Immune cell counts in cerebrospinal fluid predict cognitive function in aging and neurodegenerative disease

IntroductionImmune dysfunction is important in aging and neurodegeneration; lacking clinically available tools limits research translation. We tested associations of cerebral spinal fluid (CSF) monocyte-to-lymphocyte ratio (MLR)-innate immune activation surrogate-with cognition in an aging and dementia cohort, hypothesizing that elevated MLR is associated with poorer executive functioning.MethodsCSF MLR was calculated in well-characterized, genotyped participants enrolled in studies of aging and dementia at University of California, San Francisco Memory and Aging Center (n = 199, mean age 57.5 years, SD 11.9). Linear models tested associations with episodic memory and executive function (verbal fluency, speeded set-shifting).ResultsAging was associated with higher CSF monocyte, lower lymphocyte counts, and higher MLRs (p < 0.001). MLR was associated with verbal fluency (p < 0.05) only.DiscussionUsing clinical labs, we show an inverse association between CSF MLR and executive function in aging and dementia, supporting the utility of clinical labs in capturing associations between innate immune dysfunction and neurodegeneration

Sex-Related Differences in the Relationship Between β-Amyloid and Cognitive Trajectories in Older Adults

Objective: We aimed to test the hypothesis that elevated neocortical β-amyloid (Aβ), a hallmark feature of Alzheimer's disease (AD), predicts sex-specific cognitive trajectories in clinically normal older adults, with women showing greater risk of decline than men. Method: Florbetapir Aβ positron emission tomography (PET) was acquired in 149 clinically normal older adults (52% female, Mage = 74). Participants underwent cognitive testing at baseline and during annual follow-up visits over a timespan of up to 5.14 years. Mixed-effects regression models evaluated whether relations between baseline neocortical Standardized Uptake Value Ratio (SUVR) and composite scores of episodic memory, executive functioning, and processing speed were moderated by sex (male/female) and apolipoprotein E (APOE) status (ε4 carrier/noncarrier). Results: Higher baseline SUVR was associated with longitudinal decline in episodic memory in women (b = -1.32, p < .001) but not men (b = -0.30, p = .28). Female APOE ε4 carriers with elevated SUVR showed particularly precipitous declines in episodic memory (b = -4.33, p < .001) whereas other cognitive domains were spared. SUVR did not predict changes in executive functioning or processing speed, regardless of sex (ps >.63), though there was a main effect of SUVR on processing speed (b = 2.50, p = .003). Conclusions: Clinically normal women with elevated Aβ are more vulnerable to episodic memory decline than men. Understanding sex-related differences in AD, particularly in preclinical stages, is crucial for guiding precision medicine approaches to early detection and intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

The Relationship between Cognitive Reserve and Functional Ability is Mediated by Executive Functioning in Older Adults

© 2015 Taylor & Francis. It has been noted in the literature that cognitive reserve (CR) predicts future functional ability (FA), but the association between CR and current FA is rather limited. This investigation aimed to explicate this relationship, and hypothesized it would be mediated by executive functioning (EF). To best understand the relationship between CR and FA, we recruited and tested independent community-dwelling older adults (OAs). Bivariate correlations and hierarchical regressions were completed to determine the association between CR and FA. Both individual CR measures and a composite CR score were used. Mediation analyses were completed to examine our hypothesis that EF would mediate the CR and FA relationship. All measures of CR were positively related to and predictive of FA. Although the highest zero-order correlation across the independent CR proxies was between income and FA (r =.417), education accounted for the greatest amount of variance in FA, 8.3% after controlling for age and Mini-Mental State Examination performance. Furthermore, the CR composite had a higher correlation (r =.447) and accounted for more variance than any of the independent proxies. Complete mediation was found between a CR composite and FA via an internally consistent D-KEFS composite score (Cronbachs =.795). This suggests that as CR increases so does EF, which in turn improves FA. Thus, future investigations could determine the effect on FA in OAs by improving EF