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Item The Association of Late Life Cognitive Activity with Healthcare and Financial Decision Making in Community-Dwelling, Non-Demented Older Adults(Elsevier, 2021) Glover, Crystal M.; Yu, Lei; Stewart, Christopher C.; Wilson, Robert S.; Bennett, David A.; Boyle, Patricia A.; Neurology, School of MedicineObjective: The purpose of this study was to test the hypothesis that late life cognitive activity is associated with decision-making in older adults and to examine whether this association varies by level of cognitive function. Design: This study employed a cross-sectional design. Setting: All data were collected in participants' community-based residences. Participants: Participants were 1,084 older adults (mean age = 81.05 years, standard deviation = 7.53) without dementia (median Mini-Mental State Examination score = 29, interquartile range = 27.86-30.00). Measurements: Participants completed assessments of late life cognitive activity, cognitive function, and decision-making. We used linear regression models to examine the associations of late life cognitive activity and cognitive function with decision-making. Results: In a regression model adjusted for age, gender, and education, more frequent late life cognitive activity was associated with better decision-making, as was higher cognitive function. Furthermore, in an additional model that included the interaction of late life cognitive activity and cognitive function, the interaction was significant, such that late life cognitive activity was most strongly associated with decision-making among participants with lower levels of cognitive function. Conclusion: Frequent engagement in late life cognitive activity may help maintain decision-making among older persons, particularly among those with lower levels of cognitive function.Item Associations of decision making abilities with blood pressure values in older adults(Wolters Kluwer, 2020-01-01) Lamar, Melissa; Wilson, Robert S.; Yu, Lei; Stewart, Christopher C.; Bennett, David A.; Boyle, Patricia A.; Neurology, School of MedicineObjectives: Decision making, key to successful aging, has implications for financial success, physical health, and well being. While poor decision making has been linked with increased risk of mortality, age-related cognitive decline, and dementia, less is known regarding its associations with chronic disease indicators. We investigated the associations of decision making with blood pressure (BP) values [i.e., SBP, mean arterial pressure (MAP), and pulse pressure (PP), separately] in a community-based cohort study of aging. Methods: Participants were 908 nondemented older adults (age ∼81 years; 75% women) from the Rush Memory and Aging Project. Decision making was measured using questions designed to simulate materials used in financial and healthcare settings in the real world and yielded a total score and domain-specific health and financial decision making scores. Two seated and one standing BP measurement were taken with all three contributing to average SBP, MAP that is, [SBP + (2 × DBP)]/3, and PP, that is, SBP − DBP. Participants were queried about hypertension status and antihypertension medications were visually inspected and coded. Participants also underwent medical history and cognitive assessments. Results: In separate multivariable linear regression models, total decision making scores were inversely associated with SBP, MAP, and PP after adjusting for age, sex, education, antihypertension medication use, diabetes, and cumulative cardiovascular disease burden (P values = 0.03). Decision making remained associated with these BP values after additional adjustment for global cognition. Conclusion: Poorer decision making is associated with higher BP values in nondemented older adults.Item Associations of Health and Financial Literacy with Mortality in Advanced Age(SpringerLink, 2020-05) Stewart, Christopher C.; Yu, Lei; Lamar, Melissa; Wilson, Robert S.; Bennett, David A.; Neurology, School of MedicineBackground: Health and financial literacy are central to older adults' well-being and financial standing, but the relation of literacy with mortality in advanced age remains unclear. Aims: To determine whether lower literacy, as reflected in measures of total literacy and subscales of health and financial literacy, was associated with an increased risk of mortality. Methods: Participants were 931 community-based older adults from the Rush Memory and Aging Project [age: mean (SD) = 80.9 (7.6), range 58.8-100.8], an ongoing, prospective observational cohort study of aging. Participants were without dementia at the time literacy was assessed. Proportional hazards models were used to determine whether literacy measures were associated with mortality. Results: During up to 8 years of follow-up, 224 (24.1% of 931) participants died. In models that adjusted for age, sex, and education, lower total, health, and financial literacy were each associated with an increased risk of mortality (total literacy: HR = 1.020, 95% CI 1.010-1.031, p < 0.001; health literacy: HR = 1.015, 95% CI 1.008-1.023, p < 0.001; financial literacy: HR = 1.013, 95% CI 1.003-1.023, p = 0.014). These associations persisted after additionally adjusting for income and indices of health status; however, only the association of lower health literacy with mortality persisted after further adjusting for a robust measure of global cognition. Discussion: We suspect that the current associations of lower literacy with mortality reflect the detrimental effect of early pathologic brain aging on literacy. Conclusions: Lower literacy, particularly lower health literacy, is associated with mortality in advanced age.Item Change in Decision-Making Analysis and Preferences in Old Age(Oxford University Press, 2023) Wilson, Robert S.; Yu, Lei; Stewart, Christopher C.; Bennett, David A.; Boyle, Patricia A.; Neurology, School of MedicineObjectives: To test the hypotheses that decision making ability declines in old age and that a higher level of cognitive reserve is associated with a reduced rate of decline. Methods: As part of an ongoing cohort study, 982 older adults without dementia at study enrollment completed measures of purpose in life and cognitive activity which were used as markers of cognitive reserve. At annual intervals thereafter, they completed 6 tests of decision making. Results: In a factor analysis of baseline decision making scores, 3 measures (financial/health literacy, financial/health decision making, scam susceptibility) loaded on an "analytic" factor and 3 (temporal discounting small stakes, temporal discounting large stakes, risk aversion) loaded on a "preferences" (for temporal discounting and avoiding risk) factor. During a mean of 4.7 years of follow-up (standard deviation = 2.9), analytic factor scores decreased (mean = 0.042-unit per year, standard error [SE] = 0.006, p < .001) and preferences factor scores increased (mean = 0.021-unit per year, SE = 0.006, p < .001), with a correlation of 0.13 (p < .001) between rates of change. Evidence of an association between cognitive reserve and decision making was mixed with purpose in life related to change in analytic decision making, whereas past (but not current) cognitive activity was related to change in decision making preferences. Discussion: Decision making analysis and preferences change over time in late life. Change over time in decision making components is relatively independent and differentially related to age and cognitive reserve.Item Childhood Socioeconomic Status Interacts with Cognitive Function to Impact Scam Susceptibility Among Community-Dwelling Older Adults(Taylor & Francis, 2023) Glover, Crystal M.; Yu, Lei; Stewart, Christopher C.; Wilson, Robert S.; Bennett, David A.; Lamar, Melissa; Boyle, Patricia A.; Neurology, School of MedicineObjectives: We examined whether childhood socioeconomic status (SES) is related to scam susceptibility in old age and tested the hypothesis that childhood SES interacts with cognitive function to impact scam susceptibility. Methods: This study employed a cross-sectional design. All data were collected in participants' community-based residences. Participants were 1071 older adults (mean age = 81.05 years, SD = 7.53) without dementia (median MMSE score = 28.29, IQR = 27.86-30.00). Participants completed assessments of childhood SES, cognitive function, and scam susceptibility. We used linear regression models to examine the associations of childhood SES and cognitive function with scam susceptibility. Results: In a regression model adjusted for age, gender, and education, poorer cognitive function was associated with higher scam susceptibility, but childhood SES was not. However, in an additional model that included the interaction of childhood SES and cognitive function, the interaction was significant, such that lower childhood SES was associated with higher scam susceptibility among participants with lower cognitive function. Conclusion: Lower childhood SES is associated with higher scam susceptibility among older adults with lower levels of cognitive function. Thus, older adults who experienced limited resources in childhood and have lower cognitive function may represent a specific group for interventions to increase scam awareness and prevent financial exploitation.Item Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning(Springer Nature, 2022) Lahti, Jari; Tuominen, Samuli; Yang, Qiong; Pergola, Giulio; Ahmad, Shahzad; Amin, Najaf; Armstrong, Nicola J.; Beiser, Alexa; Bey, Katharina; Bis, Joshua C.; Boerwinkle, Eric; Bressler, Jan; Campbell, Archie; Campbell, Harry; Chen, Qiang; Corley, Janie; Cox, Simon R.; Davies, Gail; De Jager, Philip L.; Derks, Eske M.; Faul, Jessica D.; Fitzpatrick, Annette L.; Fohner, Alison E.; Ford, Ian; Fornage, Myriam; Gerring, Zachary; Grabe, Hans J.; Grodstein, Francine; Gudnason, Vilmundur; Simonsick, Eleanor; Holliday, Elizabeth G.; Joshi, Peter K.; Kajantie, Eero; Kaprio, Jaakko; Karell, Pauliina; Kleineidam, Luca; Knol, Maria J.; Kochan, Nicole A.; Kwok, John B.; Leber, Markus; Lam, Max; Lee, Teresa; Li, Shuo; Loukola, Anu; Luck, Tobias; Marioni, Riccardo E.; Mather, Karen A.; Medland, Sarah; Mirza, Saira S.; Nalls, Mike A.; Nho, Kwangsik; O'Donnell, Adrienne; Oldmeadow, Christopher; Painter, Jodie; Pattie, Alison; Reppermund, Simone; Risacher, Shannon L.; Rose, Richard J.; Sadashivaiah, Vijay; Scholz, Markus; Satizabal, Claudia L.; Schofield, Peter W.; Schraut, Katharina E.; Scott, Rodney J.; Simino, Jeannette; Smith, Albert V.; Smith, Jennifer A.; Stott, David J.; Surakka, Ida; Teumer, Alexander; Thalamuthu, Anbupalam; Trompet, Stella; Turner, Stephen T.; van der Lee, Sven J.; Villringer, Arno; Völker, Uwe; Wilson, Robert S.; Wittfeld, Katharina; Vuoksimaa, Eero; Xia, Rui; Yaffe, Kristine; Yu, Lei; Zare, Habil; Zhao, Wei; Ames, David; Attia, John; Bennett, David A.; Brodaty, Henry; Chasman, Daniel I.; Goldman, Aaron L.; Hayward, Caroline; Ikram, M. Arfan; Jukema, J. Wouter; Kardia, Sharon L.R.; Lencz, Todd; Loeffler, Markus; Mattay, Venkata S.; Palotie, Aarno; Psaty, Bruce M.; Ramirez, Alfredo; Ridker, Paul M.; Riedel-Heller, Steffi G.; Sachdev, Perminder S.; Saykin, Andrew J.; Scherer, Martin; Schofield, Peter R.; Sidney, Stephen; Starr, John M.; Trollor, Julian; Ulrich, William; Wagner, Michael; Weir, David R.; Wilson, James F.; Wright, Margaret J.; Weinberger, Daniel R.; Debette, Stephanie; Eriksson, Johan G.; Mosley, Thomas H., Jr.; Launer, Lenore J.; van Duijn, Cornelia M.; Deary, Ian J.; Seshadri, Sudha; Räikkönen, Katri; Radiology and Imaging Sciences, School of MedicineUnderstanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.Item Healthcare and Financial Decision Making and Incident Adverse Cognitive Outcomes among Older Adults(Wiley, 2019-08) Stewart, Christopher C.; Yu, Lei; Wilson, Robert S.; Bennett, David A.; Boyle, Patricia A.; Neurology, School of MedicineOBJECTIVES To determine if poorer healthcare and financial decision making forecasts adverse cognitive outcomes in old age. Specifically, we hypothesized that poorer decision making would be associated with an increased risk of incident Alzheimer's dementia, an increased risk of incident mild cognitive impairment (MCI), and a more rapid decline in cognition. DESIGN An ongoing prospective observational cohort study of aging (the Rush Memory and Aging Project). SETTING The greater Chicago area. PARTICIPANTS A total of 952 community‐based older adults without dementia at baseline. MEASUREMENTS Participants completed a measure of healthcare and financial decision making at baseline and underwent annual standardized evaluations to track clinical status and cognitive functions (global cognition, episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability). RESULTS During up to 9 years of follow‐up (M = 5.2 y; standard deviation = 2.7), 156 participants developed Alzheimer's dementia (16.4% of 952), 253 participants developed MCI (33.2% of 760), and each cognitive measure declined (all P s < .001). In Cox proportional hazards models adjusted for age, sex, and education, poorer decision making was associated with an increased risk of incident Alzheimer's dementia (hazard ratio [HR] = 1.17; 95% confidence interval [CI] = 1.10‐1.24; P < .001) and incident MCI (HR = 1.16; 95% CI = 1.10‐1.22; P < .001). Further, in linear mixed‐effects models, poorer decision making among those who were initially free of cognitive impairment was associated with a more rapid decline in global cognition and four of five specific cognitive domains (all P s < .05). CONCLUSION Our results suggest that poorer healthcare and financial decision making heralds adverse cognitive outcomes in old age.Item Latin Dance and Working Memory: The Mediating Effects of Physical Activity Among Middle-Aged and Older Latinos(Frontiers, 2022-04-15) Aguiñaga, Susan; Kaushal, Navin; Balbim, Guilherme M.; Wilson, Robert S.; Wilbur, JoEllen E.; Hughes, Susan; Buchner, David M.; Berbaum, Michael; McAuley, Edward; Vásquez, Priscilla M.; Marques, Isabela G.; Wang, Tianxiu; Marquez, David X.; Health Sciences, School of Health and Human SciencesBackground Physical activity (PA) is a promising method to improve cognition among middle-aged and older adults. Latinos are at high risk for cognitive decline and engaging in low levels of PA. Culturally relevant PA interventions for middle-aged and older Latinos are critically needed to reduce risk of cognitive decline. We examined changes in cognitive performance among middle-aged and older Latinos participating in the BAILAMOS™ dance program or a health education group and compared the mediating effects of PA between group assignment and change in cognitive domains. Methods Our 8-month randomized controlled trial tested BAILAMOS™, a 4-month Latin dance program followed by a 4-month maintenance phase. A total of 333 older Latinos aged 55+ were randomized to either BAILAMOS™, or to a health education control group. Neuropsychological tests were administered, scores were converted to z-scores, and specific domains (i.e., executive function, episodic memory, and working memory) were derived. Self-reported PA was assessed, and we reported categories of total PA, total leisure PA, and moderate-to-vigorous PA as minutes/week. A series of ANCOVAs tested changes in cognitive domains at 4 and 8 months. A mediation analysis tested the mediating effects of each PA category between group assignment and a significant change in cognition score. Results The ANCOVAs found significant improvement in working memory scores among participants in the dance group at month 8 [F(1,328) = 5.79, p = 0.017, d = 0.20], but not in executive functioning [F(2,328) = 0.229, p = 0.80, Cohen’s d = 0.07] or episodic memory [F(2,328) = 0.241, p = 0.78, Cohen’s d = 0.05]. Follow-up mediation models found that total PA mediated the relationship between group assignment and working memory, in favor of the dance group (β = 0.027, 95% CI [0.0000, 0.0705]). Similarly, total leisure PA was found to mediate this relationship [β = 0.035, 95% CI (0.0041, 0.0807)]. Conclusion A 4-month Latin dance program followed by a 4-month maintenance phase improved working memory among middle-aged and older Latinos. Improvements in working memory were mediated by participation in leisure PA. Our results support the current literature that leisure time PA influences cognition and highlight the importance of culturally relevant PA modalities for Latinos. Clinical Trial Registration [www.ClinicalTrials.gov], identifier [NCT01988233].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 Polygenic risk score penetrance & recurrence risk in familial Alzheimer disease(Wiley, 2023) Qiao, Min; Lee, Annie J.; Reyes-Dumeyer, Dolly; Tosto, Giuseppe; Faber, Kelley; Goate, Alison; Renton, Alan; Chao, Michael; Boeve, Brad; Cruchaga, Carlos; Pericak-Vance, Margaret; Haines, Jonathan L.; Rosenberg, Roger; Tsuang, Debby; Sweet, Robert A.; Bennett, David A.; Wilson, Robert S.; Foroud, Tatiana; Mayeux, Richard; Vardarajan, Badri N.; Medical and Molecular Genetics, School of MedicineObjective: To compute penetrance and recurrence risk using a genome-wide PRS (including and excluding the APOE region) in families with Alzheimer's disease. Methods: Genotypes from the National Institute on Aging Late-Onset Alzheimer's Disease Family-Based Study and a study of familial Alzheimer's disease in Caribbean Hispanics were used to compute PRS with and without variants in the 2 MB region flanking APOE. PRS was calculated in using clumping/thresholding and Bayesian methods and was assessed for association with Alzheimer's disease and age at onset. Penetrance and recurrence risk for carriers in highest and lowest PRS quintiles were compared separately within APOE-ε4 carriers and non-carriers. Results: PRS excluding the APOE region was strongly associated with clinical and neuropathological diagnosis of AD. PRS association with AD was similar in participants who did not carry an APOE-ε4 allele (OR = 1.74 [1.53-1.91]) compared with APOE-ε4 carriers (1.53 [1.4-1.68]). Compared to the lowest quintile, the highest PRS quintile had a 10% higher penetrance at age 70 (p = 0.0006) and a 20% higher penetrance at age 80 (p < 10e-05). Stratifying by APOE-ε4 allele, PRS in the highest quintile was significantly more penetrant than the lowest quintile, both, within APOE-ε4 carriers (14.5% higher at age 80, p = 0.002) and non-carriers (26% higher at 80, p < 10e-05). Recurrence risk for siblings conferred by a co-sibling in the highest PRS quintile increased from 4% between the ages of 65-74 years to 39% at age 85 and older. Interpretation: PRS can be used to estimate penetrance and recurrence risk in familial Alzheimer's disease among carriers and non-carries of APOE-ε4.