Developing Topics.

Background: Despite evidence that Alzheimer's disease (AD) is highly heritable, there remains substantial "missing" heritability, likely due in part to the effect of rare variants and to the past reliance on case-control analysis. Here, we leverage powerful endophenotypes of AD (cognitive performance across multiple cognitive domains) in a rare variant analysis to identify novel genetic drivers of cognition in aging and disease.

Method: We leveraged 8 cohorts of cognitive aging with whole genome sequencing data from the AD Sequencing Project to conduct rare variant analyses of multiple domains of cognition (N = 9,317; mean age = 73; 56% female; 52% cognitively unimpaired).

Developing Topics.

Background: Previous models of resilience to Alzheimer's Disease (AD) have relied on cross-sectional designs and inclusion of measures of neuropathology. Here, we present a novel modeling approach incorporating longitudinal data and the use of APOE and higher order interaction terms to approximate neuropathological resilience, vastly increasing participant diversity and statistical power. We validate this approach and report novel genetic associations with neuropathological resilience.

Drug Development.

Background: Genome-wide association studies (GWAS) have identified close to one hundred loci associated with Alzheimer's disease (AD) risk. However, for most of these loci we do not understand the underlying mechanism leading to disease. Crispr genome editing in human induced pluripotent stem cells (hiPSCs) provides a model system to study the effects of these genetic variants in a disease relevant cell type.

Dementia Care Practice.

Background: The Medication Review in Cognitive Impairment and Dementia (MedRevCiD) checklist is a new tool designed to assist health care professionals in optimizing medication use in individuals with Mild Cognitive Impairment (MCI) or dementia. It consists of 6 domains, each of which addresses a specific medication use issue such as medication management and adherence. The primary objective of this study was to compare the mean number of drug-related problems (DRPs) identified with MedRevCiD Checklist to the Medication Appropriateness Index (MAI) in older adults attending a primary care-based memory clinic.

Dementia Care Practice.

Background: The use of potentially inappropriate medications (PIMs) in older adults with dementia and/or Mild Cognitive Impairment (MCI) has been associated with increased adverse events, drug-related problems (DRPs), prolonged hospitalization, risk of falls, and increased length of stay. This study aimed to identify which explicit tool, Beers criteria 2023 or Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) 2023, identifies more PIM use among older adults with MCI or dementia.

Methods: A cross-sectional study was conducted at a Multispecialty Interprofessional Team-based (MINT) memory clinic.