Grey matter ageing-related tau astrogliopathy: associations with brain pathologies and cognitive decline.

Grey matter ARTAG pathology is common in aged brains and detected in multiple brain regions. However, the associations of grey matter ARTAG with Alzheimer's disease (AD) and other common age-related proteinopathies, as well as clinical phenotypes including Alzheimer's dementia and cognitive decline remain unclear. We examined 442 decedents (mean age-at-death=90 years, males=32%) from three longitudinal community-based clinical-pathological studies. Using AT8 immunohistochemistry, grey matter ARTAG pathology was counted in the the superior frontal, anterior temporal tip, and amygdala and summarized as a severity score from 0 (none) to 6 (severe). AD and other common age-related neuropathologies were also evaluated. The diagnosis of Alzheimer's dementia was based on clinical evaluations; annual tests of cognitive performance were summarized as global cognition and five cognitive domains. Multivariable logistic regression tested the associations of grey matter ARTAG pathology with an array of age-related neuropathologies. To evaluate associations of grey matter ARTAG pathology with Alzheimer's dementia and cognitive decline, we employed logistic regression and linear mixed effect models. Grey matter ARTAG pathology was seen in 324 (73%) participants, of which 303 (68%) participants had ARTAG in the amygdala, 246 (56%) in the anterior temporal tip, and 137 (31%) in the superior frontal region. Grey matter ARTAG pathology from each of the three regions was associated with pathologic diagnosis of AD and LATE-NC but not with vascular pathology. In fully adjusted models that controlled for demographics, AD, and common age-related pathologies, an increase in severity of grey matter ARTAG pathology in the superior frontal cortex, but not in the amygdala or the anterior temporal tip, was associated with higher odds of Alzheimer's dementia and faster decline in global cognition, episodic memory, and semantic memory. These results provide compelling evidence that grey matter ARTAG, specifically in the superior frontal cortex contributes to Alzheimer's dementia and cognitive decline in old age.

Factors Associated With Healthcare and Financial Decision Making Among Older Black Adults Without Dementia.

OBJECTIVES: The study aims to identify factors associated with health care and financial decision-making among older Black adults without dementia. METHODS: Participants (N = 326) underwent assessments of decision-making and completed measurements of factors from four categories: cognitive, contextual, psychosocial, and personality. We performed separate linear regression models to examine the association between each factor and decision-making and created a fully adjusted model. RESULTS: Higher global cognition (estimate = 1.92, SE = 0.21, p < .0001) was associated with better decision-making. Contextual factors including higher current annual income (estimate = 0.23, SE = 0.05, p < .0001), higher childhood socioeconomic status (estimate = 0.48, SE = 0.18, p = .006), higher health and financial literacy (estimate = 0.08, SE = 0.01, p < .0001), and lower financial stress (estimate = -0.19, SE = 0.07, p = .01) were associated with better decision-making. More psychological well-being (estimate = 0.07, SE = 0.22, p = .001), a psychosocial factor, and less neuroticism (estimate = -0.06, SE = 0.02, p = .002), a personality factor, were associated with better decision-making. In the fully adjusted model, two factors, higher global cognition and higher literacy (health and financial), remained associated with better decision-making. CONCLUSIONS: Cognitive and contextual factors serve as drivers of decision-making among older Black adults. CLINICAL IMPLICATIONS: Clinicians may implement strategies to bolster cognition and improve health and financial literacy to facilitate optimal decision-making among older Black adults.

Health and Financial Literacy and the Acquisition of COVID-19 Knowledge in Older Adults.

Knowledge about COVID-19 enters into many aspects of decision making, especially for older people who are at increased risk of severe disease or death. Yet little is known about the resources that supported older people's uptake of COVID-19 knowledge. Here, we hypothesized that higher pre-pandemic health and financial literacy was associated with higher COVID-19 knowledge. Participants were 434 community-based older people without dementia. COVID-19 knowledge was assessed via a 5-item measure, and health and financial literacy was assessed via a 32-item measure. In an ordinal regression model adjusted for age, gender, and education, higher literacy was associated with higher COVID-19 knowledge (p < .0001), and this association persisted after further adjusting for robust measures of global cognition or one of five specific cognitive domains (all p's ≤ .0001). These findings suggest that literacy plays a key role in supporting older people's acquisition of impactful knowledge in the real world.

Longer time horizons are associated with reduced risk of mortality and disability in older adults.

OBJECTIVES: Longer time horizons are associated with positive health behaviors, but the associations of time horizons with disability and mortality are less understood. This study aims to test the hypothesis that longer time horizons are associated with decreased disability and mortality in older adults. METHOD: Participants were 1052 older adults (mean age = 81 ± 7 years) without dementia. Proportional hazard models adjusted for age, sex, and education were used to examine the associations of time horizons with risk of mortality and disability. RESULTS: During up to 11 years of follow up (mean = 5.7), 317 participants died. In fully adjusted models, longer time horizons were associated with reduced mortality risk (hazard rate [HR] = 0.78, 95% confidence interval [CI] = 0.68-0.89). About 36.7% of participants developed disability in instrumental activities of daily living (ADLs) and 49.3% developed disability in basic ADLs during follow up. Longer time horizons were associated with a reduced risk of disability in basic ADLs (HR = 0.89, 95% CI = 0.79-0.99) but not instrumental ADLs (HR = 0.90, 95% CI = 0.80-1.03). CONCLUSION: Longer time horizons are associated with a reduced risk of all-cause mortality and disability in basic ADLs among community-dwelling older adults, thus highlighting a potentially modifiable psychological risk factor for negative health outcomes in aging.

MRI-Derived AD Signature of Cortical Thinning and Plasma P-Tau217 for Predicting Alzheimer Dementia Among Community-Dwelling Older Adults.

Background and Objectives: Structural brain MRI and blood-based phosphorylated tau (p-tau) measures are among the least invasive and least expensive Alzheimer's disease (AD) biomarkers to date. The extent to which these biomarkers may outperform one another in predicting future Alzheimer dementia diagnosis is poorly understood, however. This study investigated 2 specific AD biomarkers, i.e., a cortical thickness signature of AD (AD-CT) and plasma p-tau217, for predicting Alzheimer dementia. Methods: Data came from community-dwelling older participants of the Religious Orders Study or the Rush Memory and Aging Project. AD-CT was obtained from 3T MRI scans using a magnetization-prepared rapid acquisition gradient echo sequence and by averaging thickness from previously identified cortical regions implicated in AD. Plasma p-tau217 was quantified using an immunoassay developed by Lilly Research Laboratories on the MSD platform. Both MRI scans and blood specimens were collected at the same visits, and subsequent diagnoses of Alzheimer dementia were determined through annual detailed clinical evaluations. Cox proportional hazards models examined the associations of the 2 biomarkers with incident Alzheimer dementia, and prediction accuracy was assessed using c-statistics. Results: A total of 198 older adults, on average 84 years of age, were included. Over a mean follow-up of 4 years, 60 (30%) individuals developed Alzheimer dementia. AD-CT (hazard ratio: 1.71, 95% CI 1.26-2.31) and separately plasma p-tau217 (hazard ratio: 2.57, 95% CI 1.83-3.61) were associated with incident Alzheimer dementia. The c-statistic for prediction accuracy was consistently higher for plasma p-tau217 (between 0.74 and 0.81) than AD-CT (between 0.70 and 0.75) across a range of time horizons. Furthermore, with both biomarkers included in the same model, there was only modest improvement in the c-statistic due to AD-CT. Discussion: Plasma p-tau217 outperforms an imaging-based cortical thickness signature of AD in predicting future Alzheimer dementia diagnosis. Furthermore, the AD cortical thickness signature adds little to the prediction accuracy above and beyond plasma p-tau217.

Race/ethnicity and the measurement of cognition in NSHAP: Recommendations for robustness.

OBJECTIVES: In this study, we examine the measurement of cognition in different racial/ethnic groups to move towards a less biased and more inclusive set of measures for capturing cognitive change and decline in older adulthood. METHODS: We use data from Round 2 (N=3377) and Round 3 (N=4777) of the National Social Life, Health, and Aging Project (NSHAP) and examine the study's Survey Adjusted version of the Montreal Cognitive Assessment (MoCA-SA). We employ exploratory factor analyses to explore configural invariance by racial/ethnic group. Using modification indexes, two-parameter item response theory models, and split-sample testing, we identify items that seem robust to bias by race. We test the predictive validity of the full (18-item) and short (4-item) MoCA-SAs using self-reported dementia diagnosis, instrumental activities of daily living (IADLs), proxy reports of dementia, proxy reports of dementia-related death, and National Death Index reports of dementia-related death. RESULTS: We found that four measures out of the 18 used in NSHAP's MoCA-SA formed a scale that was more robust to racial bias. The shortened form predicted consequential outcomes as well as NSHAP's full MoCA-SA. The short form was also moderately correlated with the full form. DISCUSSION: Although sophisticated structural equation modeling techniques would be preferrable for assuaging measurement invariance by race in NSHAP, the shortened form of the MoCA-SA provides a quick way for researchers to carry out robustness checks and to see if the disparities and associations by race they document are "real" or the product of artifactual bias.

Association between hippocampal microglia, AD and LATE-NC, and cognitive decline in older adults.

INTRODUCTION: This study investigates the relationship between microglia inflammation in the hippocampus, brain pathologies, and cognitive decline. METHODS: Participants underwent annual clinical evaluations and agreed to brain donation. Neuropathologic evaluations quantified microglial burden in the hippocampus, amyloid beta (Aß), tau tangles, and limbic age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy neuropathologic changes (LATE-NC), and other common brain pathologies. Mixed-effect and linear regression models examined the association of microglia with a decline in global and domain-specific cognitive measures, and separately with brain pathologies. Path analyses estimated direct and indirect effects of microglia on global cognition. RESULT: Hippocampal microglia were associated with a faster decline in global cognition, specifically in episodic memory, semantic memory, and perceptual speed. Tau tangles and LATE-NC were independently associated with microglia. Other pathologies, including Aß, were not related. Regional hippocampal burden of tau tangles and TDP-43 accounted for half of the association of microglia with cognitive decline. DISCUSSION: Microglia inflammation in the hippocampus contributes to cognitive decline. Tau tangles and LATE-NC partially mediate this association.

Relative Contributions of Mixed Pathologies to Cognitive and Functional Symptoms in Brain Donors Exposed to Repetitive Head Impacts.

OBJECTIVE: Exposure to repetitive head impacts (RHI) is associated with later-life cognitive symptoms and neuropathologies, including chronic traumatic encephalopathy (CTE). Cognitive decline in community cohorts is often due to multiple pathologies; however, the frequency and contributions of these pathologies to cognitive impairment in people exposed to RHI are unknown. Here, we examined the relative contributions of 13 neuropathologies to cognitive symptoms and dementia in RHI-exposed brain donors. METHODS: Neuropathologists examined brain tissue from 571 RHI-exposed donors and assessed for the presence of 13 neuropathologies, including CTE, Alzheimer disease (AD), Lewy body disease (LBD), and transactive response DNA-binding protein 43 (TDP-43) inclusions. Cognitive status was assessed by presence of dementia, Functional Activities Questionnaire, and Cognitive Difficulties Scale. Spearman rho was calculated to assess intercorrelation of pathologies. Additionally, frequencies of pathological co-occurrence were compared to a simulated distribution assuming no intercorrelation. Logistic and linear regressions tested associations between neuropathologies and dementia status and cognitive scale scores. RESULTS: The sample age range was 18-97 years (median = 65.0, interquartile range = 46.0-76.0). Of the donors, 77.2% had at least one moderate-severe neurodegenerative or cerebrovascular pathology. Stage III-IV CTE was the most common neurodegenerative disease (43.1%), followed by TDP-43 pathology, AD, and hippocampal sclerosis. Neuropathologies were intercorrelated, and there were fewer unique combinations than expected if pathologies were independent (p < 0.001). The greatest contributors to dementia were AD, neocortical LBD, hippocampal sclerosis, cerebral amyloid angiopathy, and CTE. INTERPRETATION: In this sample of RHI-exposed brain donors with wide-ranging ages, multiple neuropathologies were common and correlated. Mixed neuropathologies, including CTE, underlie cognitive impairment in contact sport athletes. ANN NEUROL 2024;95:314-324.

Financial Risk Aversion Among Older Black and White Adults.

OBJECTIVES: Risk aversion has a substantial impact on decision making and is associated with key demographic characteristics. However, few studies have investigated whether risk aversion varies by race. METHODS: We investigated racial differences in financial risk aversion in 684 older Black and White adults without dementia in the Minority Aging Research Study and Rush Memory and Aging Project matched for age, education, sex, and cognition using Mahalanobis distance. We also investigated whether select contextual factors (self-reported discrimination, socioeconomic status, and literacy) mediated or affective factors (trust, loneliness, and neuroticism) moderated any observed racial differences. RESULTS: In regression models adjusted for age, education, sex, and cognitive function, older Black adults were more risk averse than older White adults (Beta = 0.1264, standard error = 0.0227, p value ≤ .00001). None of the contextual or affective factors mediated or moderated this association. DISCUSSION: Older Black adults are more financially risk averse than older White adults. Because risk aversion may be associated with important financial and health outcomes in older age, more research is needed to investigate the reasons for this difference.

A Single-Nucleus Transcriptome-Wide Association Study Implicates Novel Genes in Depression Pathogenesis.

BACKGROUND: Depression, a common psychiatric illness and global public health problem, remains poorly understood across different life stages, which hampers the development of novel treatments. METHODS: To identify new candidate genes for therapeutic development, we performed differential gene expression analysis of single-nucleus RNA sequencing data from the dorsolateral prefrontal cortex of older adults (n = 424) in relation to antemortem depressive symptoms. Additionally, we integrated genome-wide association study results for depression (n = 500,199) along with genetic tools for inferring the expression of 14,048 unique genes in 7 cell types and 52 cell subtypes to perform a transcriptome-wide association study of depression followed by Mendelian randomization. RESULTS: Our single-nucleus transcriptome-wide association study analysis identified 68 candidate genes for depression and showed the greatest number being in excitatory and inhibitory neurons. Of the 68 genes, 53 were novel compared to previous studies. Notably, gene expression in different neuronal subtypes had varying effects on depression risk. Traits with high genetic correlations with depression, such as neuroticism, shared more transcriptome-wide association study genes than traits that were not highly correlated with depression. Complementing these analyses, differential gene expression analysis across 52 neocortical cell subtypes showed that genes such as KCNN2, SCAI, WASF3, and SOCS6 were associated with late-life depressive symptoms in specific cell subtypes. CONCLUSIONS: These 2 sets of analyses illustrate the utility of large single-nucleus RNA sequencing data both to uncover genes whose expression is altered in specific cell subtypes in the context of depressive symptoms and to enhance the interpretation of well-powered genome-wide association studies so that we can prioritize specific susceptibility genes for further analysis and therapeutic development.

A Microsimulation of Well-Being and Literacy Interventions to Reduce Scam Susceptibility in Older Adults.

Poor financial and health literacy and poor psychological well-being are significant correlates of scam susceptibility in older adults; yet, no research has examined whether interventions that target these factors may effectively reduce susceptibility. Using longitudinal data from older adults in the Rush Memory and Aging Project (MAP) (N = 1,231), we used microsimulations to estimate the causal effect of hypothetical well-being and literacy interventions on scam susceptibility over six years. Microsimulations can simulate a randomized trial to estimate intervention effects using observational data. We simulated hypotheticalinterventions that improved well-being or literacy scores by either 10% or 30% from baseline, or to the maximum scores, for an older adult population and for income and education subgroups. Simulations suggest thathypotheticalinterventions that increase well-being or literacy cause statistically significant reductions in scam susceptibility of older adults over time, but improving well-being caused a greater-albeit not significantly different-reduction compared to improving literacy.

Vulnerability of Older Adults to Government Impersonation Scams.

Importance: Financial fraud and scams targeting older adults are on the rise and pose serious public health and economic threats. Research on the vulnerability of older adults to fraud and scams relies almost exclusively on self-reported data, which have several intrinsic limitations. Thus, how older adults truly respond to fraud attempts remains unclear. Objective: To explore the vulnerability of older adults to a US government impersonation scam. Design, Setting, and Participants: This cross-sectional study, conducted from October to December 2021 among communities in the greater Chicago metropolitan area, was framed as a fictitious government agency reaching out to older adults about a potential compromise of personal information relevant to their Social Security and Medicare benefits. Participants were older adults participating in the Rush Memory and Aging Project, an ongoing cohort study of chronic conditions of aging. Data analysis was performed from February to August 2023. Exposures: Participants were exposed to deceptive materials through mailers, emails, and phone calls by a live agent. Main Outcomes and Measures: Based on the phone call data, participants were classified into 3 groups: no engagement (participants who did not answer the phone or call in), engagement (those who answered or called in but were skeptical about the legitimacy of the outreach and did not give away personal information), and conversion (participants who answered or called in without skepticism, or confirmed that they did not change their personal information, or provided the last 4 digits of their Social Security number). Results: A total of 644 older adults (501 [77.8%] female, 143 [22.2%] male), with a mean (SD) age of 85.6 (7.5) years, were included. A total of 441 (68.5%) participants did not engage, 97 (15.1%) engaged but raised skepticism, and 106 (16.4%) converted. Older adults who engaged but with skepticism had the highest cognition and financial literacy, while those in the conversion group had the lowest scam awareness. No differences were observed in psychological and other behavioral measures by the levels of engagement. Conclusions and Relevance: In this cross-sectional study using a behavioral experiment that mimicked a real-world imposter scam, a sizable number of older adults engaged without skepticism. Results suggest that many older adults, including those without cognitive impairment, are vulnerable to fraud and scams.

The Relationship of MRI-Derived Alzheimer's and Cerebrovascular-Related Signatures With Level of and Change in Health and Financial Literacy.

OBJECTIVE: The cortical thickness "signature" of Alzheimer's disease (AD-CT) and white matter hyperintensity (WMH) burden have each been associated with cognitive aging and incident AD and related dementias. Less is known about how these structural neuroimaging markers associate with other critical behaviors. We investigated associations of AD-CT and WMH volumes with a composite index of health and financial literacy given that the ability to access, understand, and utilize health and financial information significantly influences older adults' health outcomes. DESIGN, SETTING, PARTICIPANTS: Participants were 303 adults without dementia (age∼80 years; 74% women) from the Rush Memory and Aging Project. MEASUREMENTS: Baseline 3T MRI T1-weighted structural and T2-weighted FLAIR data were used to assess AD-CT and WMH volumes, respectively. Literacy was measured using questions designed to assess comprehension of health and financial information and concepts, yielding a total literacy score. Multivariable linear mixed effects regression models determined the relationship of each neuroimaging marker, first separately and then combined, with the level of and change in literacy. RESULTS: Reduced AD-CT and higher WMH at baseline were each associated with lower levels of literacy; only AD-CT was associated with the rate of decline in literacy over time. The association of AD-CT with change in literacy persisted when both neuroimaging markers were included in the same model. CONCLUSIONS: The cortical thickness signature of AD predicts changes in health and financial literacy in nondemented older adults suggesting that the multidimensional construct of health and financial literacy relies on specific brain networks implicated in AD.

Primacy and recency effects in verbal memory are differentially associated with post-mortem frontal cortex p-tau 217 and 202 levels in a mixed sample of community-dwelling older adults.

INTRODUCTION: Serial position effects in verbal memory are associated with in vivo fluid biomarkers and neuropathological outcomes in Alzheimer's disease (AD). To extend the biomarker literature, associations between serial position scores and postmortem levels of brain phosphorylated tau (p-tau) were examined, in the context of Braak stage of neurofibrillary tangle progression. METHOD: Participants were 1091 community-dwelling adults (Mage = 80.2, 68.9% female) from the Rush University Religious Orders Study and Memory and Aging Project who were non-demented at enrollment and followed for a mean of 9.2 years until death. The CERAD Word List Memory test administered at baseline and within 1 year of death was used to calculate serial position (primacy, recency) and total recall scores. Proteomic analyses quantified p-tau 217 and 202 from dorsolateral prefrontal cortex samples. Linear regressions assessed associations between cognitive scores and p-tau with Braak stage as a moderator. RESULTS: Cognitive status proximal to death indicated 34.7% were unimpaired, 26.2% met criteria for MCI, and 39.0% for dementia. Better baseline primacy recall, but not recency recall, was associated with lower p-tau 217 levels across Braak stages. Delayed recall showed a similar pattern as primacy. There was no main effect of immediate recall, but an interaction with Braak stages indicated a negative association with p-tau 217 level only in Braak V-VI. Within 1 year of death, there were no main effects for cognitive scores; however, recency, immediate and delayed recall scores interacted with Braak stage showing better recall was associated with lower p-tau 217 only in Braak V-VI. No associations were observed with p-tau 202. CONCLUSIONS: Primacy recall measured in non-demented adults may be sensitive to emergent tau phosphorylation that occurs in the earliest stages of AD. Serial position scores may complement the routinely used delayed recall score and p-tau biomarkers to detect preclinical AD.

A single-nucleus transcriptome-wide association study implicates novel genes in depression pathogenesis.

Background: Depression is a common psychiatric illness and global public health problem. However, our limited understanding of the biological basis of depression has hindered the development of novel treatments and interventions. Methods: To identify new candidate genes for therapeutic development, we examined single-nucleus RNA sequencing (snucRNAseq) data from the dorsolateral prefrontal cortex (N=424) in relation to ante-mortem depressive symptoms. To complement these direct analyses, we also used genome-wide association study (GWAS) results for depression (N=500,199) along with genetic tools for inferring the expression of 22,159 genes in 7 cell types and 55 cell subtypes to perform transcriptome-wide association studies (TWAS) of depression followed by Mendelian randomization (MR). Results: Our single-nucleus TWAS analysis identified 71 causal genes in depression that have a role in specific neocortical cell subtypes; 59 of 71 genes were novel compared to previous studies. Depression TWAS genes showed a cell type specific pattern, with the greatest enrichment being in both excitatory and inhibitory neurons as well as astrocytes. Gene expression in different neuron subtypes have different directions of effect on depression risk. Compared to lower genetically correlated traits (e.g. body mass index) with depression, higher correlated traits (e.g., neuroticism) have more common TWAS genes with depression. In parallel, we performed differential gene expression analysis in relation to depression in 55 cortical cell subtypes, and we found that genes such as ANKRD36, MADD, TAOK3, SCAI and CHUK are associated with depression in specific cell subtypes. Conclusions: These two sets of analyses illustrate the utility of large snucRNAseq data to uncover both genes whose expression is altered in specific cell subtypes in the context of depression and to enhance the interpretation of well-powered GWAS so that we can prioritize specific susceptibility genes for further analysis and therapeutic development.

Plasma p-tau181 and p-tau217 in discriminating PART, AD and other key neuropathologies in older adults.

We examined whether plasma p-tau181 and p-tau217 are specific biomarkers of pathologically confirmed Alzheimer's disease (AD). In particular, we investigated the utility of plasma p-tau for differentiating AD from primary age-related tauopathy (PART), as well as AD with mixed pathologies. Data came from 269 older adults who participated in the Religious Orders Study or the Rush Memory and Aging Project. Blood samples were collected during annual clinical evaluations. Participants died and underwent brain autopsy. P-tau181 and p-tau217 were quantified in the plasma samples proximate to death (average interval before death: 1.4 years) using Lilly-developed MSD immunoassays. Uniform neuropathologic evaluations assessed AD, PART, and other common degenerative and cerebrovascular conditions. Plasma p-tau217 was more strongly correlated with brain ß-amyloid and paired helical filament tau (PHFtau) tangles than p-tau181. Both p-tau markers were associated with greater odds of AD, but p-tau217 had higher accuracy (area under the ROC curve (AUC): 0.83) than p-tau181 (AUC: 0.76). Plasma p-tau markers were almost exclusively associated with AD pathologic indices with the exception of cerebral amyloid angiopathy. Compared to p-tau181, p-tau217 showed a higher AUC (0.82 versus 0.74) in differentiating AD from PART. For either p-tau, we did not observe a level difference between individuals with AD alone and those with mixed AD pathologies. In summary, plasma p-tau181and p-tau217 were specifically associated with AD pathological changes. Further, our data provide initial evidence that p-tau217 may be able to differentiate between AD and PART in individuals with comparable burdens of tau tangle pathology. These results demonstrate the specificity of p-tau217 for AD, supporting its use to identify patients suitable for anti-AD therapies including ß-amyloid immunotherapies.

Well-Being and Aging-Related Decline in Financial and Health Literacy in Advanced Age.

OBJECTIVES: Emerging evidence suggests that financial and health literacy deteriorates in advanced age. By contrast, well-being promotes health in aging. This study tested the hypothesis that well-being is associated with slower aging-related literacy decline. METHODS: Participants were 1,099 community-based older adults without dementia at baseline. Financial and health literacy was assessed at baseline and annually thereafter via a 32-item measure. Well-being was assessed at baseline via the 18-item version of Ryff's Scales of Psychological Well-Being. RESULTS: During up to 12 years of annual follow-up, literacy declined about 1 percentage point per year on average (ß = -0.91, standard error [SE] = 0.08, p < .001); however, there was considerable variation in change in literacy between participants (random slopes variance = 1.24, SE = 0.15, p < .001). In a linear mixed-effects model adjusted for age, sex, and education, higher well-being was associated with higher starting level of literacy (ß = 2.31, SE = 0.67, p = .001) and, critically, slower literacy decline (ß = 0.29, SE = 0.11, p = .01). The association of higher well-being with slower literacy decline persisted in models that additionally adjusted for income, medical conditions, depressive symptoms, and a robust measure of global cognition. DISCUSSION: This study suggests that well-being helps stave off aging-related literacy decline.

Change in Decision-Making Analysis and Preferences in Old Age.

OBJECTIVES: 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.

Predicting age at Alzheimer's dementia onset with the cognitive clock.

INTRODUCTION: Intervention of Alzheimer's dementia hinges on early diagnosis and advanced planning. This work utilizes the cognitive clock, a novel indicator of brain health, to develop a dementia prediction model that can be easily applied in broad settings. METHODS: Data came from over 3000 community-dwelling older adults. Cognitive age was estimated by aligning Mini-Mental State Examination (MMSE) scores to a clock that represents the typical cognitive aging profile. We identified a mean cognitive age at Alzheimer's dementia onset and predicted the corresponding chronological age at person-specific level. RESULTS: The mean chronological age at baseline was 78 years. A total of 881 (28%) participants developed Alzheimer's dementia. The mean cognitive age at onset was 91 years. The predicted chronological age at onset had a mean (standard deviation) of 87.6 (6.7) years. The model's prediction accuracy was supported by multiple testing statistics. DISCUSSION: Our model offers an easy-to-use tool for predicting person-specific age at Alzheimer's dementia onset.

Psychological Well-being Relates to Healthcare and Financial Decision Making in a Study of Predominantly White Older Adults.

The purpose of this study was to test the hypotheses that psychological well-being is associated with healthcare and financial decision making in older adults and that this association varies by the level of cognitive function. Participants were 1082 older adults (97% non-Latino White; 76% women; mean age = 81.04 years; SD = 7.53) without dementia (median MMSE score = 29.00, IQR = 27.86-30.00). In a regression model adjusted for age, gender, and years of education, higher levels of psychological well-being were associated with better decision making (estimate = 0.39, standard error [SE] = 0.11, p < .001), as was better cognitive function (estimate = 2.37, SE = 0.14, p < .0001). In an additional model, an interaction of psychological well-being and cognitive function was significant (estimate = -0.68, SE = 0.20, p < .001), such that higher levels of psychological well-being were most beneficial for decision making among participants with lower levels of cognitive function. Higher levels of psychological well-being may help sustain decision making among older persons, particularly those with lower levels of cognitive function.