Sleep contributes to memory retention and recall. Alzheimer’s disease (AD) patients experience decreased slow wave activity (SWA) during sleep. This decrease in SWA is associated with impaired memory consolidation (Lee et al., 2020). Long-term forgetting (LTF) over days or weeks has been linked to memory consolidation deficits and has been suggested as an early marker of AD that could be useful for identifying at-risk individuals for preclinical AD trials (Weston et al., 2018). Here, we examined associations between LTF and SWA in a sample of Presenilin-1 (PSEN1) E280A mutation carriers with autosomal dominant Alzheimer’s disease and non-carrier family members. Carriers of this mutation usually develop dementia in their forties (Fuller et al., 2019).

Fourteen cognitively unimpaired PSEN1-E280A mutation carriers and sixteen age-matched non-carriers (mean age: 34.2 years) from the Colombia-Boston (COLBOS) biomarker study were included. Participants completed an overnight polysomnogram (PSG) and memory testing (NEUROPSI Word List) at 3-time points: 1) the night before PSG: immediate recall (Day1-ImmRecall) and a 20-minute delayed recall (Day1-DelayedRecall), 2) recall the following day (Day2-recall), and 3) recall one week later (Day7-recall). SWA was measured as the ratio 0. 6-1Hz/0.6-4Hz in frontopolar and frontotemporal regions and was calculated for sleep stages N2+N3 (slow wave sleep) based on an automated staging algorithm. Each participant’s LTF was calculated as the percent retention between Day 1 immediate recall and Day 7 recall (Butler, 2009). Mann-Whitney U tests were used to compare differences in recall, SWA, and LTF between groups. Spearman’s correlation was used to examine the associations between memory recall at different time points and SWA, as well as between LTF and SWA.

On Day 1, carriers had lower performance in immediate recall (p=0.02), compared to non-carriers, but there were no group differences in the 20-minute delayed recall. Carriers also recalled fewer words on Day 2 (p=0.03) and Day 7 (p=0.009) and had greater LTF (p=0.03). There were no group differences in SWA. In our overall sample, worse performance on word list delayed recall on Day 1, Day 2, and Day 7 was associated with less SWA across both frontotemporal (Day1: p=0.04, Day2: p=0.02, Day7: p=0.02) and frontopolar (all Ps<0.01) regions. In carriers, only worse performance on Day 1 delayed recall was associated with lower SWA in the frontopolar region (r= 0.535; p=0.049). Memory recall on other days was not associated with SWA in any brain regions. Additionally, greater LTF was associated with less SWA across both frontopolar (r= 0.507; p=0.005) and frontotemporal regions (r= 0.463 p= 0.01).

Preliminary findings suggest that long-term forgetting is associated with less slow- wave activity in preclinical autosomal dominant Alzheimer’s disease. These results also suggest that SWA may be related to pre-sleep learning and subsequent overnight memory consolidation processes. LTF testing may be useful in selecting individuals for preclinical AD trials. Future research on the impact of slow wave activity on LTF may be useful in identifying ways to enhance short- and long-term memory consolidation in individuals at greater risk for dementia.

Physical inactivity is associated with a greater risk of frailty, neuropsychiatric symptoms, worse quality of life, and increased risk for Alzheimer’s disease. Little is known about how physical activity engagement of older adults during the COVID-19 pandemic relates to subjective cognitive concerns and management of emotional distress. This study aimed to examine whether there were changes in physical activity during the pandemic in older adults at baseline and 3 months compared to before the pandemic and whether these changes varied based on age, sex, income level, and employment status. Further, we examined whether individuals who reported engaging in less physical activity experienced greater subjective cognitive difficulties and symptoms of depression and anxiety than those who maintained or increased their physical activity levels.

301 participants (73% non-Hispanic whites) completed an online survey in either English or Spanish between May and October 2020 and 3 months later. The Everyday Cognition Scale was used to measure subjective cognitive decline, the CES-D-R-10 scale to measure depressive symptoms, and the GAD-7 scale to measure anxiety symptoms. Changes in physical activity were measured with the question “Since the coronavirus disease pandemic began, what has changed for you or your family in regard to physical activity or exercise levels?” with options “less physical activity,” “increase in physical activity,” or “same activity level.” Income was self-reported as high, middle, or low. Analyses of chi-squared tests were used to examine differences in physical activity maintenance by age, income level, sex, and employment status.

Most individuals (60%) reported having decreased their physical activity levels during the pandemic, at baseline and 3-month followup. There were differences in physical activity levels based on income and age: participants with a high income reported engaging in more physical activity than those with low income (X^2=4.78, p =.029). At the 3-month follow-up, middle-income participants reported being less active than the high-income earners (X^2=8.92, p=.003), and younger participants (55-65 years, approximately) reported being less active than older participants (X^2=5.28, p =.022). Those who reported an increase in their physical activity levels had fewer cognitive concerns compared to those who were less active at baseline, but this difference was not seen in the 3-month follow-up. Participants of all ages who reported having maintained or increased their physical activity levels had fewer depressive symptoms than those who were less active (p < 0.0001). Those who reported maintaining their physical activity levels exhibited fewer anxiety symptoms than those who were less active (p < 0.01).

Older adults reported changes in physical activity levels during the pandemic and some of these changes varied by sociodemographic factors. Further, maintaining physical activity levels was associated with lower symptoms of depression, anxiety, and cognitive concerns. Encouraging individuals and providing resources for increasing physical activity may be an effective way to mitigate some of the pandemic’s adverse effects on psychological wellbeing and may potentially help reduce the risk for cognitive decline. Alternately, it is possible that improving emotional distress could lead to an increase in physical activity levels and cognitive health.

Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance.

We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education.

Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory.

Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.