introduction: Social activity is associated with better cognitive health in old age. To better translate epidemiological research for public health communication, we estimated relations of levels of social activity to average age at dementia onset.

Methods: In the Rush Memory and Aging Project (MAP), we followed 1923 dementia-free older adults and conducted annual clinical evaluations of dementia/mild cognitive impairment (MCI).

The MIND diet, brain transcriptomic alterations, and dementia.

Introduction: Dietary patterns are associated with dementia risk, but the underlying molecular mechanisms are largely unknown.

Methods: We used RNA sequencing data from post mortem prefrontal cortex tissue and annual cognitive evaluations from 1204 participants in the Religious Orders Study and Memory and Aging Project. We identified a transcriptomic profile correlated with the MIND diet (Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay) among 482 individuals who completed ante mortem food frequency questionnaires; and examined its associations with cognitive health in the remaining 722 participants.

Associations of renin-angiotensin system inhibitor use with brain insulin signaling and neuropathology.

Objective: To examine the associations of renin-angiotensin system (RAS) inhibitor use with postmortem brain insulin signaling and neuropathology.

Methods: Among Religious Orders Study participants, 150 deceased and autopsied older individuals (75 with diabetes matched to 75 without by age at death, sex, and education) had measurements of insulin receptor substrate-1 (IRS-1) and RAC-alpha serine/threonine protein kinase (AKT1) collected in the prefrontal cortex using ELISA and immunohistochemistry. Alzheimer's disease (AD), brain infarcts, and cerebral vessel pathology data were assessed by systematic neuropathologic evaluations.

Correlates of missed or late versus timely diagnosis of dementia in healthcare settings.

Introduction: There is limited evidence about factors related to the timeliness of dementia diagnosis in healthcare settings.

Methods: In five prospective cohorts at Rush Alzheimer's Disease Center, we identified participants with incident dementia based on annual assessments and examined the timing of healthcare diagnoses in Medicare claims. We assessed sociodemographic, health, and psychosocial correlates of timely diagnosis.

Association of Alzheimer's Disease and Other Neuropathologies With Functional Disability in Persons With and Without Dementia.

Background: Dementia results from multiple neuropathologies causing cognitive impairment sufficiently severe to affect functional status. However, these pathologies and functional impairment are common in persons without dementia. We examined the association of Alzheimer's disease (AD) and multiple other neuropathologies with instrumental and basic activities of daily living in persons with and without dementia.

Everyday Discrimination Is Associated With Higher Odds of Hospitalizations Among Older African Americans.

Background: Everyday discrimination-experiences of being treated unfairly based on background characteristics like race-is linked to poor physical and mental health throughout the lifespan. Whether more experiences of discrimination are associated with higher odds of being hospitalized in older African Americans has not been explored.

Methods: Community-dwelling participants from 3 longitudinal cohort studies (N = 446, age 65+ years) with discrimination scores and ≥12 months of linked Medicare claims were included.

Association of Age-Related Neuropathologic Findings at Autopsy With a Claims-Based Epilepsy Diagnosis in Older Adults.

Background And Objectives: Epilepsy is 1 of the 3 most common neurologic diseases of older adults, but few studies have examined its underlying pathologies in older age. We examined the associations of age-related brain pathologies with epilepsy in older persons.

Methods: Clinical and pathologic data came from 2 ongoing clinical pathologic cohort studies of community-dwelling older adults.

Associations of Serum Insulin and Related Measures With Neuropathology and Cognition in Older Persons With and Without Diabetes.

Objective: To examine associations of serum insulin and related measures with neuropathology and cognition in older persons.

Methods: We studied 192 older persons (96 with diabetes and 96 without, matched by sex and balanced by age-at-death, education, and postmortem interval) from a community-based, clinical-pathologic study of aging, with annual evaluations including neuropsychological testing (summarized into global cognition and 5 cognitive domains) and postmortem autopsy. We assessed serum insulin, glucose, leptin, adiponectin, hemoglobin A1C, advanced glycation-end products (AGEs), and receptors for advanced glycation-end products, and calculated the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and adiponectin-to-leptin ratio.

Atherosclerosis and Hippocampal Volumes in Older Adults: The Role of Age and Blood Pressure.

Background: Lower hippocampal volume is associated with late-life cognitive decline and is an important, but nonspecific marker for clinical Alzheimer's dementia. Cerebrovascular disease may also be associated with hippocampal volume. Here we study the role of intracranial large vessel disease (atherosclerosis) in association with hippocampal volume and the potential role of age, average late-life blood pressure across all visits, and other factors (sex, apolipoprotein ε4 [ ε4], and diabetes).

Brain Insulin Signaling is Associated with Late-Life Cognitive Decline.

Type-2 diabetes is associated with an increased risk of dementia, and the underlying mechanism might involve abnormal insulin signaling in the brain. The objective of this study was to examine the association of postmortem brain insulin signaling with late-life cognitive decline. Among participants of Religious Orders Study, a community-based clinical-pathological cohort, 150 deceased and autopsied older individuals (75 with diabetes matched to 75 without by age at death, sex, and education) had postmortem brain insulin signaling measurements collected in the prefrontal cortex using ELISA and immunohistochemistry.

Changes in an in-vivo classifier of ARTerioloSclerosis (ARTS) with simultaneous change in cognition for older African Americans.

At autopsy, African American decedents often have mixed Alzheimer's and cerebrovascular brain pathologies including arteriolosclerosis. We applied a novel in-vivo classifier of ARTerioloSclerosis (ARTS) in 167 older African Americans (∼75y of age) with > 2 biennial 3 T MRI scans and > 3 years of associated cognitive follow-up to determine if ARTS scores (higher score=higher likelihood of arteriolosclerosis) changed over time and if this change associated with changes in cognition in the same individuals. Mixed effects regression models tested whether ARTS scores increased over time, while simultaneous mixed effects regression models estimated the simultaneous rates of change in both ARTS and cognition and the correlation of these changes.

Changes in Body Mass Index and Incident Mild Cognitive Impairment Among African American Older Adults.

Background: Previous research suggests a decline in body mass index (BMI) among older adults is associated with negative health outcomes, including mild cognitive impairment (MCI) and incident dementia. However, no studies have examined the effects of education or developing MCI on BMI trajectories over time. The purpose of this investigation was to characterize trajectories of change in BMI among older adults who develop MCI.

Metformin, age-related cognitive decline, and brain pathology.

The objective of this study was to evaluate the relation of metformin with change in cognition and brain pathology. During a mean of 8 years (SD = 5.5) of annual follow-up visits, 262/3029 participants were using metformin at any time during the study.

nlive: an R package to facilitate the application of the sigmoidal and random changepoint mixed models.

Background: The use of mixed effect models with a specific functional form such as the Sigmoidal Mixed Model and the Piecewise Mixed Model (or Changepoint Mixed Model) with abrupt or smooth random change allows the interpretation of the defined parameters to understand longitudinal trajectories. Currently, there are no interface R packages that can easily fit the Sigmoidal Mixed Model allowing the inclusion of covariates or incorporating recent developments to fit the Piecewise Mixed Model with random change.

Results: To facilitate the modeling of the Sigmoidal Mixed Model, and Piecewise Mixed Model with abrupt or smooth random change, we have created an R package called nlive.

Global Odds Model with Proportional Odds and Trend Odds Applied to Gross and Microscopic Brain Infarcts.

Medical and epidemiological researchers commonly study ordinal measures of symptoms or pathology. Some of these studies involve two correlated ordinal measures. There is often an interest in including both measures in the modeling.

State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer's Disease.

Type 2 diabetes mellitus (T2DM) is common and increasing in prevalence worldwide, with devastating public health consequences. While peripheral insulin resistance is a key feature of most forms of T2DM and has been investigated for over a century, research on brain insulin resistance (BIR) has more recently been developed, including in the context of T2DM and non-diabetes states. Recent data support the presence of BIR in the aging brain, even in non-diabetes states, and found that BIR may be a feature in Alzheimer's disease (AD) and contributes to cognitive impairment.

Neuropathologic correlates of cerebral microbleeds in community-based older adults.

Cerebral microbleeds (CMBs) appearing as hypointense foci on T*-weighted magnetic resonance images are small hemorrhages that have been linked to cognitive decline and increased mortality. However, the neuropathologic correlates of CMBs in community-based older adults are poorly understood. The present study investigated the association of age-related neuropathologies with CMBs in community-based older adults.

Genome-Wide Mapping Implicates 5-Hydroxymethylcytosines in Diabetes Mellitus and Alzheimer's Disease.

Background: Diabetes mellitus (DM) is a recognized risk factor for dementia. Because DM is a potentially modifiable condition, greater understanding of the mechanisms linking DM to the clinical expression of Alzheimer's disease dementia may provide insights into much needed dementia therapeutics.

Objective: In this feasibility study, we investigated DM as a dementia risk factor by examining genome-wide distributions of the epigenetic DNA modification 5-hydroxymethylcytosine (5hmC).

nlive: an R Package to facilitate the application of the sigmoidal and random changepoint mixed models.

Background: The use of mixed effect models with a specific functional form such as the Sigmoidal Mixed Model and the Piecewise Mixed Model (or Changepoint Mixed Model) with abrupt or smooth random change allow the interpretation of the defined parameters to understand longitudinal trajectories. Currently, there are no interface R packages that can easily fit the Sigmoidal Mixed Model allowing the inclusion of covariates or incorporate recent developments to fit the Piecewise Mixed Model with random change.

Results: To facilitate the modeling of the Sigmoidal Mixed Model, and Piecewise Mixed Model with abrupt or smooth random change, we have created an R package called nlive.

Stability and change in acculturation-related characteristics in older Latinos: Implications for culturally compatible ADRD research.

Introduction: Acculturation-related characteristics, that is, factors directly connected to culture and familial relationships, are associated with engaged research participation within Latino communities. Despite this, little empirical data exists on whether acculturation changes over time in older Latinos, which has potential implications for Alzheimer's disease and related dementias (ADRD) research study design including longer duration clinical trial implementation.

Methods: Self-identified Latinos ( = 222; mean age = 71, 76% female) participating in one of three ongoing longitudinal community-based cohort studies of aging who reported their nativity outside of the United States/District of Columbia (US/DC) contributed, on average, 4.

A Longitudinal Study of Acculturation in Context and Cardiovascular Health and Their Effects on Cognition Among Older Latino Adults.

Background We previously outlined the importance of considering acculturation within the context of older Latino adults' lived experience (ie, acculturation in context) to better capture contributors to cognitive aging. We now examine this conceptual framework as related to level of and change in cardiovascular health, and whether cardiovascular health modifies previously documented associations of acculturation in context with cognition. Methods and Results Acculturation in context data from 192 Latino participants without dementia at baseline (age ~70 years) were compiled into 3 separate composite scores: acculturation-related (nativity, language-, and social-based preferences), contextually related socioenvironmental (experiences of discrimination, social isolation, social networks), and familism-related (Latino-centric family ethos).