Dementia: Common Syndromes and Modifiable Risk and Protective Factors.

Dementia is an umbrella term for multiple conditions that lead to progressive cognitive decline and impaired activities of daily living. Neuropsychological evaluation is essential for characterizing the distinct cognitive and behavioral profile that can aid in the diagnostic process and treatment planning for dementia. Modifiable risk factors for dementia such as nutrition, physical activity, sleep, cognitive and social engagement, and stress provide important avenues for prevention. Neurologists and other health care providers can help patients reduce their risk for dementia by providing them with education about modifiable factors and connecting them to resources to empower them to engage in brain-healthy behavior.

Neurodegenerative Plasma Biomarkers for Prediction of Hippocampal Atrophy in Older Adults with Suspected Alzheimer's Disease in Kinshasa, Democratic Republic of Congo.

Objective: The hippocampus is one of the first brain structures affected by Alzheimer's disease (AD), and its atrophy is a strong indicator of the disease. This study investigates the ability of plasma biomarkers of AD and AD-related dementias-amyloid-ß (Aß42/40), phosphorylated tau-181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)-to predict hippocampal atrophy in adult individuals in Kinshasa, Democratic Republic of Congo (DRC). Methods: Eighty-five adult individuals (40 healthy and 45 suspected AD) over 65 years old were evaluated using the Community Screening Instrument for Dementia and Alzheimer's Questionnaire (AQ). Core AD biomarkers (Aß42/40 and p-tau181) and non-specific neurodegeneration biomarkers (NfL, GFAP) were measured in blood samples collected at the study visit. Hippocampal volumes were measured using magnetic resonance imaging (MRI). General linear regression was used to evaluate differences in biomarker concentrations by neurological status. Logistic regression models were used to create receiver operating characteristic curves and calculate areas under the curve (AUCs) with and without clinical covariates to determine the ability of biomarker concentrations to predict hippocampal atrophy. Plasma biomarkers were used either individually or in combination in the models. Results: Elevated p-tau181 was associated with left hippocampal (LH) atrophy p= 0.020). Only higher p-tau181 concentrations were significantly associated with 4.2-fold increased odds [OR=4.2 (1.5-18.4)] of hippocampal atrophy per standard deviation. The AUC of plasma biomarkers without clinical covariates to discriminate LH, RH, and total hippocampal (TH) or both hippocampi atrophy ranged between 90% to 94%, 76% to 82%, and 85% to 87%, respectively. The AUC of models including clinical covariates and AD biomarkers used in combination to discriminate LH, RH, and TH ranged between 94%-96%, 81%-84%, and 88%-90%, respectively. Conclusion: These results indicate that, consistent with studies in other settings, core AD plasma biomarkers can predict hippocampal atrophy in a population in Sub-Saharan Africa.

Preliminary reference values for Alzheimer's disease plasma biomarkers in Congolese individuals with and without Alzheimer's disease.

Background: Western countries have provided reference values (RV) for Alzheimer's disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations. Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid- ß (Aß42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor α (TNFα) in Congolese adults with and without dementia. Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers Aß42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFα analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youden's index. Results: In this sample of 85 adults, 40 (47%) had dementia, 38 (45.0%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary cutoffs of various plasma in pg/ml were 0.061 for Aß42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.74 (0.61, 0.86)] followed by GFAP [0.72 (0.61, 0.83), and Nfl [0.71 (0.60, 0.82)] had the highest AUC compared to other plasma biomarkers. Conclusions: This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, classification, and prognosis of AD in Congolese adults.

Physical activity moderates the association between executive function and functional connectivity in older adults.

Recent evidence suggests that physical activity may influence the functional connectivity of the aging brain. The purpose of this study was to examine the influence of physical activity on the association between executive function and functional connectivity of key brain networks and graph theory metrics in community-dwelling older adults. Participants were 47 older adults (M = 73 years; SD = 5.92) who participated in neuropsychological testing, physical activity measurements, and magnetic resonance imaging (MRI). Seed-to-voxel moderation analyses and graph theory analyses were conducted. Physical activity was significantly positively associated with default mode network functional connectivity (DMN FC; Posterior Cingulate Gyrus, p-FDR = 0.005; Frontal Pole (L), p-FDR = 0.005; Posterior Cingulate Gyrus, p-FDR = 0.006; Superior Frontal Gyrus (L), p-FDR = 0.016) and dorsal attention network functional connectivity (DAN FC; Inferior Frontal Gyrus Pars Opercularis (R), p-FDR = 0.044). The interaction between physical activity and executive function on the DMN FC and DAN FC was analyzed. The interaction between executive function and physical activity was significantly associated with DMN FC. When this significant interaction was probed, the association between physical activity and DMN FC differed between levels of high and low executive function such that the association was only significant at levels of high executive function. These results suggest that greater physical activity in later life is associated with greater DMN and DAN FC and provides evidence for the importance of physical activity in cognitively healthy older adults.

Pre-Morbid IQ Moderates the Relationship between Cognitive Performance and Performance-Based Functional Status in Older Adults.

Objectives: The current study sought to evaluate the relationship between cognitive performance and Instrumental Activities of Daily Living (IADL) performance in a population of community dwelling older adults, and assess to what extent this relationship is moderated by cognitive reserve (Premorbid-IQ)Methods: 123 community-dwelling older adults completed a general cognitive assessment, a word-reading based premorbid-IQ estimate (PMIQE) measure, and the performance-based Direct Assessment of Functional Status, Revised (DAFS-R). Moderated regression analysis was used to assess the influence of PMIQE on the relationship between cognitive performance and IADLs.Results: There was a significant main effect of cognitive performance on IADLs, and no main effect of PMIQE on functional IADLs. There was a significant moderating effect of PMIQE on the relationship between cognitive performance and IADLs performance, such that at higher levels of PMIQE, cognitive performance scores became slightly less predictive of weaknesses in IADLs.Conclusions: Results suggest that for individuals with high reserve, assessment of cognitive performance alone may not be robust a predictor of IADLs functioning.Clinical implications: In estimating functional abilities as a consequence of cognitive performance, consideration should be given to premorbid-IQ/cognitive reserve.

The Relations Between Physical Activity Level, Executive Function, and White Matter Microstructure in Older Adults.

The population of older adults is increasing, indicating a need to examine factors that may prevent or mitigate age-related cognitive decline. The current study examined whether microstructural white matter characteristics mediated the relation between physical activity and executive function in older adults without any self-reported psychiatric and neurological disorders or cognitive impairment (N = 43, mean age = 73 y). Physical activity was measured by average intensity and number of steps via accelerometry. Diffusion tensor imaging was used to examine microstructural white matter characteristics, and neuropsychological testing was used to examine executive functioning. Parallel mediation models were analyzed using microstructural white matter regions of interest as mediators of the association between physical activity and executive function. Results indicated that average steps was significantly related to executive function (ß = 0.0003, t = 2.829, P = .007), while moderate to vigorous physical activity was not (ß = 0.0007, t = 1.772, P = .08). White matter metrics did not mediate any associations. This suggests that microstructural white matter characteristics alone may not be the mechanism by which physical activity impacts executive function in aging.

A Multi-method Investigation of the Personality Correlates of Functional Ability in Older Adults.

OBJECTIVES: This study evaluated the role of personality in predicting functional ability (FA) in older adults using self-report, collateral report, and performance-based measures of FA. METHODS: Participants included older adults (N = 131) who completed a personality measure (NEO-FFI), a self-report of FA (OARS ADL), and participated in a performance-based assessment of FA (DAFS-R). In addition, each participant had a collateral complete a collateral report of FA (OARS ADL). Bivariate correlations were computed to assess how Five Factor Model traits were related to self-report, collateral, and performance-based measures of FA. RESULTS: Neuroticism was negatively related to self-reported FA (r = - .27) and collateral-reported FA (r = - .18) and Conscientiousness was positively related to self-reported FA (r = .25). None of the traits were significantly related to the performance-based measure of FA. CONCLUSIONS: These results suggest that personality traits can impact self-reported FA in older adults and underscore the importance of assessing FA in older adults using multiple methods, particularly performance-based measures. CLINICAL IMPLICATIONS: Clinicians should consider how personality may impact FA in older adults and multiple methods of FA performance should be examined to better tailor recommendations.

Education Differentially Buffers Cognitive Performance in Black and White Older Adults.

OBJECTIVES: Given that black American older adults are more likely to have lower educational attainment and perform worse on cognitive tests than white Americans, we examined whether increased education would confer greater cognitive advantage to black Americans on measures of global and specific domains of cognitive function. METHODS: The sample included 522 community-dwelling older adults from a larger study. An analysis of covariance was conducted with race and education as between-participant factors and global cognition as the dependent variable. A multivariate analysis of covariance was conducted with five cognitive domains (immediate memory, visuospatial/constructional ability, language, attention, and delayed memory) as the dependent variables. RESULTS: Significant main effects indicated that black Americans, F(1,516) = 29.18, p < .001, and individuals with less education, F(1,516) = 44.93, p < .001, evidenced lower cognitive functioning, controlling for age and overall health status, and the interaction term reached statistical significance, F(1,516) = 7.95, p = .005. The impact of education on global cognitive function for black participants was more than twice as large (Cohen's d = 1.30) than for white participants (Cohen's d = .52). There was a significant race × education interaction for the cognitive domain of attention (p < .001) and a composite measure of non-memory domains (i.e., language, visuospatial/constructional, and attention; p < .001). DISCUSSION: Our findings suggest that educational attainment is particularly important for black Americans with respect to global cognitive function, attention, and non-memory domains.

Body mass index and its relation to neuropsychological functioning and brain volume in healthy older adults.

Obesity is a growing concern worldwide because of its adverse health effects, including its negative impact on cognitive functioning. This concern is especially relevant for older adults, who are already likely to experience some cognitive decline and loss of brain volume due to aging, (Gea et al., 2002). However, there is some evidence that higher body mass index (BMI) may actually be protective in later life (Hughes et al., 2009; Luchsinger et al., 2007; Nilsson and Nilsson, 2009; Sturman et al., 2008). Therefore, the purpose of the current study was to assess the relationship between BMI and neuropsychological functioning in older adults, and concurrently the relationship between BMI and brain volume. Older adults (N = 88) reported height and weight to determine BMI (M = 26.5) based on Centers for Disease Control and Prevention (CDC) guidelines. Cognitive function was assessed with the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Brain volume measurements were evaluated via structural MRI. Results indicated no association between BMI and neuropsychological functioning. There was a significant association between BMI and total grey matter volume while controlling for age and years of education (ß = 0.208, p = .026, ΔR2 = 0.043), indicating that as BMI increased, brain volume in these areas modestly increased. However, these results did not survive multiple comparison corrections and were further attenuated to near significance when sex was explicitly added as an additional covariate. Nevertheless, while replication is clearly needed, these results suggest that moderately greater BMI in later life may modestly attenuate concomitant grey matter volume decline.

Lutein and Zeaxanthin Are Positively Associated with Visual-Spatial Functioning in Older Adults: An fMRI Study.

Lutein (L) and zeaxanthin (Z) are two xanthophyll carotenoids that have antioxidant and anti-inflammatory properties. Previous work has demonstrated their importance for eye health and preventing diseases such as age-related macular degeneration. An emerging literature base has also demonstrated the importance of L and Z in cognition, neural structure, and neural efficiency. The present study aimed to better understand the mechanisms by which L and Z relate to cognition, in particular, visual-spatial processing and decision-making in older adults. We hypothesized that markers of higher levels of L and Z would be associated with better neural efficiency during a visual-spatial processing task. L and Z were assessed via standard measurement of blood serum and retinal concentrations. Visual-spatial processing and decision-making were assessed via a judgment of line orientation task (JLO) completed during a functional magnetic resonance imaging (fMRI) scan. The results demonstrated that individuals with higher concentrations of L and Z showed a decreased blood-oxygen-level dependent (BOLD) signal during task performance (i.e., "neural efficiency") in key areas associated with visual-spatial perception, processing, decision-making, and motor coordination, including the lateral occipital cortex, occipital pole, superior and middle temporal gyri, superior parietal lobule, superior and middle frontal gyri, and pre- and post-central gyri. To our knowledge, this is the first investigation of the relationship of L and Z to visual-spatial processing at a neural level using in vivo methodology. Our findings suggest that L and Z may impact brain health and cognition in older adults by enhancing neurobiological efficiency in a variety of regions that support visual perception and decision-making.

Brain activation changes during locomotion in middle-aged to older adults with multiple sclerosis.

Mobility and cognitive impairments are common in persons with multiple sclerosis (MS), and are expected to worsen with increasing age. However, no studies, to date, in part due to limitations of conventional neuroimaging methods, have examined changes in brain activation patterns during active locomotion in older patients with MS. This study used functional Near Infrared Spectroscopy (fNIRS) to evaluate real-time neural activation differences in the pre-frontal cortex (PFC) between middle-aged to older adults with MS and healthy controls during single (Normal Walk; NW) and dual-task (Walking While Talking; WWT) locomotion tasks. Eight middle-aged to older adults with MS and eight healthy controls underwent fNIRS recording while performing the NW and WWT tasks with an fNIRS cap consisting of 16 optodes positioned over the forehead. The MS group had greater elevations in PFC oxygenation levels during WWT compared to NW than healthy controls. There was no walking performance difference between groups during locomotion. These findings suggest that middle-aged to older individuals with MS might be able to achieve similar levels of performance through the use of increased brain activation. This study is the first to investigate brain activation changes during the performance of simple and divided-attention locomotion tasks in MS using fNIRS.