Apathy as a determinant of health behaviors in older adults: Implications for dementia risk reduction

INTRODUCTION: Long-term improvements in physical inactivity and other behavioral risk factors are integral to dementia risk reduction; however, sustained behavior change is challenging. Apathy, depression, and fatigue may impact engagement in health behaviors, but their presentation overlaps. This study investigates whether these symptoms are differentially associated with multiple health behaviors. METHODS: In 1037 community-dwelling older adults without dementia (aged 70–90, 55% women), regression analyses examined apathy, depression, and fatigue as predictors of health behaviors (physical activity, diet, alcohol, smoking) and a behavioral risk index. RESULTS: Apathy was associated with reduced physical activity and alcohol use, and one or multiple behavioral risk factors. No or inconsistent relations were found between depression or fatigue and health behaviors. DISCUSSION: Apathy is relevant to multiple health behaviors and should be considered when designing health promotion for older adults, including interventions for dementia risk reduction. Findings highlight the importance of distinguishing apathy from comorbid symptoms. Highlights: Novel theory-based perspective on behavioural risk factors for dementia. Higher apathy predicted less physical activity and alcohol use, and increased odds of lifestyle risk factors. Depressive symptoms were not associated with any health behavior. Apathy may be a determinant of multiple health behaviors in older adults, distinct from depression and fatigue. Considering apathy in precision prevention of dementia appears warranted

Computer-aided extraction of select MRI markers of cerebral small vessel disease: A systematic review

Cerebral small vessel disease (CSVD) is a major vascular contributor to cognitive impairment in ageing, including dementias. Imaging remains the most promising method for in vivo studies of CSVD. To replace the subjective and laborious visual rating approaches, emerging studies have applied state-of-the-art artificial intelligence to extract imaging biomarkers of CSVD from MRI scans. We aimed to summarise published computer-aided methods for the examination of three imaging biomarkers of CSVD, namely cerebral microbleeds (CMB), dilated perivascular spaces (PVS), and lacunes of presumed vascular origin. Seventy classical image processing, classical machine learning, and deep learning studies were identified. Transfer learning and weak supervision techniques have been applied to accommodate the limitations in the training data. While good performance metrics were achieved in local datasets, there have not been generalisable pipelines validated in different research and/or clinical cohorts. Future studies could consider pooling data from multiple sources to increase data size and diversity, and evaluating performance using both image processing metrics and associations with clinical measures

Is intraindividual reaction time variability an independent cognitive predictor of mortality in old age? Findings from the Sydney Memory and Ageing Study

Intraindividual variability of reaction time (IIVRT), a proposed cognitive marker of neurobiological disturbance, increases in old age, and has been associated with dementia and mortality. The extent to which IIVRT is an independent predictor of mortality, however, is unclear. This study investigated the association of IIVRT and all-cause mortality while accounting for cognitive level, incident dementia and biomedical risk factors in 861 participants aged 70–90 from the Sydney Memory and Ageing Study. Participants completed two computerised reaction time (RT) tasks (76 trials in total) at baseline, and comprehensive medical and neuropsychological assessments every 2 years. Composite RT measures were derived from the two tasks—the mean RT and the IIVRT measure computed from the intraindividual standard deviation of the RTs (with age and time-on-task effects partialled out). Consensus dementia diagnoses were made by an expert panel of clinicians using clinical criteria, and mortality data were obtained from a state registry. Cox proportional hazards models estimated the association of IIVRT and mean RT with survival time over 8 years during which 191 (22.2%) participants died. Greater IIVRT but not mean RT significantly predicted survival time after adjusting for age, sex, global cognition score, cardiovascular risk index and apolipoprotein ɛ4 status. After excluding incident dementia cases, the association of IIVRT with mortality changed very little. Our findings suggest that greater IIVRT uniquely predicts shorter time to death and that lower global cognition and prodromal dementia in older individuals do not explain this relationship

Instrumental Activities of Daily Living by Subjective and Objective Measures: The Impact of Depression and Personality

Objective: Previous research shows that depression and personality are independently associated with self- and informant-reports of the ability to perform instrumental activities of daily living (IADLs). However, less is known about the association between depression and personality and performance-based measures of IADLs. We aimed to determine how depression and personality predict self-and informant-reports of IADL compared to performance-based measures of IADLs in a sample of older adults with normal cognition (NC) and Mild Cognitive Impairment (MCI). Methods: Participants consisted of 385 older adults with NC (n = 235), or a diagnosis of MCI (n = 150), aged between 76 and 99-years from the Sydney Memory and Ageing Study. Participants underwent comprehensive neuropsychological and clinical assessments to determine global cognition and clinical diagnoses. Personality traits were measured by the NEO Five-Factor Inventory (NEO-FFI) and depression by the Geriatric Depression Scale (GDS). Subjective IADLs were self- and informant-reported Bayer Activities of Daily Living (B-ADL) scales and objective IADL was the Sydney Test of Activities of Daily Living in Memory Disorders (STAM). Linear regressions examined the relationship between depression and personality and the three types of IADL measures, controlling for all covariates and global cognition. Results: Participant-reported IADL, although associated with global cognition, was more strongly associated with GDS and NEO-FFI scores (conscientiousness and neuroticism). Informant-reported IADL was strongly associated with both global cognition and participants’ GDS scores. STAM scores were not associated with participants’ GDS or NEO-FFI scores; instead, they were predicted by demographics and global cognition. Conclusion: These results suggest that performance-based measures of IADL may provide more objective and reliable insight into an individual’s underlying functional ability and are less impacted by the participants’ mood and personality compared to subjectively reported IADL. We argue that performance-based IADL measures are preferable when trying to accurately assess everyday functional ability and its relationship to cognitive status. Where performance-based measures are not available (e.g., in some clinical settings), informant ratings should be sought as they are less influenced by the participant’s personality and mood compared to self-reports

Reaction Time Measures Predict Incident Dementia in Community-Living Older Adults: The Sydney Memory and Ageing Study

Objective To examine the utility of intraindividual variability of reaction times (IIVRT) and mean reaction time (RT) as behavioral markers of incident all-cause dementia. Methods A longitudinal cohort study followed biennially for 4 years, the community-based Sydney Memory and Ageing Study, 861 initially nondemented participants aged 70–90. Incident all-cause dementia determined by consensus, RT measures from simple and complex tasks, Mini-Mental State Exam and neuropsychological tests, Geriatric Depression Scale and Goldberg Anxiety Scale, cardiovascular risk score, apolipoprotein ε4 status, and the Bayer ADL Scale were used. Associations of baseline IIVRT and mean RT with time to dementia were evaluated with hazard ratios (HRs) using Cox proportional-hazards models with and without controlling for dementia risk factors. Results Forty-eight cases developed dementia. Greater complex IIVRT predicted a 40% (HR: 1.43) and mean RT a 50%–60% (simple RT: HR 1.53; complex RT: HR 1.59) per standard deviation increased risk of developing dementia, remaining significant after controlling for age, education, sex, general cognitive function, mood, cerebrovascular disease, and genetic susceptibility. Prediction of incident dementia using demographical information and RT measures combined was comparable with several traditional neuropsychological measures (AUC 0.75), although lower than a full neuropsychological battery (AUC 0.90). Prediction of functional decline by RT measures combined was equal to the neuropsychological battery (multiple Rs of .233 and .238, respectively). Conclusion Brief RT measures provided information on risk of imminent dementia and functional decline within 4 years in older adults at a population level, with mean RT the stronger predictor

Post-Stroke Brain Health Monitoring and Optimization: A Narrative Review

Significant advancements have been made in recent years in the acute treatment and secondary prevention of stroke. However, a large proportion of stroke survivors will go on to have enduring physical, cognitive, and psychological disabilities from suboptimal post-stroke brain health. Impaired brain health following stroke thus warrants increased attention from clinicians and researchers alike. In this narrative review based on an open timeframe search of the PubMed, Scopus, and Web of Science databases, we define post-stroke brain health and appraise the body of research focused on modifiable vascular, lifestyle, and psychosocial factors for optimizing post-stroke brain health. In addition, we make clinical recommendations for the monitoring and management of post-stroke brain health at major post-stroke transition points centered on four key intertwined domains: cognition, psychosocial health, physical functioning, and global vascular health. Finally, we discuss potential future work in the field of post-stroke brain health, including the use of remote monitoring and interventions, neuromodulation, multi-morbidity interventions, enriched environments, and the need to address inequities in post-stroke brain health. As post-stroke brain health is a relatively new, rapidly evolving, and broad clinical and research field, this narrative review aims to identify and summarize the evidence base to help clinicians and researchers tailor their own approach to integrating post-stroke brain health into their practices

Systemic Inflammation Predicts Alzheimer Pathology in Community Samples without Dementia

Neuroinflammation and oxidative stress (OS) are implicated in the pathophysiology of Alzheimer’s disease (AD). However, it is unclear at what stage of the disease process inflammation first becomes manifest. The aim of this study was to investigate the associations between specific plasma markers of inflammation and OS, tau, and Amyloid-β 38, 40, and 42 levels in cognitively unimpaired middle-age and older individuals. Associations between inflammatory states identified through principal component analysis and AD biomarkers were investigated in middle-age (52–56 years, n = 335, 52% female) and older-age (72–76 years, n = 351, 46% female) participants without dementia. In middle-age, a component reflecting variation in OS was most strongly associated with tau and to a lesser extent amyloid-β levels. In older-age, a similar component to that observed in middle-age was only associated with tau, while another component reflecting heightened inflammation independent of OS, was associated with all AD biomarkers. In middle and older-age, inflammation and OS states are associated with plasma AD biomarkers

Diastolic Blood Pressure Variability in Later Life May Be a Key Risk Marker for Cognitive Decline

BACKGROUND: There is an increasing awareness of the need to understand the interaction between long-term blood pressure patterns and their impact on the brain and cognition. METHODS: Our aim was to investigate the relationship between repeated blood pressure measures and change in cognitive performance over 12 years and imaging data at 12 years using a longitudinal population study. The data consisted of 2 cohorts, one midlife and one later life. Using linear regression, we examined the relationship between blood pressure (systolic, diastolic, change in blood pressure between visits, and visit-to-visit variability), change in cognitive performance and imaging at 12 years. RESULTS: Data on cognitive change were available in 1054 at midlife, baseline age 42.7 (SD 1.5) and 1233 in later life, 62.5 (1.5) years. Imaging data were available in 168 and 233, respectively. After adjustment for multiple comparisons greater diastolic blood pressure variability in later life was associated with a −1.95 point decline (95% CI, −2.89 to −1.01) on an attention-based task and a −0.42 point (95% CI, −0.68 to −0.15) decline in performance on a psychomotor task. A higher SD in diastolic pressure across follow-up was associated with greater white matter hyperintensity volume (%increase per 10 mmHg increase in the SD [1.50 (95% CI, 1.16–1.94]). CONCLUSIONS: In a largely normotensive/mildly hypertensive population, our analyses reported no relationships between blood pressure and cognition in midlife but a potential role for diastolic blood pressure variability in later life as a risk marker for cognitive decline. This may indicate an at-risk period or a means to identify an at-risk population at the age where diastolic pressure is starting to decline

Intraindividual Stepping Reaction Time Variability Predicts Falls in Older Adults With Mild Cognitive Impairment

Background: Reaction time measures have considerable potential to aid neuropsychological assessment in a variety of health care settings. One such measure, the intraindividual reaction time variability (IIV), is of particular interest as it is thought to reflect neurobiological disturbance. IIV is associated with a variety of age-related neurological disorders, as well as gait impairment and future falls in older adults. However, although persons diagnosed with Mild Cognitive Impairment (MCI) are at high risk of falling, the association between IIV and prospective falls is unknown. Methods: We conducted a longitudinal cohort study in cognitively intact (n = 271) and MCI (n = 154) community-dwelling adults aged 70–90 years. IIV was assessed through a variety of measures including simple and choice hand reaction time and choice stepping reaction time tasks (CSRT), the latter administered as a single task and also with a secondary working memory task. Results: Logistic regression did not show an association between IIV on the hand-held tasks and falls. Greater IIV in both CSRT tasks, however, did significantly increase the risk of future falls. This effect was specific to the MCI group, with a stronger effect in persons exhibiting gait, posture, or physiological impairment. Conclusions: The findings suggest that increased stepping IIV may indicate compromised neural circuitry involved in executive function, gait, and posture in persons with MCI increasing their risk of falling. IIV measures have potential to assess neurobiological disturbance underlying physical and cognitive dysfunction in old age, and aid fall risk assessment and routine care in community and health care settings

Biocompatibility and proteomic profiling of DMSA-coated iron nanocubes in a human glioblastoma cell line

Background: Superparamagnetic iron core iron oxide shell nanocubes have previously shown superior performance in magnetic resonance imaging T2 contrast enhancement compared with spherical nanoparticles. Methods: Iron core iron oxide shell nanocubes were synthesized, stabilized with dimercaptosuccinic acid (DMSA-NC) and physicochemically characterized. MRI contrast enhancement and biocompatibility were assessed in vitro. Results: DMSA-NC showed a transverse relaxivity of 122.59 mM-1·s-1 Fe. Treatment with DMSA-NC did not induce cytotoxicity or oxidative stress in U-251 cells, and electron microscopy demonstrated DMSA-NC localization within endosomes and lysosomes in cells following internalization. Global proteomics revealed dysregulation of iron storage, transport, transcription and mRNA processing proteins. Conclusion: DMSA-NC is a promising T2 MRI contrast agent which, in this preliminary investigation, demonstrates favorable biocompatibility with an astrocyte cell model. Plain language summary: MRI is a powerful tool used in the diagnosis of cancer, strokes and other injuries. An MRI scan can be improved with the use of iron oxide nanoparticles, which enhance the contrast of the image. In this study we have developed cube-shaped iron nanoparticles (nanocubes), which have been previously shown to be more effective at inducing contrast. We demonstrated that iron-based nanocubes do not damage or induce stress in cells and work effectively as an MRI contrast agent. We further analyzed how the nanocubes may affect cell functioning by investigating changes to protein levels in the cells. The results of this study are promising steps towards using iron-based nanocubes as a tool to improve the clarity of MRI scans for medical imaging and diagnosis. Future work must determine whether these nanocubes work effectively and safely in an animal model, which is a critical step in progressing to their use in clinical settings