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Suicide has been identified as a leading cause of premature death in autistic populations. Elevated autistic traits have also been associated with higher rates of self-harm, suicidal ideation, and suicidal self-harm in the general population, but this has yet to be examined in older age. Using baseline cross-sectional data from the PROTECT study, middle-age and older adults with high autistic traits (n = 276) had significantly higher rates of suicidal ideation, deliberate self-harm, and suicidal self-harm than an age/sex-matched comparison group (n = 10,495). These differences represented a 5- to 6-fold increase in likelihood for self-harming and suicidality. These findings, which remained when controlling for depression symptoms, suggest that middle-age and older adults with high autistic traits may be particularly at risk of self-harm and suicidal behaviours.

Apathy is one of the most common neuropsychiatric symptoms (NPS) and is associated with poor clinical outcomes. Research that helps define the apathy phenotype is urgently needed, particularly for clinical and biomarker studies. We used latent class analysis (LCA) with two independent cohorts to understand how apathy and depression symptoms co-occur statistically. We further explored the relationship between latent class membership, demographics, and the presence of other NPS. The LCA identified a four-class solution (no symptoms, apathy, depression, and combined apathy/depression), reproducible over both cohorts, providing robust support for an apathy syndrome distinct from depression and confirming that an apathy/depression syndrome exists, supported by the model fit test with the four-class solution scores evidencing better fitting (Bayesian information criterion adjusted and entropy R 2). Using a data-driven method, we show distinct and statistically meaningful co-occurrence of apathy and depressive symptoms. There was evidence that these classes have different clinical associations, which may help inform diagnostic categories for research studies and clinical practice.HighlightsWe found four classes: no symptoms, apathy, depression and apathy/depression.Apathy conferred a higher probability for agitation.Apathy diagnostic criteria should include accompanying neuropsychiatric symptoms.

Suicide has been identified as a leading cause of premature death in autistic populations. Elevated autistic traits have also been associated with higher rates of self-harm, suicidal ideation, and suicidal self-harm in the general population, but this has yet to be examined in older age. Using baseline cross-sectional data from the PROTECT study, middle-age and older adults with high autistic traits (n = 276) had significantly higher rates of suicidal ideation, deliberate self-harm, and suicidal self-harm than an age/sex-matched comparison group (n = 10,495). These differences represented a 5- to 6-fold increase in likelihood for self-harming and suicidality. These findings, which remained when controlling for depression symptoms, suggest that middle-age and older adults with high autistic traits may be particularly at risk of self-harm and suicidal behaviours., Author(s): Gavin R. Stewart [sup.1] , Anne Corbett [sup.2] , Clive Ballard [sup.2] , Byron Creese [sup.2] , Dag Aarsland [sup.1] , Adam Hampshire [sup.3] , Rebecca A. Charlton [sup.4] [...]

Psychosis is a common and distressing symptom in people with Alzheimer disease, and few safe and effective treatments are available. However, new approaches to symptom assessment and treatment are beginning to drive the field forward. New nosological perspectives have been provided by incorporating the emergence of psychotic symptoms in older adults - even in advance of dementia - into epidemiological and neurobiological frameworks as well as into diagnostic and research criteria such as the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders, the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) research criteria for psychosis in neurodegenerative disease, and the ISTAART criteria for mild behavioural impairment. Here, we highlight the latest findings in genomics, neuroimaging and neurobiology that are informing approaches to drug discovery and repurposing. Current pharmacological and non-pharmacological treatment options are discussed, with a focus on safety and precision medicine. We also explore trial data for pimavanserin, a novel agent that shows promise for the treatment of psychosis in people with dementia, and discuss existing agents that might be useful but need further exploration such as escitalopram, lithium, cholinesterase inhibitors and vitamin D. Although the assessment and management of psychosis in people with dementia remain challenging, new opportunities are providing direction and hope to the field.

Purpose of reviewTo review the incidence, treatment and genetics of psychosis in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD).Recent findingsPsychosis in Alzheimer's disease (AD) has an incidence of ~ 10% per year. There is limited evidence regarding psychological interventions. Pharmacological management has focused on atypical antipsychotics, balancing modest benefits with evidence of long-term harms. The 5HT2A inverse agonist pimavanserin appears to confer benefit in PD psychosis with initial evidence of benefit in AD. Cholinesterase inhibitors give modest benefits in DLB psychosis. The utility of muscarinic agonists, lithium, glutamatergic and noradrenergic modulators needs further study. Recent work has confirmed the importance of psychosis in MCI as well as AD. The lack of evidence regarding psychological therapies is an urgent knowledge gap, but there is encouraging evidence for emerging pharmacological treatments. Genetics will provide an opportunity for precision medicine and new treatment targets.

BackgroundPsychotic symptoms are common in Alzheimer's disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice.ObjectiveTo establish research criteria for the diagnosis of psychosis in AD.MethodsThe International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria.ResultsConsensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders, 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers.ConclusionWe propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders.

Physical inactivity in mid-life is a modifiable risk factor for dementia. Mild behavioral impairment (MBI) is a marker of potential neurodegenerative disease. We investigated the association between physical activity and MBI. Baseline data from the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behaviour, Function, and Caregiving in Aging (CAN-PROTECT) were used. Four categories of weekly physical activity (cardiovascular, mind-body, strength training, and physical labour) were derived from the Community Healthy Activities Model Program for Seniors questionnaire. MBI was measured using the MBI-Checklist. Multivariable negative binomial regressions modelled the association between the standardized physical activity duration and MBI severity, adjusted for age, sex, education, marital status, ethno cultural origin, occupation, hypertension, dyslipidemia, mobility, and body mass index. Every 1 SD increase in cardiovascular activity was associated with 8.42% lower MBI severity. In contrast, every 1 SD increase in physical labor duration was associated with 5.64% greater MBI severity. These associations were neither moderated by the frequency engaging in each physical activity nor by sex. Cardiovascular physical activity in older persons may reduce levels of non-cognitive dementia markers like MBI, comparable to effects seen in cognition, potentially modulating dementia risk. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes. METHODS: Genome‐wide association meta‐analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P). RESULTS: AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations. DISCUSSION: AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development. Highlights: It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not.Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations. [ABSTRACT FROM AUTHOR]

The amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer's disease in the seminal 1991 article by Braak and Braak. This knowledge has, however, only received traction recently with advances in imaging and image analysis techniques. Here, we provide a cross-disciplinary overview of pathology and neuroimaging studies on the amygdala. These studies provide strong support for an early role of the amygdala in Alzheimer's disease and the utility of imaging biomarkers of the amygdala in detecting early changes and predicting decline in cognitive functions and neuropsychiatric symptoms in early stages. We summarize the animal literature on connectivity of the amygdala, demonstrating that amygdala nuclei that show the earliest and strongest accumulation of neurofibrillary tangle pathology are those that are connected to brain regions that also show early neurofibrillary tangle accumulation. Additionally, we propose an alternative pathway of neurofibrillary tangle spreading within the medial temporal lobe between the amygdala and the anterior hippocampus. The proposed existence of this pathway is strengthened by novel experimental data on human functional connectivity. Finally, we summarize the functional roles of the amygdala, highlighting the correspondence between neurofibrillary tangle accumulation and symptomatic profiles in Alzheimer's disease. In summary, these findings provide a new impetus for studying the amygdala in Alzheimer's disease and a unique perspective to guide further study on neurofibrillary tangle spreading and the occurrence of neuropsychiatric symptoms in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: The accumulation of age‐associated cognitive deficits can lead to Mild Cognitive Impairment (MCI) and dementia. This is a major public health issue for the modern ageing population, as it impairs health, independence and overall quality of life. Keeping the brain active during life has been associated with an increased cognitive reserve, therefore reducing the risk of cognitive impairment in older age. Previous research has identified a potential relationship between musicality and cognition. Objectives: Explore the relationship between musicality and cognitive function in a large cohort of older adults. Methods: This was a nested study within the PROTECT‐UK cohort, which collects longitudinal computerised assessments of cognitive function in adults over 40. Participants were invited to complete the validated Edinburgh Lifetime Musical Experience Questionnaire (ELMEQ) to assess their musical experience and lifetime exposure to music. Linear regression analysis was performed using cognitive data from PROTECT‐UK. Results: Analysis identified an association between musicality and cognition in this cohort. Playing a musical instrument was associated with significantly better performance in working memory and executive function. Significant associations were also found between singing and executive function, and between overall musical ability and working memory. Conclusions: Our findings confirm previous literature, highlighting the potential value of education and engagement in musical activities throughout life as a means of harnessing cognitive reserve as part of a protective lifestyle for brain health. Key points: Playing a musical instrument was associated with significantly better working memory and executive function.Singing and overall musical ability was associated with more favourable cognition.Engagement with musical activities should be considered as part of public health initiatives to promote a protective lifestyle for brain health. [ABSTRACT FROM AUTHOR]

Objective: Sleep is vital for normal cognitive function in daily life, but is commonly disrupted in older adults. Poor sleep can be detrimental to mental and physical health, including cognitive function. This study assessed the association between self‐reported short (<6 h) and long (>9 h) sleep duration and sleep fragmentation (3≥ nightly awakenings) in cognitive function. Methods: Cross‐sectional data from 8508 individuals enroled in the PROTECT study aged 50 and above formed the basis of the univariate linear regression analysis conducted on four cognitive outcomes assessing visuospatial episodic memory (VSEM), spatial working memory, verbal working memory (VWM), and verbal reasoning (VR). Results: Short (ß = −0.153, 95% CI [−0.258, −0.048], p = 0.004) and long sleep duration (ß = −0.459, 95% CI [−0.826, −0.091], p = 0.014) were significantly associated with poorer cognitive performance in VWM. Long sleep duration (ß = −2.986, 95% CI [−5.453, −0.518], p = 0.018) was associated with impaired VR. Short sleep (ß = −0.133, 95% CI [−0.196, −0.069], p = <0.001) and sleep fragmentation (ß = −0.043, 95% CI [−0.085, −0.001], p = 0.043) were associated with reduced VSEM. These associations remained significant when including other established risk factors for dementia and cognitive decline (e.g., depression, hypertension). Conclusions: Our findings suggest that short and long sleep durations and fragmented sleep, may be risk factors for a decline in cognitive processes such as working memory, VR and episodic memory thus might be potential targets for interventions to maintain cognitive health in ageing. Key points: This study assessed the association between self‐reported short (<6 h) and long (>9 h) sleep duration and sleep fragmentation (3 or more nightly awakenings) in cognitive function.Univariate linear regression analysis indicated that short and long sleep duration, and sleep fragmentation impaired cognitive processes such as working memory, verbal reasoning (VR) and episodic memory in individuals aged 50+, even when including other established risk factors for dementia and cognitive decline, such as low educational level, hearing loss, traumatic brain injury, hypertension, diabetes, alcohol consumption, obesity, smoking, depression, social isolation, and physical inactivity.Both sleep duration and sleep fragmentation are highlighted as potential risk factors for reduced cognitive function and might be a possible target for interventions to maintain cognitive health in ageing. [ABSTRACT FROM AUTHOR]

Introduction: Late‐life onset psychosis is associated with faster progression to dementia in cognitively normal people, but little is known about its relationship with cognitive impairment in advance of dementia. Methods: Clinical and genetic data from 2750 people ≥50 years of age without dementia were analyzed. Incident cognitive impairment was operationalized using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and psychosis was rated using the Mild Behavioral Impairment Checklist (henceforth MBI‐psychosis). The whole sample was analyzed before stratification on apolipoprotein E (APOE) ε4 status. Results: In Cox proportional hazards models, MBI‐psychosis had a higher hazard for cognitive impairment relative to the No Psychosis group (hazard ratio [HR]: 3.6, 95% confidence interval [CI]: 2.2–6, p < 0.0001). The hazard for MBI‐psychosis was higher in APOE ε4 carriers and there was an interaction between the two (HR for interaction: 3.4, 95% CI: 1.2–9.8, p = 0.02). Discussion: Psychosis assessment in the MBI framework is associated with incident cognitive impairment in advance of dementia. These symptoms may be particularly important in the context of APOE genotype. [ABSTRACT FROM AUTHOR]

Cognitive differences in memory, information processing speed (IPS), and executive functions (EF), are common in autistic and high autistic trait populations. Despite memory, IPS and EF being sensitive to age‐related change, little is known about the cognitive profile of older adults with high autistic traits. This study explores cross‐sectional memory, IPS and EF task performance in a large sample of older adults in the online PROTECT cohort (n = 22,285, aged 50–80 years), grouped by high vs. low autistic traits. Approximately 1% of PROTECT participants (n = 325) endorsed high autistic traits [henceforth Autism Spectrum Trait (AST) group]. Differences between AST and age‐, gender‐, and education‐matched comparison older adults (COA; n = 11,744) were explored on memory, IPS and EF tasks and questionnaires administered online. AST had lower performance than COA on tasks measuring memory, working memory, sustained attention, and information processing. No group differences were observed in simple attention or verbal reasoning. A similar pattern of results was observed when controlling for age, and current depression and anxiety symptoms. In addition, AST self‐reported more cognitive decline than COA, but this difference was not significant when controlling for current depression symptoms, or when using informant‐report. These findings suggest that autistic traits are associated with cognitive function in middle‐aged and later life. Older adults with high autistic traits experienced more performance difficulties in a range of memory, IPS and EF tasks compared with the low autistic traits comparison group. Further longitudinal work is needed to examine age‐related change in both older autistic and autistic trait populations. Lay Summary: Little is known about the cognitive profile of middle‐aged and older autistic or high autistic trait adults. Using data from the PROTECT cohort and a well‐validated online cognitive assessment platform, the findings from the current study suggest that higher autistic traits are associated with worse cognitive functioning throughout later adulthood. This suggests that older adults with high autistic traits may require additional support as they age. [ABSTRACT FROM AUTHOR]

Introduction: Despite the association of vitamin D deficiency with incident dementia, the role of supplementation is unclear. We prospectively explored associations between vitamin D supplementation and incident dementia in 12,388 dementia‐free persons from the National Alzheimer's Coordinating Center. Methods: Baseline exposure to vitamin D was considered D+; no exposure prior to dementia onset was considered D−. Kaplan–Meier curves compared dementia‐free survival between groups. Cox models assessed dementia incidence rates across groups, adjusted for age, sex, education, race, cognitive diagnosis, depression, and apolipoprotein E (APOE) ε4. Sensitivity analyses examined incidence rates for each vitamin D formulation. Potential interactions between exposure and model covariates were explored. Results: Across all formulations, vitamin D exposure was associated with significantly longer dementia‐free survival and lower dementia incidence rate than no exposure (hazard ratio = 0.60, 95% confidence interval: 0.55–0.65). The effect of vitamin D on incidence rate differed significantly across the strata of sex, cognitive status, and APOE ε4 status. Discussion: Vitamin D may be a potential agent for dementia prevention. Highlights: In a prospective cohort study, we assessed effects of Vitamin D on dementia incidence in 12,388 participants from the National Alzheimer's Coordinating Center dataset.Vitamin D exposure was associated with 40% lower dementia incidence versus no exposure.Vitamin D effects were significantly greater in females versus males and in normal cognition versus mild cognitive impairment.Vitamin D effects were significantly greater in apolipoprotein E ε4 non‐carriers versus carriers.Vitamin D has potential for dementia prevention, especially in the high‐risk strata. [ABSTRACT FROM AUTHOR]

Apathy is one of the most common neuropsychiatric symptoms (NPS) and is associated with poor clinical outcomes. Research that helps define the apathy phenotype is urgently needed, particularly for clinical and biomarker studies. We used latent class analysis (LCA) with two independent cohorts to understand how apathy and depression symptoms co‐occur statistically. We further explored the relationship between latent class membership, demographics, and the presence of other NPS. The LCA identified a four‐class solution (no symptoms, apathy, depression, and combined apathy/depression), reproducible over both cohorts, providing robust support for an apathy syndrome distinct from depression and confirming that an apathy/depression syndrome exists, supported by the model fit test with the four‐class solution scores evidencing better fitting (Bayesian information criterion adjusted and entropy R2). Using a data‐driven method, we show distinct and statistically meaningful co‐occurrence of apathy and depressive symptoms. There was evidence that these classes have different clinical associations, which may help inform diagnostic categories for research studies and clinical practice. Highlights: We found four classes: no symptoms, apathy, depression and apathy/depression.Apathy conferred a higher probability for agitation.Apathy diagnostic criteria should include accompanying neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Background: Mood disorders are characterised by pronounced symptom heterogeneity, which presents a substantial challenge both to clinical practice and research. Identification of subgroups of individuals with homogeneous symptom profiles that cut across current diagnostic categories could provide insights in to the transdiagnostic relevance of individual symptoms, which current categorical diagnostic systems cannot impart.Aims: To identify groups of people with homogeneous clinical characteristics, using symptoms of manic and/or irritable mood, and explore differences between groups in diagnoses, functional outcomes and genetic liability.Method: We used latent class analysis on eight binary self-reported symptoms of manic and irritable mood in the UK Biobank and PROTECT studies, to investigate how individuals formed latent subgroups. We tested associations between the latent classes and diagnoses of psychiatric disorders, sociodemographic characteristics and polygenic risk scores.Results: Five latent classes were derived in UK Biobank (N = 42 183) and were replicated in the independent PROTECT cohort (N = 4445), including 'minimally affected', 'inactive restless', active restless', 'focused creative' and 'extensively affected' individuals. These classes differed in disorder risk, polygenic risk score and functional outcomes. One class that experienced disruptive episodes of mostly irritable mood largely comprised cases of depression/anxiety, and a class of individuals with increased confidence/creativity reported comparatively lower disruptiveness and functional impairment.Conclusions: Findings suggest that data-driven investigations of psychopathological symptoms that include sub-diagnostic threshold conditions can complement research of clinical diagnoses. Improved classification systems of psychopathology could investigate a weighted approach to symptoms, toward a more dimensional classification of mood disorders. [ABSTRACT FROM AUTHOR]

Alcohol misuse is known to be a risk factor for dementia. This study aimed to explore the association between risky drinking and cognitive impairment in a cohort study of middle aged and older people at risk of dementia. The sample comprised 15,582 people aged 50 and over drawn from the PROTECT study. Risky drinking was defined according to a score of 4 or above on the Alcohol Use Disorders Identification Test (AUDIT). Cognitive function was assessed on visual episodic memory, spatial working memory, verbal working memory and verbal reasoning. Risky drinkers at baseline were more likely to be younger, male, white British, married, of higher educational status, current or past tobacco smokers and to have moderate to severe depression than non-risky drinkers. Risky drinkers were also more likely to be impaired on self-reported instrumental activities of daily living and subjective cognitive decline. At baseline, risky drinkers were less likely than non-risky drinkers to show impairment on verbal reasoning and spatial working memory but not on visual episodic memory or verbal working memory. Risky drinking at baseline predicted decline in cognitive function on visual episodic memory, verbal reasoning and spatial working memory at 2 year follow-up, but only verbal working memory and spatial working memory remained significant outcomes after controlling for possible confounders. Although of small effect size, the association between risky drinking and impairment on measures of working memory and visuospatial function warrants further examination; particularly given the possibility of partial reversibility in alcohol related cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: In the absence of clear disease‐modifying drugs for dementia, modifiable risk factors have been explored to slow disease progression. Vitamin D deficiency is a risk factor, associated with higher risk of dementia. However, the role of vitamin D supplementation has been a subject of debate. Here we explored longitudinal associations between vitamin D supplementation and incident dementia in dementia‐free older adults from the National Alzheimer's Coordinating Center (NACC). Method: All participants had normal cognition (NC) or mild cognitive impairment (MCI) at baseline. Exposure to vitamin D supplementation was based on the NACC A4 medication form. Three vitamin D formulations were considered: calcium‐vitamin D, cholecalciferol, and ergocalciferol. For the primary analysis, participants with baseline exposure to any supplement were considered D+, while those without any exposure in advance of dementia diagnosis were considered D‐. Kaplan‐Meier curves were generated to compare ten‐year dementia‐free survival between D+ and D‐ groups. Cox proportional hazards models were implemented to assess the risk of dementia across vitamin D exposure groups, adjusted for baseline age, sex, years of education, race, APOE‐e4 status, cognitive diagnosis, and depression. To distinguish the associations of various vitamin D formulations with risk of dementia, sensitivity analyses were conducted to independently examine the effect of each formulation (calcium‐vitamin D, cholecalciferol, ergocalciferol). Result: The final sample consisted of 2836 D+ (mean age = 72.1; 68.4% female) and 5075 D‐ participants (mean age = 72; 45.1% female). MCI was more prevalent in D‐ vs D+ participants (35.7% vs 26.8%; p<0.001). Similarly, depression was more prevalent in D‐ vs D+ participants (6.9% vs. 4.3%, p<0.001). Across all three vitamin D formulations, exposure was associated with longer dementia‐free survival (p<0.001) and lower adjusted hazard ratio (HR) for incident dementia compared to no exposure (calcium‐vitamin D: HR = 0.56, 95%CI: 0.47‐0.67, p<0.001; cholecalciferol: HR = 0.72, 95%CI: 0.56‐0.91, p = 0.007; ergocalciferol: HR = 0.75, 95%CI: 0.63‐0.89, p<0.001) Conclusion: Our findings demonstrate that while adjusting for demographic, cognitive, behavioral, and genetic factors, exposure to vitamin D supplementation (calcium‐vitamin D, cholecalciferol, or ergocalciferol) in dementia‐free older adults was associated with lower risk of dementia, implicating vitamin D as a potential agent for dementia prevention. [ABSTRACT FROM AUTHOR]

A major concern with COVID‐19 was the impact it would have on individual health, the routine use of healthcare services, and physical activities, especially for older adults with comorbidities. To address this, we studied the association between these variables for older adults during the pandemic. To explore what policy instruments might be effective in mitigating the negative impacts, we investigated the effects of a shielding notice for those identified as vulnerable by the government and social media given it has been an important source for disseminating information of COVID‐19. We employed a UK sample with 3,807 participants aged ≥50 from an online survey administered during May and June 2020. Based on numbers of comorbidities, we separated the sample into a higher comorbidity group with those in the upper quartile of the sample (n = 829) and a lower comorbidity group with the remainder (n = 2,978). Statistical methods include chi‐squared analyses and cross‐sectional regressions. We found that individuals with higher comorbidities were more likely to have poorer self‐reported health and mental health and to receive a shielding notice from the government compared to those without (p < 0.05). Decreases in physical activities were associated with poorer self‐reported health and the increases were associated with better self‐reported health; on the other hand, the decreases were associated with poorer mental health, but the increases did not link to better mental health. Examination of the effects of policy instruments shows that a shielding notice was positively associated with primary care use. The notice generated greater reliance on telephone/video consultations compared to in‐person consultations, but the impacts were less strong for people with higher comorbidities. Frequent use of social media raised the probability of increasing physical activities and reduced that of decreasing physical activities, implying social media being an effective tool in promoting physical activities during the lockdown and subsequent restrictions. [ABSTRACT FROM AUTHOR]

Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials. [ABSTRACT FROM AUTHOR]

Background: While the gender/sex differences in neuropsychiatric symptoms in dementia population are well described, gender/sex differences in mild behavioral impairment (MBI) in dementia-free populations and the relationship to cognitive performance and to subsequent cognitive decline have not been studied.Objective: We aimed to explore gender/sex differences in the association of MBI with the level of cognitive performance and its rate of decline in a dementia-free cohort.Methods: We studied 8,181 older adults enrolled in the online PROTECT UK Study. MBI was assessed using the MBI Checklist and cognition was measured by digit span, paired associate learning, spatial working memory, and verbal reasoning. Statistical analysis was conducted using linear regression models and linear mixed-effects models.Results: Out of 8,181 individuals (median age 63 years, 73% females), 11% of females and 14% of males had MBI syndrome. Females exhibited less often symptoms of decreased motivation (45% versus 36% in males), impulse dyscontrol (40% versus 44% in males; p = 0.001) and social inappropriateness (12% versus 15%; p < 0.001), while they showed more often symptoms of emotional dysregulation (45% versus 36%; p < 0.001). The associations of MBI domains with some measures of cognitive performance and decline were stronger in males than females, with the exception of the association of emotional dysregulation with the rate of cognitive decline in verbal reasoning, which was present exclusively in females.Conclusion: MBI may influence cognition to a greater extent in males than in females. We propose that predictors and biomarkers of dementia should consider gender/sex as an effect modifier. [ABSTRACT FROM AUTHOR]

Objectives: Research with younger adults has begun to explore associations between autism/autistic traits and vulnerability to Post Traumatic Stress Disorder (PTSD). Large scale studies and/or examination of age‐effects have not been conducted. Methods: Adults aged 50 years+ from the PROTECT study (n = 20,220) completed items about current and childhood socio‐communicative difficulties characteristic of autism. Approximately 1% (n = 251) endorsed high autistic traits, henceforth the Autism Spectrum Traits (AST) group. Differences between the AST and an age—and sex‐matched "Comparison Older Adults" (COA; n = 9179) group were explored for lifetime traumatic experiences and current symptoms of PTSD, depression, and anxiety. Results: Almost 30% of the AST group, compared to less than 8% of the COA, reported severe trauma in childhood/adulthood, including emotional, physical or sexual abuse. Elevated current PTSD symptoms were reported by AST compared to COA. An interaction was observed between autistic traits and trauma severity; the effect of level of trauma on PTSD symptoms was significantly greater for AST versus COA participants. This interaction remained significant when controlling for current depression and anxiety symptoms. Conclusions: The findings suggest that high autistic traits may increase the likelihood of experiencing trauma across the lifespan, and the impact of severe trauma on PTSD symptoms. Older adults with high (vs. low) autistic traits may be at greater risk of experiencing PTSD symptoms in latter life. Future research should test whether the pattern of results is similar for diagnosed autistic adults. Key points: Using data from PROTECT, a large healthy ageing cohort, approximately 30% of middle‐aged and older adults with high autistic traits reported severe trauma in childhood/adulthood compared to less than 8% of a low autistic trait comparison groupMiddle‐aged and older adults with high autistic traits also reported elevated current PTSD symptoms when compared to the low autistic trait comparison groupAn interaction was observed between autistic traits and trauma severity; the effect of level of trauma on PTSD symptoms was significantly greater for those with high autistic traits vs. low autistic traitsMiddle‐aged and older adults with high autistic traits—especially those who have experienced severe trauma ‐ may need additional support to mitigate this vulnerability to poor mental health later in life [ABSTRACT FROM AUTHOR]

Objectives The mental and physical health profile of autistic people has been studied in adolescence and adulthood, with elevated rates of most conditions being reported. However, this has been little studied taking a dimensional approach to autistic traits and in older age. Methods A total of 20,220 adults aged 50–81 years from the PROTECT study reported whether they experienced persistent sociocommunicative traits characteristic of autism. Approximately 1%, 276 individuals, were identified as endorsing elevated autistic traits in childhood and currently, henceforth the "Autism Spectrum Trait" (AST) group. An age- and gender-matched comparison group was formed of 10,495 individuals who did not endorse any autistic behavioral traits, henceforth the "Control Older Adults" (COA) group. Differences between AST and COA groups were explored in self-reported psychiatric diagnoses, self-reported symptoms of current depression and anxiety, and self-reported physical health diagnoses. Associations were also examined between autistic traits and health across the whole sample. Results The AST group reported significantly elevated rates of psychiatric diagnoses compared to the COA group. Additionally, the AST group showed significantly higher self-reported symptoms of current depression and anxiety than the COA group. However, few differences were observed in individual physical health conditions, and no differences in total co-occurring physical diagnoses between groups. Similar associations between autistic traits and health were also found taking a dimensional approach across the whole sample. Discussion These findings suggest that older adults with elevated autistic traits may be at greater risk of poorer mental, but not physical, health in later life. Future studies should incorporate polygenic scores to elucidate the possible genetic links between the propensity to autism/high autistic traits and to psychiatric conditions, and to explore whether those with elevated autistic traits experience particular barriers to mental health care. [ABSTRACT FROM AUTHOR]

Agitation is common and problematic in care home residents with dementia. This study investigated the (cost)effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation in this population. Pragmatic, cluster randomised controlled trial with cost-effectiveness analysis in 50 care homes, follow-up at 6 and 16 months and stratified randomisation to intervention (n = 31) and control (n = 19). Residents with dementia were recruited at baseline (n = 726) and 16 months (n = 261). Clusters were not blinded to allocation. Three DCM cycles were scheduled, delivered by two trained staff per home. Cycle one was supported by an external DCM expert. Agitation (Cohen-Mansfield Agitation Inventory (CMAI)) at 16 months was the primary outcome. DCM was not superior to control on any outcomes (cross-sectional sample n = 675: 287 control, 388 intervention). The adjusted mean CMAI score difference was –2.11 points (95% CI –4.66 to 0.44, p = 0.104, adjusted ICC control = 0, intervention 0.001). Sensitivity analyses supported the primary analysis. Incremental cost per unit improvement in CMAI and QALYs (intervention vs control) on closed-cohort baseline recruited sample (n = 726, 418 intervention, 308 control) was £289 and £60,627 respectively. Loss to follow-up at 16 months in the original cohort was 312/726 (43·0%) mainly (87·2%) due to deaths. Intervention dose was low with only a quarter of homes completing more than one DCM cycle. No benefits of DCM were evidenced. Low intervention dose indicates standard care homes may be insufficiently resourced to implement DCM. Alternative models of implementation, or other approaches to reducing agitation should be considered. [ABSTRACT FROM AUTHOR]

Objective: Loneliness and physical activity are important targets for research into the impact of COVID-19 because they have established links with mental health, could be exacerbated by social distancing policies, and are potentially modifiable. In this study, we aimed to identify whether loneliness and physical activity were associated with worse mental health during a period of mandatory social distancing in the UK.Design: Population-based observational cohort study.Setting: Mental health data collected online during COVID-19 from an existing sample of adults aged 50 and over taking part in a longitudinal study of aging. All had comparable annual data collected between 2015 and 2019.Participants: Three-thousand two-hundred and eighty-one participants aged 50 and over.Measurements: Trajectories of depression (measured by PHQ-9) and anxiety (measured by GAD-7) between 2015 and 2020 were analyzed with respect to loneliness, physical activity levels, and a number of socioeconomic and demographic characteristics using zero-inflated negative binomial regression.Results: In 2020, PHQ-9 score for loneliness, adjusted for covariates, was 3.23 (95% CI: 3.01-3.44), an increase of around 1 point on all previous years in this group and 2 points higher than people not rated lonely, whose score did not change in 2020 (1.22, 95% CI: 1.12-1.32). PHQ-9 was 2.60 (95% CI: 2.43-2.78) in people with decreased physical activity, an increase of .5 on previous years. In contrast, PHQ-9 in 2020 for people whose physical activity had not decreased was 1.66, 95% CI: 1.56-1.75, similar to previous years. A similar relationship was observed for GAD-7 though the absolute burden of symptoms lower.Conclusion: After accounting for pre-COVID-19 trends, we show that experiencing loneliness and decreased physical activity are risk factors for worsening mental health during the pandemic. Our findings highlight the need to examine policies which target these potentially modifiable risk factors. [ABSTRACT FROM AUTHOR]

Background: The neuropsychiatric syndrome mild behavioral impairment (MBI) describes an at-risk state for dementia and may be a useful screening tool for sample enrichment.We hypothesized that stratifying a cognitively normal sample onMBI status would enhance the association between genetic risk for Alzheimer’s disease (AD) and cognition. Methods: Data from 4458 participants over age 50 without dementia was analyzed. A cognitive composite score was constructed and the MBI Checklist was used to stratify those with MBI and those without. Polygenic scores for AD were generated using summary statistics from the IGAP study. Results: AD genetic risk was associated with worse cognition in the MBI group but not in the no MBI group (MBI: β = –0.09, 95% confidence interval: –0.13 to –0.03, P = 0.002, R² = 0.003). The strongest association was in those with more severe MBI aged ≥65. Conclusions: MBI is an important feature of aging; screening on MBI may be a useful sample enrichment strategy for clinical research. [ABSTRACT FROM AUTHOR]