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Item 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 MedicineBackground 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.Item 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 MedicineCognitive 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.