55 Sleep Quality, Tau Burden, and Memory in Older Women with Higher Alzheimer’s Disease Risk
Authors: Lui Kitty K , Shepherd Alyx L , Wang Xin , Bernier Rachel A , Chowdhury Tasnuva , Bosompra Naa-Oye , DeYoung Pamela , Malhotra Atul , Sundermann Erin E , Banks Sarah J 
Published: December 2023

Objective:

Compared to older men, Alzheimer’s Disease (AD) is more common in older women, who present with higher levels of pathological tau and accelerated memory decline, although it is unclear why. Furthermore, sleep complaints increase with age, with older women reporting worse sleep quality than older men, and past studies have linked sleep disturbances to tau. Because of the life-long “verbal memory advantage” in women over men, nonverbal memory may more accurately reflect tau burden in women since sex differences are not as apparent. Here, in a sample of older women in the Women Inflammation Tau Study (WITS), we examined the associations between subjective sleep quality, tau in temporal regions, and memory, and whether tau would be more strongly related to nonverbal memory than verbal memory.

Participants and Methods:

In WITS, women have elevated AD polygenic hazard scores and have mild cognitive impairment as indicated by the telephone Montreal Cognitive Assessment (range:13-20). This preliminary sample of 20 women (aged 72.0±3.7) completed the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality in 7 domains of sleep health over the past month. A global score (range:0-21) is calculated, with a score >5 indicative of being a poor sleeper. Participants also underwent positron emission tomography (PET) with the 18F-MK6240 tracer and T1-weighted magnetic resonance imagining (MRI) to determine tau deposition. Standardized uptake value ratio (SUVR) was calculated using the inferior cerebellum grey matter as the reference region, which was created from Automated Anatomic Labeling atlas in native T1 space. The region of interest (ROI) was a composite meta-temporal region. The Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory (LM) Story A and B were administered to assess verbal memory. The Brief Visuospatial Memory Test-Revised (BVMT-R) was administered to assess nonverbal memory. Analysis focused on the delayed recall scores from the memory tests. Partial correlation was used to analyze the associations between PSQI global score, tau-PET SUVR in meta-temporal ROI, and memory delayed recall scores, while adjusting for age and education years.

Results:

8 women were poor sleepers indicated by the PSQI global score (mean:4.9±2). Worse subjective sleep quality was associated with greater tau in meta-temporal ROI (r=0.63, p=0.005) and lower BVMT-R delayed recall (r=-0.46, p=0.05). Sleep quality was not significantly related to either RAVLT or LM delayed recall (all p’s>0.40). Tau in meta-temporal ROI was not significantly associated with nonverbal (p=0.23) or verbal memory (all p’s>0.40) delayed recall.

Conclusions:

In this preliminary analysis, subjective sleep quality was linked to temporal tau deposition and nonverbal memory delayed recall, which may suggest that poor sleep exacerbates pathogenesis of tau that leads to memory difficulties in older women at increased risk for AD. Although tau was not significantly related to any memory measures, we will explore whether tau will mediate or moderate the relationship between sleep quality and nonverbal memory once we are powered to do so. Continual evaluation and treatment of sleep may be imperative in mitigating AD risk, especially for older women, however, future longitudinal studies will be necessary to investigate this.