Now or Later? Examining Social and Financial Decision Making in Middle-to-Older Aged Adults.

OBJECTIVES: Contextually driven decision making is multidimensional, as individuals need to contend with prioritizing both competing and complementary demands. However, data is limited as to whether temporal discounting rates vary as a function of framing (gains vs loss) and domain (monetary vs social) in middle-to-older aged adults. It is also unclear whether socioaffective characteristics like social isolation and loneliness are associated with temporal discounting. METHODS: Temporal discounting rates were examined across monetary gain, monetary loss, social gain, and social loss conditions in 140 adults aged 50-90 during the Omicron stage of the pandemic. Self-report measures assessed loneliness and social isolation levels. RESULTS: Results found evidence of steeper temporal discounting rates for gains as compared to losses in both domains. Social outcomes were also more steeply discounted than monetary outcomes, without evidence of an interaction with the framing condition. Socioeconomic and socioaffective factors were unexpectedly not associated with temporal discounting rates. DISCUSSION: Community-dwelling middle-to-older aged adults showed a preference for immediate rewards and devalued social outcomes more than monetary outcomes. These findings have implications for tailoring social and financial incentive programs for middle to later adulthood.

Neuropsychological and Neuroanatomical Features of Patients with Behavioral/Dysexecutive Variant Alzheimer's Disease (AD): A Comparison to Behavioral Variant Frontotemporal Dementia and Amnestic AD Groups.

BACKGROUND: An understudied variant of Alzheimer's disease (AD), the behavioral/dysexecutive variant of AD (bvAD), is associated with progressive personality, behavior, and/or executive dysfunction and frontal atrophy. OBJECTIVE: This study characterizes the neuropsychological and neuroanatomical features associated with bvAD by comparing it to behavioral variant frontotemporal dementia (bvFTD), amnestic AD (aAD), and subjects with normal cognition. METHODS: Subjects included 16 bvAD, 67 bvFTD, 18 aAD patients, and 26 healthy controls. Neuropsychological assessment and MRI data were compared between these groups. RESULTS: Compared to bvFTD, bvAD showed more significant visuospatial impairments (Rey Figure copy and recall), more irritability (Neuropsychological Inventory), and equivalent verbal memory (Philadelphia Verbal Learning Test). Compared to aAD, bvAD indicated more executive dysfunction (F-letter fluency) and better visuospatial performance. Neuroimaging analysis found that bvAD showed cortical thinning relative to bvFTD posteriorly in left temporal-occipital regions; bvFTD had cortical thinning relative to bvAD in left inferior frontal cortex. bvAD had cortical thinning relative to aAD in prefrontal and anterior temporal regions. All patient groups had lower volumes than controls in both anterior and posterior hippocampus. However, bvAD patients had higher average volume than aAD patients in posterior hippocampus and higher volume than bvFTD patients in anterior hippocampus after adjustment for age and intracranial volume. CONCLUSION: Findings demonstrated that underlying pathology mediates disease presentation in bvAD and bvFTD.

Specific Sleep Health Domains as Predictors of Executive Function in Older Adults.

OBJECTIVES: Sleep health and executive function are multifaceted constructs that decline with age. Some evidence suggests that poor sleep health may underlie declines in executive function, but this relationship is not consistently found in cognitively normal older adults. The authors systematically investigated distinct sleep health domain associations with specific aspects of executive function. METHODS: Community-dwelling older adults completed clinical interviews, comprehensive neuropsychological assessments, and subjective sleep measures. Four sleep health domains were investigated: satisfaction/quality, sleep efficiency, sleep duration, and daytime sleepiness/fatigue. Hierarchical multiple regression analyses, adjusting for significant covariates, examined whether the sleep health domains differentially predicted executive function. RESULTS: Separate analyses found that greater sleep efficiency was associated with better response inhibition, while greater daytime sleepiness/fatigue was associated with worse cognitive flexibility. Categorical differences in sleep duration indicated that average durations, compared with short and long durations, had better executive function performance across measures. Sleep satisfaction/quality was not statistically associated with executive function. CONCLUSIONS: These findings have implications for sleep assessment and its intervention. Routine screening of sleep duration, efficiency, and daytime fatigue may be particularly useful in identifying those at greater risk of executive dysfunction. Targeting specific problems in sleep may serve to improve cognitive control and efficiency in older adults. Future research is warranted to establish the optimal hours of sleep duration for cognitive health.

Slower gait speed increases risk of falling in older adults with depression and cognitive complaints.

Slowed gait is one of the strongest predictors of fall risk in older adults. The present study investigated whether gait speed mediated the relationship between depression and fall history in 147 older adults presenting to a memory clinic for cognitive complaints. Depression, cognitive status, gait speed, and number of falls within the last year were the primary measures. Results revealed fallers, relative to non-fallers, had slower gait speed and higher depression scores. As hypothesized, analyses using the PROCESS macro found that gait mediated the relationship between depression and fall history. Additionally, the combination of depression and mild cognitive impairments (MCI) associated with a significantly greater likelihood of falling. Our findings indicate that combined depression and MCI have additive effects on fall risk, likely through the destabilizing effect of slowed gait on balance. Better understanding the underlying pathophysiology involved in MCI and depression-related gait disturbances may lead to improved intervention targets for fall risk prevention.

Trait mindfulness associations with executive function and well-being in older adults.

OBJECTIVES: The current study investigated trait mindfulness associations with distinct aspects of executive function. We also aimed to characterize relationships between trait mindfulness with measures of psychological risk and resilience within adults aged 55-87 years. METHOD: In this cross-sectional study, 121 adults completed neuropsychological measures of working memory, mental set-shifting, and inhibition, as well as a battery of well-validated psychological self-report measures. The Mindful Attention Awareness Scale (MAAS) measured trait mindfulness. RESULTS: Trait mindfulness was associated with greater age, years of education and self-efficacy, and less perceived stress, depression, anxiety, and subjective cognitive concerns. Hierarchal multiple regression analyses showed that trait mindfulness was a significant predictor of inhibitory control, even after adjusting for age, education, and global cognition in the model. Trait mindfulness was not significantly associated with working memory or mental set-shifting. Follow-up analyses using the PROCESS macro revealed that trait mindfulness mediated the relationship between perceived stress and inhibitory control. CONCLUSION: Trait mindfulness was associated with measures of greater well-being and mental health. Our results also indicate that trait mindfulness may provide psychological resilience by attenuating perceived stress and enhancing the capacity to intentionally suppress irrelevant information and automatic responses.

Are Adverse Childhood Experiences Associated with Worse Cognitive Function in Older Adults?

OBJECTIVES: Adverse childhood experiences (ACE) are associated with an increased risk for dementia, but this relationship and modifying factors are poorly understood. This study is the first to our knowledge to comprehensively examine the effect of ACE on specific cognitive functions and measures associated with greater risk and resiliency to cognitive decline in independent community-dwelling older adults. METHODS: Verbal/nonverbal intelligence, verbal memory, visual memory, and executive attention were assessed. Self-report measures examined depression, self-efficacy, and subjective cognitive concerns (SCC). The ACE questionnaire measured childhood experiences of abuse, neglect, and household dysfunction. RESULTS: Over 56% of older adults reported an adverse childhood event. ACE scores were negatively associated with income and years of education and positively associated with depressive symptoms and SCC. ACE scores were a significant predictor of intellectual function and executive attention; however, these relationships were no longer significant after adjusting for education. Follow-up analyses using the PROCESS macro revealed that relationships among higher ACE scores with intellectual function and executive attention were mediated by education. CONCLUSIONS: Greater childhood adversity may increase vulnerability for cognitive impairment by impacting early education, socioeconomic status, and mental health. These findings have clinical implications for enhancing levels of cognitive reserve and addressing modifiable risk factors to prevent or attenuate cognitive decline in older adults.

Predictors of Heterogeneity in Cognitive Function: APOE-e4, Sex, Education, Depression, and Vascular Risk.

OBJECTIVE: Mild cognitive impairment and dementia are clinically heterogeneous disorders influenced by diverse risk factors. Improved characterization of the effect of multiple risk factors influence on specific cognitive functions may improve understanding of mechanisms in early cognitive change and lead to more effective interventions. METHODS: Structural equation modeling (SEM) simultaneously examined the effects of modifiable (education, depression, and metabolic/vascular risk) and nonmodifiable risk factors (age, sex, and apolipoprotein E-ɛ4 allele [APOE-e4] status) on specific cognitive domains in 461 cognitively normal older adults. RESULTS: The hypothesized model(s) provided an adequate fit for the data. Sex differences in cognition, depression, and vascular risk were found. On average, men were higher in vascular risk with generally lower cognitive performance than women; women were more likely to have depression. APOE-e4 associated with depression but not age, sex, or metabolic/vascular risk. Depression associated with lower executive attention, memory, and language performance, whereas metabolic/vascular risk associated with lower executive attention, memory, and working memory. Older age and lower education are associated with worse performance across the cognitive domains. The combined risk factors accounted for 16%-47% of the variance in the cognitive domains. CONCLUSIONS: Results highlight the combined effect of risk factors on cognitive function. Future research is needed to determine whether the multifactorial risk effects on cognition vary by sex. Precision medicine approaches that integrate neuropsychological services may improve diagnostic accuracy and earlier identification of those at risk of cognitive decline.

Clinical Correlates of Alzheimer's Disease Cerebrospinal Fluid Analytes in Primary Progressive Aphasia.

Background: While primary progressive aphasia (PPA) is associated with frontotemporal lobar degeneration (FTLD) pathology due to tau or TDP, clinical-pathological studies also demonstrate many cases have Alzheimer's disease (AD) pathology. The logopenic variant of PPA (lvPPA) is most often associated with AD pathology, but this has proven to be the least reliable PPA to diagnose using published clinical criteria. In this study, we used cerebrospinal fluid (CSF) analytes to identify patients with likely AD pathology, and relate phenotypic features of lvPPA to CSF. Methods: We studied 46 PPA patients who had available CSF analytes, including 26 with a clinical diagnosis of lvPPA, 9 with non-fluent/agrammatic variant (naPPA), and 11 with semantic variant (svPPA). We identified patients with likely AD pathology using amyloid-beta 1-42 (Aß1-42) < 192 pg/ml and assessed MRI gray matter atrophy in these patients. Results: We found that 23 (49%) of 46 PPA patients have a low CSF Aß1-42 level consistent with AD pathology. Twenty-one (91%) of 23 patients had a lvPPA phenotype, and 18 (79%) of 23 cases with an elevated CSF Aß1-42 level did not have a lvPPA phenotype. Patients with a lvPPA phenotype demonstrated GM atrophy in the left lateral temporal lobe, and this was also seen in those with a CSF Aß1-42 level < 192 pg/ml. Conclusion: The lvPPA clinical phenotype may be a useful screen for CSF analytes that are a surrogate for likely AD pathology, and may help establish eligibility of these patients for disease-modifying treatment trials.

Occupational attainment influences longitudinal decline in behavioral variant frontotemporal degeneration.

To evaluate whether occupational attainment influences the trajectory of longitudinal cognitive decline in behavioral variant frontotemporal degeneration (bvFTD). Single-center, retrospective, longitudinal study. Sixty-three patients meeting consensus criteria for bvFTD underwent evaluation at the University of Pennsylvania Frontotemporal Degeneration Center. All patients were studied longitudinally on letter-guided fluency, category-naming fluency and Boston Naming Test (BNT). Occupational attainment was defined categorically by assigning each individual's occupation to a professional or non-professional category. Linear mixed-effects models evaluated the interaction of neuropsychological performance change with occupational status. Regression analyses were used to relate longitudinal decline in executive function to baseline MRI grey matter atrophy. Higher occupational status was associated with a more severe slope of cognitive decline on letter-guided fluency and category-naming fluency, but not BNT. Faster rates of longitudinal decline on letter-guided and category-naming fluency were associated with more severe baseline grey matter atrophy in right dorsolateral and inferior frontal regions. Our longitudinal findings suggest that bvFTD individuals with higher lifetime cognitive experience demonstrate more rapid decline on measures of executive function. This finding converges with cross-sectional evidence suggesting that lifetime cognitive experiences contribute to heterogeneity in clinical progression in bvFTD.

Longitudinal decline in speech production in Parkinson's disease spectrum disorders.

We examined narrative speech production longitudinally in non-demented (n=15) and mildly demented (n=8) patients with Parkinson's disease spectrum disorder (PDSD), and we related increasing impairment to structural brain changes in specific language and motor regions. Patients provided semi-structured speech samples, describing a standardized picture at two time points (mean±SD interval=38±24months). The recorded speech samples were analyzed for fluency, grammar, and informativeness. PDSD patients with dementia exhibited significant decline in their speech, unrelated to changes in overall cognitive or motor functioning. Regression analysis in a subset of patients with MRI scans (n=11) revealed that impaired language performance at Time 2 was associated with reduced gray matter (GM) volume at Time 1 in regions of interest important for language functioning but not with reduced GM volume in motor brain areas. These results dissociate language and motor systems and highlight the importance of non-motor brain regions for declining language in PDSD.

Narrative Organization Deficit in Lewy Body Disorders Is Related to Alzheimer Pathology.

Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort (n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia (n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE (p < 0.001). We used a previously reported procedure that probes patients' judgments of the organization of brief, familiar narratives (e.g., going fishing, wrapping a present). A subgroup of 24 patients had MRI assessment of regional gray matter (GM) atrophy and cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer's disease (AD) pathology, including beta amyloid (Aß), total-tau (t-tau), and phosphorylated-tau (p-tau). Results: Mildly demented LBD patients had a significant deficit judging narratives compared to non-demented patients, but this deficit was not correlated with MMSE. Regression analyses instead related narrative organization to regions of frontal GM atrophy, and CSF levels of Aß and t-tau associated with presumed AD pathology in these frontal regions. Conclusion: These findings are consistent with the hypothesis that CSF markers of AD pathology associated with frontal regions play a role in difficulty organizing narratives in LBD.

Topography of dilated perivascular spaces in subjects from a memory clinic cohort.

OBJECTIVE: To investigate whether the topography of dilated perivascular spaces (DPVS) corresponds with markers of particular small-vessel diseases such as cerebral amyloid angiopathy and hypertensive vasculopathy. METHODS: Patients were recruited from an ongoing single-center prospective longitudinal cohort study of patients evaluated in a memory clinic. All patients underwent structural, high-resolution MRI, and had a clinical assessment performed within 1 year of scan. DPVS were rated in basal ganglia (BG-DPVS) and white matter (WM-DPVS) on T1 sequences, using an established 4-point semiquantitative score. DPVS degree was classified as high (score > 2) or low (score ≤ 2). Independent risk factors for high degree of BG-DPVS and WM-DPVS were investigated. RESULTS: Eighty-nine patients were included (mean age 72.7 ± 9.9 years, 57% female). High degree of WM-DPVS was more frequent than low degree in patients with presence of strictly lobar microbleeds (45.5% vs 28.4% of subjects). High BG-DPVS degree was associated with older age, hypertension, and higher white matter hyperintensity volumes. In multivariate analysis, increased lobar microbleed count was an independent predictor of high degree of WM-DPVS (odds ratio [OR] 1.53 [95% confidence interval (CI) 1.06-2.21], p = 0.02). By contrast, hypertension was an independent predictor of high degree of BG-DPVS (OR 9.4 [95% CI 1-85.2], p = 0.04). CONCLUSIONS: The associations of WM-DPVS with lobar microbleeds and BG-DPVS with hypertension raise the possibility that the distribution of DPVS may indicate the presence of underlying small-vessel diseases such as cerebral amyloid angiopathy and hypertensive vasculopathy in patients with cognitive impairment.

Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy.

OBJECTIVE: In addition to its role in hemorrhagic stroke, advanced cerebral amyloid angiopathy (CAA) is also associated with ischemic lesions and vascular cognitive impairment. We used functional magnetic resonance imaging (MRI) techniques to identify CAA-associated vascular dysfunction. METHODS: Functional MRI was performed on 25 nondemented subjects with probable CAA (mean ± standard deviation age, 70.2 ± 7.8 years) and 12 healthy elderly controls (age, 75.3 ± 6.2 years). Parameters measured were reactivity to visual stimulation (quantified as blood oxygen level-dependent [BOLD] response amplitude, time to peak response, and time to return to baseline after stimulus cessation) and resting absolute cerebral blood flow in the visually activated region (measured by arterial spin labeling). RESULTS: CAA subjects demonstrated reduced response amplitude (percentage change in BOLD signal, 0.65 ± 0.28 vs 0.89 ± 0.14; p < 0.01), prolonged time to peak (11.1 ± 5.1 vs 6.4 ± 1.8 seconds; p < 0.001), and prolonged time to baseline (16.5 ± 6.7 vs 11.6 ± 3.1 seconds; p < 0.001) relative to controls. These differences were independent of age, sex, and hypertension in multivariable analysis and were also present in secondary analyses excluding nonresponsive voxels or voxels containing chronic blood products. Within the CAA group, longer time to peak correlated with overall volume of white matter T2 hyperintensity (Pearson correlation, 0.53; p = 0.007). Absolute resting blood flow in visual cortex, in contrast, was essentially identical between the groups (44.0 ± 12.6 vs 45.0 ± 10.0 ml/100 g/min, p = 0.8). INTERPRETATION: Functional MRI identifies robust differences in both amplitude and timing of the response to visual stimulation in advanced CAA. These findings point to potentially powerful approaches for identifying the mechanistic links between vascular amyloid deposits, vascular dysfunction, and CAA-related brain injury.

Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy.

OBJECTIVE: We aimed to determine whether amyloid imaging can help predict the location and number of future hemorrhages in cerebral amyloid angiopathy (CAA). METHODS: We performed a longitudinal cohort study of 11 patients with CAA without dementia who underwent serial brain MRIs after baseline amyloid imaging with Pittsburgh compound B (PiB). Mean distribution volume ratio (DVR) of PiB was determined at the sites of new micro/macrobleeds identified on follow-up MRI and compared with PiB retention at "simulated" hemorrhages, randomly placed in the same subjects using a probability distribution map of CAA-hemorrhage location. Mean PiB retention at the sites of observed new bleeds was also compared to that in shells concentrically surrounding the bleeds. Finally the association between number of incident bleeds and 3 regional amyloid measures were obtained. RESULTS: Nine of 11 subjects had at least one new microbleed on follow-up MRI (median 4, interquartile range [IQR] 1-9) and 2 had 5 new intracerebral hemorrhages. Mean DVR was greater at the sites of incident bleeds (1.34, 95% confidence interval [CI] 1.23-1.46) than simulated lesions (1.14, 95% CI 1.07-1.22, p < 0.0001) in multivariable models. PiB retention decreased with increasing distance from sites of observed bleeds (p < 0.0001). Mean DVR in a superior frontal/parasagittal region of interest correlated independently with number of future hemorrhages after adjustment for relevant covariates (p = 0.003). CONCLUSIONS: Our results provide direct evidence that new CAA-related hemorrhages occur preferentially at sites of increased amyloid deposition and suggest that PiB-PET imaging may be a useful tool in prediction of incident hemorrhages in patients with CAA.

A comparison of acute hemorrhagic stroke outcomes in 2 populations: the Crete-Boston study.

BACKGROUND AND PURPOSE: Although corticosteroid use in acute hemorrhagic stroke is not widely adopted, management with intravenous dexamethasone has been standard of care at the University Hospital of Heraklion, Crete with observed outcomes superior to those reported in the literature. To explore this further, we conducted a retrospective, multivariable-adjusted 2-center study. METHODS: We studied 391 acute hemorrhagic stroke cases admitted to the University Hospital of Heraklion, Crete between January 1997 and July 2010 and compared them with 510 acute hemorrhagic stroke cases admitted to Massachusetts General Hospital, Boston, from January 2003 to September 2009. Of the Cretan cases, 340 received a tapering scheme of intravenous dexamethasone, starting with 16 to 32 mg/day, whereas the Boston patients were managed without steroids. RESULTS: The 2 cohorts had comparable demographics and stroke severity on admission, although anticoagulation was more frequent in Boston. The in-hospital mortality was significantly lower on Crete (23.8%, n=340) than in Boston (38.0%, n=510; P<0.001) as was the 30-day mortality (Crete: 25.4%, n=307; Boston: 39.4%, n=510; P<0.001). Exclusion of patients on anticoagulants showed even greater differences (30-day mortality: Crete 20.8%; n=259; Boston 37.0%; n=359; P<0.001). The improved survival on Crete was observed 3 days after initiation of intravenous dexamethasone and was pronounced for deep-seated hemorrhages. After adjusting for acute hemorrhagic stroke volume/location, Glasgow Coma Scale, hypertension, diabetes mellitus, smoking, coronary artery disease and statin, antiplatelet, and anticoagulant use, intravenous dexamethasone treatment was associated with better functional outcomes and significantly lower risk of death at 30 days (OR, 0.357; 95% CI, 0.174-0.732). CONCLUSIONS: This study suggests that intravenous dexamethasone improves outcome in acute hemorrhagic stroke and supports a randomized clinical trial using this approach.

MRI markers of small vessel disease in lobar and deep hemispheric intracerebral hemorrhage.

BACKGROUND AND PURPOSE: MRI evidence of small vessel disease is common in intracerebral hemorrhage (ICH). We hypothesized that ICH caused by cerebral amyloid angiopathy (CAA) or hypertensive vasculopathy would have different distributions of MRI T2 white matter hyperintensity (WMH) and microbleeds. METHODS: Data were analyzed from 133 consecutive patients with primary supratentorial ICH and adequate MRI sequences. CAA was diagnosed using the Boston criteria. WMH segmentation was performed using a validated semiautomated method. WMH and microbleeds were compared according to site of symptomatic hematoma origin (lobar versus deep) or by pattern of hemorrhages, including both hematomas and microbleeds, on MRI gradient recalled echo sequence (grouped as lobar only-probable CAA, lobar only-possible CAA, deep hemispheric only, or mixed lobar and deep hemorrhages). RESULTS: Patients with lobar and deep hemispheric hematoma had similar median normalized WMH volumes (19.5 cm versus 19.9 cm(3), P=0.74) and prevalence of >or=1 microbleed (54% versus 52%, P=0.99). The supratentorial WMH distribution was similar according to hemorrhage location category; however, the prevalence of brain stem T2 hyperintensity was lower in lobar hematoma versus deep hematoma (54% versus 70%, P=0.004). Mixed ICH was common (23%). Patients with mixed ICH had large normalized WMH volumes and a posterior distribution of cortical hemorrhages similar to that seen in CAA. CONCLUSIONS: WMH distribution is largely similar between CAA-related and non-CAA-related ICH. Mixed lobar and deep hemorrhages are seen on MRI gradient recalled echo sequence in up to one fourth of patients; in these patients, both hypertension and CAA may be contributing to the burden of WMH.