Browsing by Subject "Reserve"

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    Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer’s Disease
    (Elsevier, 2021) Pichet Binette, Alexa; Vachon-Presseau, Étienne; Morris, John; Bateman, Randall; Benzinger, Tammie; Collins, D. Louis; Poirier, Judes; Breitner, John C. S.; Villeneuve, Sylvia; Dominantly Inherited Alzheimer Network (DIAN); PREVENT-AD Research Group; Psychiatry, School of Medicine
    Background: Major prevention trials for Alzheimer's disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods: A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results: In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions: In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.
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    Loneliness Interacts With Cognition in Relation to Healthcare and Financial Decision Making Among Community-Dwelling Older Adults
    (Oxford University Press, 2020-11-23) Stewart, Christopher C.; Yu, Lei; Glover, Crystal M.; Mottola, Gary; Bennett, David A.; Wilson, Robert S.; Boyle, Patricia A.; Neurology, School of Medicine
    Background and objectives: Cognition is a known determinant of healthcare and financial decision making in old age. Social vulnerabilities also might play a role in such decisions; however, the evidence for this is less clear. Here, we examined the association of loneliness with decision making and tested the hypothesis that loneliness is associated with decision making via its interaction with global cognition. Research design and methods: Participants were 1,121 nondemented older adults from the Rush Memory and Aging Project. Healthcare and financial decision making was assessed via a performance-based measure; loneliness was assessed via the De Jong Gierveld Loneliness Scale; and cognition was assessed via a 19-test neuropsychological battery. Results: In a regression model adjusted for age, sex, and education, global cognition was associated with decision making (B = 2.43, SE = 0.14, p < .001) but loneliness was not (B = -0.04, SE = 0.11, p = .72). However, in a model including the interaction of loneliness with global cognition, the interaction was significant (B = 0.44, SE = 0.20, p = .03), such that the detrimental effect of loneliness on decision making was stronger when cognition was low. In secondary analyses examining the interaction of loneliness with 5 specific cognitive domains, the interaction between loneliness and working memory with decision making was significant (B = 0.35, SE = 0.15, p = .02). Discussion and implications: Our results suggest that loneliness compromises healthcare and financial decision making among older adults with lower global cognition and, more specifically, lower working memory.
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    Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease
    (Oxford University Press, 2021) Ewers, Michael; Luan, Ying; Frontzkowski, Lukas; Neitzel, Julia; Rubinski, Anna; Dichgans, Martin; Hassenstab, Jason; Gordon, Brian A.; Chhatwal, Jasmeer P.; Levin, Johannes; Schofield, Peter; Benzinger, Tammie L.S; Morris, John C.; Goate, Alison; Karch, Celeste M.; Fagan, Anne M.; McDade, Eric; Allegri, Ricardo; Berman, Sarah; Chui, Helena; Cruchaga, Carlos; Farlow, Marty; Graff-Radford, Neill; Jucker, Mathias; Lee, Jae-Hong; Martins, Ralph N.; Mori, Hiroshi; Perrin, Richard; Xiong, Chengjie; Rossor, Martin; Fox, Nick C.; O’Connor, Antoinette; Salloway, Stephen; Danek, Adrian; Buerger, Katharina; Bateman, Randall J.; Habeck, Christian; Stern, Yaakov; Franzmeier, Nicolai; Alzheimer’s Disease Neuroimaging Initiative; Dominantly Inherited Alzheimer Network; Neurology, School of Medicine
    Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal ageing, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer's disease. Using resting-state functional MRI, we assessed both resting-state functional MRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: (i) 108 individuals with autosomal dominantly inherited Alzheimer's disease and 71 non-carrier controls; and (ii) 156 amyloid-PET-positive subjects across the spectrum of sporadic Alzheimer's disease and 184 amyloid-negative controls. In the autosomal dominant Alzheimer's disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer's sample, disease stage was assessed by temporal lobe tau-PET (i.e. composite across Braak stage I and III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer's disease, we found higher functional MRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (P = 0.007). Similarly, for patients with sporadic Alzheimer's disease, higher functional MRI-assessed system segregation was associated with less decrement in global cognition (P = 0.001) and episodic memory (P = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer's disease.