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Sex differences in late-life memory decline may be explained by sex differences in dementia risk factors. Episodic memory and dementia risk factors were assessed in young, middle-aged and older adults over 12 years in a population-based sample (N = 7485). For men in midlife and old age, physical, cognitive and social activities were associated with less memory decline, and financial hardship was associated with more. APOE e4 and vascular risk factors were associated with memory decline for women in midlife. Depression, cognitive and physical activity were associated with memory change in older women. Incident midlife hypertension (β = − 0.48, 95% CI − 0.87, − 0.09, p = 0.02) was associated with greater memory decline in women and incident late-life stroke accounted for greater memory decline in men (β = − 0.56, 95% CI − 1.12, − 0.01), p = 0.05). Women have fewer modifiable risk factors than men. Stroke and hypertension explained sex differences in memory decline for men and women respectively.

Background Neuropsychiatric symptoms (NPS) are common in individuals with Alzheimer’s disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia. Methods Literature searches were conducted in Embase, MEDLINE/PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar from inception to February 2021. Study selection, data extraction, and quality assessment were conducted in duplicate. Effect sizes were calculated as odds ratios (OR) for NPS prevalence and Hedges’ g for NPS severity. Data were pooled using random-effects models. Sources of heterogeneity were examined using meta-regression analyses. Results Sixty-two studies were eligible representing 21,554 patients (61.2% females). The majority of the included studies had an overall rating of fair quality (71.0%), with ten studies of good quality (16.1%) and eight studies of poor quality (12.9%). There was no sex difference in the presence of any NPS ( k = 4, OR = 1.35 [95% confidence interval 0.78, 2.35]) and overall NPS severity ( k = 13, g = 0.04 [− 0.04, 0.12]). Regarding specific symptoms, female sex was associated with more prevalent depressive symptoms ( k = 20, OR = 1.60 [1.28, 1.98]), psychotic symptoms (general psychosis k = 4, OR = 1.62 [1.12, 2.33]; delusions k = 12, OR = 1.56 [1.28, 1.89]), and aberrant motor behavior ( k = 6, OR = 1.47 [1.09, 1.98]). In addition, female sex was related to more severe depressive symptoms ( k = 16, g = 0.24 [0.14, 0.34]), delusions ( k = 10, g = 0.19 [0.04, 0.34]), and aberrant motor behavior ( k = 9, g = 0.17 [0.08, 0.26]), while apathy was more severe among males compared to females ( k = 11, g = − 0.10 [− 0.18, − 0.01]). There was no association between sex and the prevalence and severity of agitation, anxiety, disinhibition, eating behavior, euphoria, hallucinations, irritability, and sleep disturbances. Meta-regression analyses revealed no consistent association between the effect sizes across studies and method of NPS assessment and demographic and clinical characteristics. Discussion Female sex was associated with a higher prevalence and greater severity of several specific NPS, while male sex was associated with more severe apathy. While more research is needed into factors underlying these sex differences, our findings may guide tailored treatment approaches of NPS in AD dementia.

Physical activity shows promise for reduced risk of Alzheimer's disease (AD) and protection against cognitive decline among individuals with and without AD. Older adults face many barriers to adoption of physically active lifestyles and people with AD face even further challenges. Physical activity is a promising non-pharmacological approach to improve depressive symptoms, but little is known about the impact of depressive symptoms as a potential barrier to engagement in physical activity. The present study aimed to investigate depressive symptoms as a potential barrier for participation in physical activity across a range of dementia severity. We used longitudinal structural equation modelling to investigate the bi-directional relationship between depressive symptoms and physical activity in 594 older adults with and without AD over a 2 year longitudinal follow up. Participants ranged from no cognitive impairment to moderately severe AD. We found that depressive symptoms predicted reduced engagement in subsequent physical activity, but physical activity did not predict subsequent reductions in depressive symptoms. We conclude that depressive symptoms may be an important barrier to engagement in physical activity that may be addressed in clinical practice and intervention research.

Background At the outbreak of the pandemic in Australia, which directly followed unprecedented bushfires, the PATH Through Life Study had just commenced data collection of its 5th wave for the 40s age cohort. Continuation of fieldwork required dynamic transition from an in-person structured assessment protocol, to remote assessment methods with adaptation of established measures. We aim to describe the methods used to adapt the longitudinal study to these events, and the implications of data collection methodology for analysis. Reflections on these experiences are essential for transparent reporting of protocol change, and for informing future study design. Methods Evaluation of the data collection process for the fifth follow-up assessment of the PATH Through Life Study, a population-based cohort of Australians aged 58–64 years ( n  = 2530). Evaluation metrics include response rates for interviews done in-person and remotely, observations from data collection modifications, and participant feedback. Additional online survey items measuring the impact of exposure to bushfires and COVID-19 were developed and deployed as part of the study. Results Of 2147 contacted for follow-up, 1558 participants completed wave 5 (data collection commenced September 2019). By November 2019 (onset of the bushfires), 585 (37%) participants had completed face-to-face interviews and by March 2020, a further 1057 (68%) participants had completed their interviews at the onset of government restrictions relating to COVID-19. The shift to remote assessments resulted in 30% of assessments being completed by telephone. Challenges of the data protocol approach are discussed including the impact of multiple data collection pathways on analysis, and limitations of telephone interviews. Participant completion rates for the additional bushfire and COVID-19 surveys for the wave were 60% and 69% respectively; anecdotal participant feedback was positive regarding the inclusion of these measures. Conclusions Dynamic capture of exposure to unexpected events within the context of an established longitudinal study requires rapid design and protocol adaptations, and careful documentation of participation timing and pathways. Given the heightened public interest, participant response was encouraging, and the data captured not only enhances the value of the whole dataset, but is uniquely placed to address questions on population-level vulnerabilities and ongoing impacts of the exposures.

Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes. This study aimed to determine whether blood glucose levels in the normal range (<6.1 mmol/L) were associated with cerebral volumes in structures other than the hippocampus and amygdale, and whether these glucose-related regional volumes were associated with cognitive performance. 210 cognitively healthy individuals (68-73 years) without diabetes, glucose intolerance or metabolic syndrome were assessed in the large, community-based Personality and Total Health Through Life (PATH) study. Baseline blood glucose levels in the normal range (3.2-6.1 mmol/l) were used to determine regional brain volumes and associated cognitive function at wave 3. Higher blood glucose levels in the normal range were associated with lower grey/white matter regional volumes in the frontal cortices (middle frontal gyrus, inferior frontal gyrus precentral gyrus). Moreover, identified cerebral regions were associated with poorer cognitive performance and the structure-function associations were gender specific to men. These findings stress the need to re-evaluate what is considered as healthy blood glucose levels, and consider the role of higher normal blood glucose as a risk factor for cerebral health, cognitive function and dementia. A better lifetime management of blood glucose levels may contribute to improved cerebral and cognitive health in later life and possibly protect against dementia.

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.

Background There is little information on the application and impact of revised criteria for diagnosing dementia and mild cognitive impairment (MCI), now termed major and mild neurocognitive disorders (NCDs) in the DSM-5. We evaluate a psychometric algorithm for diagnosing DSM-5 NCDs in a community-dwelling sample, and characterize the neuropsychological and functional profile of expert-diagnosed DSM-5 NCDs relative to DSM-IV dementia and International Working Group criteria for MCI. Methods A population-based sample of 1644 adults aged 72–78 years was assessed. Algorithmic diagnostic criteria used detailed neuropsychological data, medical history, longitudinal cognitive performance, and informant interview. Those meeting all criteria for at least one diagnosis had data reviewed by a neurologist (expert diagnosis) who achieved consensus with a psychiatrist for complex cases. Results The algorithm accurately classified DSM-5 major NCD (area under the curve (AUC) = 0.95, 95% confidence interval (CI) 0.92–0.97), DSM-IV dementia (AUC = 0.91, 95% CI 0.85–0.97), DSM-5 mild NCD (AUC = 0.75, 95% CI 0.70–0.80), and MCI (AUC = 0.76, 95% CI 0.72–0.81) when compared to expert diagnosis. Expert diagnosis of dementia using DSM-5 criteria overlapped with 90% of DSM-IV dementia cases, but resulted in a 127% increase in diagnosis relative to DSM-IV. Additional cases had less severe memory, language impairment, and instrumental activities of daily living (IADL) impairments compared to cases meeting DSM-IV criteria for dementia. DSM-5 mild NCD overlapped with 83% of MCI cases and resulted in a 19% increase in diagnosis. These additional cases had a subtly different neurocognitive profile to MCI cases, including poorer social cognition. Conclusion DSM-5 NCD criteria can be operationalized in a psychometric algorithm in a population setting. Expert diagnosis using DSM-5 NCD criteria captured most cases with DSM-IV dementia and MCI in our sample, but included many additional cases suggesting that DSM-5 criteria are broader in their categorization.

INTRODUCTION Changes to the brain due to Alzheimer's disease and other age‐related neuropathologies may present with cognitive and behavioral symptoms, even during preclinical and prodromal stages. While cognitive reserve is known to mitigate cognitive decline in the preclinical stages of Alzheimer's disease, links between cognitive reserve and behavioral symptoms remain unclear. This study investigates the relationship between cognitive reserve and mild behavioral impairment (MBI), a neurodegenerative behavioral prodrome. METHODS We analyzed cross‐sectional data from 1204 participants in the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN‐PROTECT) study. A cognitive reserve score (CRS) was generated based on education, occupation, and personal cognitive reserve proxies. MBI presence (MBI+) and MBI global and domain symptom severity were evaluated using the self‐reported MBI Checklist. Initial analyses examined the convergent validity of the CRS through associations with objective neuropsychological test performance and self‐reported cognitive symptoms (Everyday Cognition [ECog‐II] scale). Models were also fitted to assess MBI status and severity as functions of the CRS. RESULTS Higher CRS was associated with better neuropsychological test scores, lower odds of subjective cognitive decline (OR = 0.86, 95% CI: [0.76, 0.98], p = .03), and lower ECog‐II total score. Likewise, higher CRS was associated with lower odds of MBI+ (OR = 0.81, 95% CI: [0.71, 0.93], p = .003), and lower MBI symptom severity globally, and in impulse dyscontrol and social inappropriateness domains. DISCUSSION We provide preliminary evidence that engagement in activities known to preserve cognitive function in aging and disease may also preserve behavioral function. Future research should disentangle possible pathways through which cognitive reserve may preserve both cognition and behavior, explore common etiologies for these symptoms, and observe outcomes longitudinally to better understand these relationships. Highlights Education, occupation, and personal activities are cognitive reserve proxies. Cognitive reserve is linked to lower subjective cognitive decline in older persons. Cognitive reserve is linked to lower mild behavioral impairment odds and severity.

A dearth of population-based epidemiological research examines neuropsychiatric symptom (NPS) in sub-clinical populations across the spectrum from normal aging to mild cognitive impairment (MCI). The construct of mild behavioral impairment (MBI) describes the emergence of sustained and impactful NPS in advance of or in combination with MCI. This is the first epidemiological study to operationalize the recently published diagnostic criteria for MBI and determine prevalence estimates across the spectrum from cognitively normal to MCI. MBI was assessed in 1,377 older (age range 72–79 years; 52% male; MCI ;= 133; cognitively normal, but-at-risk = 397; cognitively healthy = 847). MBI was assessed in accordance with the ISTAART-AA diagnostic criteria for MBI using the neuropsychiatric inventory. 34.1% of participants met the criteria for MBI. High prevalence of MBI across the cognitive spectrum was reported (48.9% vs. 43.1% vs. 27.6%). Irrespective of level of cognitive impairment, impulse dyscontrol (33.8% vs. 28.7% vs. 17.2%) and decreased motivation (32.3% vs. 26.2% vs. 16.3%) were the most frequently met MBI domains. MBI was more prevalent in men (χ2 = 4.98, p = 0.026), especially the domains of decreased motivation and impulse dyscontrol. This study presents the first population-based prevalence estimates for MBI using the recently published ISTAART-AA diagnostic criteria. Findings indicate relatively high prevalence of MBI in pre-dementia clinical states and amongst cognitively healthy older adults. Findings were gender-specific, with MBI affecting more men than women. Knowing the estimates of these symptoms in the population is essential for understanding and differentiating the very early development of clinical disorders.

Affective and emotional symptoms such as depression, anxiety, euphoria, and irritability are common neuropsychiatric symptoms (NPS) in pre-dementia and cognitively normal older adults. They comprise a domain of Mild Behavioral Impairment (MBI), which describes their emergence in later life as an at-risk state for cognitive decline and dementia, and as a potential manifestation of prodromal dementia. This selective scoping review explores the epidemiology and neurobiological links between affective and emotional symptoms, and incident cognitive decline, focusing on recent literature in this expanding field of research. Existing literature in prodromal and dementia states was reviewed, focusing on epidemiology, and neurobiology. Search terms included: “mild cognitive impairment,” “dementia,” “prodromal dementia,” “preclinical dementia,” “Alzheimer's,” “depression,” “dysphoria,” “mania,” “euphoria,” “bipolar disorder,” and “irritability.” Affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often being harbingers of neurodegenerative change and progressive cognitive decline. Nosological constraints in distinguishing between pre-existing psychiatric symptomatology and later life acquired NPS limit historical data utility, but emerging research emphasizes the importance of addressing time frames between symptom onset and cognitive decline, and age of symptom onset. Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies.