Neuropsychiatric symptoms are common in subjects with MCI and associated with higher risk of progression to AD. The cognitive and neuroanatomical correlates of neuropsychiatric symptoms in MCI have not been fully elucidated. In this study, we sought to evaluate the association between neuropsychiatric symptoms, cognitive function, regional tau deposition, and brain volumes in MCI subjects.

A total of 233 MCI and 305 healthy comparisons were selected from the ADNI-3 cohort. All the subjects underwent a comprehensive neuropsychological assessment, volumetric MR brain scan, and Flortaucipir PET for in vivo assessment of regional tau deposition. Prevalence of neuropsychiatric symptoms was evaluated by means of the NPI questionnaire. Multivariate analyses of variance were used to detect differences in cognitive and imaging markers in MCI subjects with and without neuropsychiatric symptoms.

61.4% MCI subjects showed at least one neuropsychiatric symptom, with the most prevalent ones being depression (26.1%), irritability (23.6%), and sleep disturbances (23.6%). There was a significant effect of neuropsychiatric symptoms on cognitive tests of frontal and executive functions. MCI subjects with neuropsychiatric symptoms showed reduced brain volumes in the orbitofrontal and posterior cingulate cortices, while no effects were detected on regional tau deposition. Posterior cingulate cortex volume was the only predictor of global neuropsychiatric burden in this MCI population.

Neuropsychiatric symptoms occur early in the AD trajectory and are mainly related to defects of control executive abilities and to the reduction of gray matter volume in the orbitofrontal and posterior cingulate cortices. A better understanding of the cognitive and neuroanatomical mechanisms of neuropsychiatric symptoms in MCI could help develop more targeted and efficacious treatment alternatives.

To examine the association between sleep duration in different stages of life and amnestic mild cognitive impairment (aMCI).

A total of 2472 healthy elderly and 505 patients with aMCI in China were included in this study. The study analyzed the association between aMCI and sleep duration in different stages of life.

We compared sleep duration in different stages of life and analyzed the association between Montreal Cognitive Assessment scores and sleep duration by curve estimation. Logistic regression was used to evaluate the association between aMCI and sleep duration.

In the analysis, there were no results proving that sleep duration in youth (P = 0.719, sleep duration < 10 hours; P = 0.999, sleep duration ≥ 10 hours) or midlife (P = 0.898, sleep duration < 9 hours; P = 0.504, sleep duration ≥ 9 hours) had a significant association with aMCI. In the group sleeping less than 7 hours in late life, each hour more of sleep duration was associated with approximately 0.80 of the original risk of aMCI (P = 0.011, odds ratio = 0.80, 95% confidence interval = 0.68–0.95).

Among the elderly sleeping less than 7 hours, there is a decreased risk of aMCI for every additional hour of sleep.

Frailty and late-life depression (LLD) often coexist and share several structural brain changes. We aimed to study the joint effect LLD and frailty have on brain structure.

Cross-sectional study

Academic Health Center

Thirty-one participants (14 LLD+Frail and 17 Never-depressed+Robust)

LLD was diagnosed by a geriatric psychiatrist according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition for single episode or recurrent major depressive disorder without psychotic features. Frailty was assessed using the FRAIL scale (0–5), classifying subjects as robust (0), prefrail (1–2), and frail (3–5). Participants underwent T1-weighted magnetic resonance imaging in which covariance analysis of subcortical volumes and vertex-wise analysis of cortical thickness values were performed to access changes in grey matter. Participants also underwent diffusion tensor imaging in which tract-based spatial statistics was used with voxel-wise statistical analysis on fractional anisotropy and mean diffusion values to assess changes in white matter (WM).

We found a significant difference in mean diffusion values (48,225 voxels; peak voxel: pFWER=0.005, MINI coord. (X,Y,Z) = −26,−11,27) between the LLD-Frail group and comparison group. The corresponding effect size (f=0.808) was large.

We showed the LLD+Frailty group is associated with significant microstructural changes within WM tracts compared to Never-depressed+Robust individuals. Our findings indicate the possibility of a heightened neuroinflammatory burden as a potential mechanism underlying the co-occurrence of both conditions and the possibility of a depression–frailty phenotype in older adults.

Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later.

We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale–Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later.

Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen’s d ≤ −0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit β = −0.8, 95% confidence interval: −1.6, −0.1, p = 0.03) independent of self-reported activity restriction and other key factors.

These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).

Apathy is a common symptom in mild cognitive impairment (MCI) and may predict progression to dementia. Little research, however, has investigated the longitudinal trajectory of apathy in patients with MCI or controlled for depression, which can mimic apathy, when examining its clinical correlates. The current study sought to address these issues.

A prospective longitudinal study was conducted over 3 years.

Nine memory clinics around Australia

One hundred and eighty-five patients with MCI at baseline.

Measures of cognition, function, neuropsychiatric symptoms, caregiver burden, and medication use were completed annually with additional assessments at 3 and 6 months. Patients were also assessed for dementia by expert clinicians at these time points.

Of 164 patients who completed measures of neuropsychiatric symptoms, 59 (36.0%) had apathy and 61 (37.2%) had depression. The proportion affected by apathy and overall apathy scores increased over time, in contrast to measures of depression, which remained relatively stable. Apathy was associated with incident dementia and worse cognition, function, neuropsychiatric symptoms, and caregiver burden independent of both depression and incident dementia. Depression was associated with worse function, albeit to lesser degree than apathy, and neuropsychiatric symptoms.

Apathy increases in MCI and is associated with worse clinical outcomes. These findings provide further evidence for apathy as a marker of clinical decline in older people and poorer outcomes across neurocognitive disorders.

At the end of this workshop, participants will be able to:

1. - Integrate a human rights and dignity-based strategies into daily clinical care for older persons with mental health conditions

2. - Identify the effects of intersections of ageism, ableism, mentalism and elder abuse on the care provided to older persons with mental health conditions

3. - Describe and support the need for an international (UN) Convention on the rights of older persons to improve the care of older persons with mental health conditions

Our world faces rapid population aging. Based on the WHO estimates, nearly 20% of older persons will have mental health conditions such as dementia, depression, anxiety and substance use, often complicated by physical and psychosocial comorbidities. Various mental health inequalities exist in this vulnerable population negatively influencing their healthcare and social status. This includes the ‘triple jeopardy’ of ageism, ableism and mentalism. The ongoing COVID-19 crisis has only widened the marginalization of older persons and especially those with mental health conditions.

Even though there has been a paradigm-shift in neurobiological understanding of psychogeriatrics, dignity-based mental healthcare is still silent in research as well as practice. This workshop brings in recommendations to include the principles of rights, dignity, equality, equity and respect in clinical care for older persons living with mental health conditions, including dementia. These suggestions are based on literature review, position statements of global organizations working in this area, the Decade enablers of the UN Decade of Healthy Aging (2021-2030) and also clinical experience of the authors. Special focus will be on end-of-life care, advance directives and those in institutionalized settings.

The workshop will involve a strategic and interactive discussion based on real-life case vignettes. Feedback will be sought on the perceived status of dignity and human rights in current clinical practice. Focus will be on ensuring dignity and promoting human rights in routine clinical care and patient-physician communication, age-friendly healthcare settings for older persons and the role of dignity therapy. The need for an International Convention for the rights of older persons will also be highlighted with evidence.

Elder abuse and inadequate end-of-life care as two of the many common manifestations of the implicit bias and core root cause of the phenomenon of the “ageism spectrum”. Ensuring dignity and human rights in older persons can combat ageism and prevent elder abuse. Adequate sensitivity and training of professionals in this area will set the future pathway for dignified mental health interventions in the older persons with mental health conditions that are devoid of age-based discrimination and prejudice.

To characterize the features of aged care users who died by suicide and examine the use of mental health services and psychopharmacotherapy in the year before death.

Population-based, retrospective exploratory study

Individuals who died while accessing or waiting for permanent residential aged care (PRAC) or home care packages in Australia between 2008 and 2017.

Linked datasets describing aged care use, date and cause of death, health care use, medication use, and state-based hospital data collections.

Of 532,507 people who died, 354 (0.07%) died by suicide, including 81 receiving a home care package (0.17% of all home care package deaths), 129 in PRAC (0.03% of all deaths in PRAC), and 144 approved for but awaiting care (0.23% of all deaths while awaiting care). Factors associated with death by suicide compared to death by another cause were male sex, having a mental health condition, not having dementia, less frailty, and a hospitalization for self-injury in the year before death. Among those who were awaiting care, being born outside Australia, living alone, and not having a carer were associated with death by suicide. Those who died by suicide more often accessed Government-subsidized mental health services in the year before their death than those who died by another cause.

Older men, those with diagnosed mental health conditions, those living alone and without an informal carer, and those hospitalized for self-injury are key targets for suicide prevention efforts.

People with dementia can face barriers when trying to access care after a diagnosis, particularly in young-onset dementia (YOD). Little is known about the effects of ethnicity on the use of anti-dementia medication and variations between age groups. The aim of this study was to analyze national data on variations in the uptake of anti-dementia medication between people with YOD and late-onset dementia (LOD).

Cross-sectional longitudinal cohort study.

Data from the U.S. National Alzheimer’s Coordinating Centre were obtained from September 2005 to March 2019.

First visits of people with a diagnosis of Alzheimer’s disease (AD) dementia, Lewy body dementia (LBD), and Parkinson’s disease dementia (PDD) were included.

Logistic regression was used to analyze the effects of education and ethnicity on use of cholinesterase inhibitors and memantine, accounting for YOD/LOD, gender, living situation, severity stage, and comorbidities.

In total, 15,742 people with AD dementia and LBD/PDD were included, with 11,019 PwD having completed a first follow-up visit. Significantly more people with YOD used memantine than those with LOD, while fewer used cholinesterase inhibitors. PwD from minority ethnic backgrounds used memantine and cholinesterase inhibitors less often than those from a White ethnic background. Logistic regression analysis showed that ethnicity was a significant determinant of both memantine and cholinesterase inhibitors usage, while education was only a significant determinant for memantine usage.

Findings highlight the impact of social factors on current usage of anti-dementia medication and the need for more resources to enable equitable use of anti-dementia medication.

This study examines whether transition to caregiving within or outside the household is associated with changes in suicidal ideation and whether this depends on the type of caregiver relationship, the age or gender of the caregiver, or the welfare system.

Longitudinal study.

Ten European countries.

Data from the Survey of Health, Ageing, and Retirement in Europe were used (waves 1, 2, 4, 5, and 6) including participants aged ≥40 years (pooled Observations = 171,848).

Suicidal ideation was measured using the Euro-D scale. Caregiving was measured as care inside and outside the household, and for different recipients. Fixed effects logistic regression analyses, adjusted for health and sociodemographic factors, were used.

Transitioning into caregiving inside the household was associated with higher odds of suicidal ideation, in particular if they transitioned into care for partners or parents and within Southern and Bismarckian welfare systems. Transitioning into caregiving outside the household was not associated with suicidal ideation, except among those transitioning into caregiving for non-relatives (higher odds of suicidal ideation), and among male and older caregivers (lower odds of suicidal ideation). Suicide ideation was higher among caregivers in Southern compared to Bismarckian or Scandinavian welfare systems.

Informal caregiving is associated with suicidal ideation among caregivers inside but not among all caregivers outside the household. The caregiver’s characteristics, the care relationship, and the welfare system play an important role. Preventing suicidal ideation requires interventions that focus on informal caregivers and consider their individual and contextual factors.

There is an urgent need for clinical blood biomarkers which can rule in/out neurological disorders early in those with psychiatric symptoms, personality or behavioural changes and/or functional decline together with cognitive symptoms. The neuronal axonal protein neurofilament light (NfL) is released from damaged neuronal axons and can be measured in in blood and cerebrospinal fluid (CSF). We have undertaken a series of studies aimed at examining the clinical utility of blood and CSF NfL in assisting with the distinction between psychiatric and neurodegenerative / neurological disorders.

Since 2016 we have measured blood and CSF NfL levels across multiple psychiatric and neurological populations recruited through Neuropsychiatry, Royal Melbourne Hospital and our collaborators (national and international). We have described our findings in a series of published studies. Data from our ongoing work, in larger cohorts and diagnostic groups, will be presented. The diagnostic groups include people with psychiatric disorders (schizophrenia, bipolar disorder, depression, functional neurological disorders), neurodegenerative disorders (Alzheimer’s disease, frontotemporal dementia, Huntington’s disease, Niemann-Pick Type C) and neurological disorders (e.g., epilepsy).

Our initial pilot study (n=129) found that CSF NfL was a promising biomarker in differentiating psychiatric from neurological disorders. In our larger follow up larger study (n=498) which included more diagnostic groups CSF NfL levels exhibited high accuracy (91%), sensitivity (92%), and specificity (87%) in differentiating psychiatric from neurological disorders, and distinguished behavioural variant frontotemporal dementia from frontal lobe syndrome phenocopies/mimics, with high accuracy. We have found that NfL is not elevated in people with treatment resistant schizophrenia compared to controls and is elevated in people with Niemann-Pick Type C compared to people with psychiatric disorders and controls. Further (unpublished) data has shown that these findings are replicated with plasma NfL levels across 400 further psychiatric, neurological and control participants.

NfL is a highly promising biomarker which differentiates psychiatric from neurological disorders with high sensitivity and specificity. The translation of NfL levels into standard clinical practice could substantially improve the clinical diagnostic process in people with complex neuropsychiatric and cognitive disorders.

Dementia assessment includes cognitive and behavioral testing with informant verification. Conventional testing is resource-intensive, with uneven access. Online unsupervised assessments could reduce barriers to risk assessment. The aim of this study was to assess the relationship between informant-rated behavioral changes and participant-completed neuropsychological test performance in older adults, both measured remotely via an online unsupervised platform, the Brain Health Registry (BHR).

Observational cohort study.

Community-dwelling older adults participating in the online BHR. Informant reports were obtained using the BHR Study Partner Portal.

The final sample included 499 participant–informant dyads.

Participants completed online unsupervised neuropsychological assessment including Forward Memory Span, Reverse Memory Span, Trail Making B, and Go/No-Go tests. Informants completed the Mild Behavioral Impairment Checklist (MBI-C) via the BHR Study Partner portal. Cognitive performance was evaluated in MBI+/− individuals, as was the association between cognitive scores and MBI symptom severity.

Mean age of the 499 participants was 67, of which 308/499 were females (61%). MBI + status was associated with significantly lower memory and executive function test scores, measured using Forward and Reverse Memory Span, Trail Making Errors and Trail Making Speed. Further, significant associations were found between poorer objectively measured cognitive performance, in the domains of memory and executive function, and MBI symptom severity.

These findings support the feasibility of remote, informant-reported behavioral assessment utilizing the MBI-C, supporting its validity by demonstrating a relationship to online unsupervised neuropsychological test performance, using a previously validated platform capable of assessing early dementia risk markers.

Among people with dementia, poor nutritional status has been associated with worse cognitive and functional decline, but few studies have examined its association with neuropsychiatric symptoms (NPS). We examined this topic in a population-based sample of persons with dementia.

Longitudinal, observational cohort study.

Community.

Two hundred ninety-two persons with dementia (71.9% Alzheimer’s disease, 56.2% women) were followed up to 6 years.

We used a modified Mini-Nutritional Assessment (mMNA) and the Neuropsychiatric Inventory (NPI) to evaluate nutritional status and NPS, respectively. Individual linear mixed effects models examined the associations between time-varying mMNA total score or clinical categories (malnourishment, risk for malnourishment, or well-nourished) and NPI total score (excluding appetite domain) or NPI individual domain or cluster (e.g. psychosis) scores. Covariates tested were dementia onset age, type, and duration, medical comorbidities, sex, apolipoprotein E (APOE) genotype, and education.

Compared to the well-nourished, those at risk for malnourishment and those malnourished had higher total NPI scores [b (95% CI) = 1.76 (0.04, 3.48) or 3.20 (0.62, 5.78), respectively], controlling for significant covariates. Higher mMNA total score (better nutritional status) was associated with lower total NPI [b (95% CI) = −0.58 (−0.86, −0.29)] and lower domain scores for psychosis [b (95% CI) = −0.08 (−0.16, .004)], depression [b (95% CI = −0.11 (−0.16, −0.05], and apathy [b (95% CI = −0.19 (−0.28, −0.11)].

Worse nutritional status is associated with more severe NPS. Dietary or behavioral interventions to prevent malnutrition may be beneficial for persons with dementia.

Post-diagnosis young onset dementia (YOD) care is often fragmented, with services delivered across aged care, health care, and social care sectors. The aim of this project was to test the feasibility and effectiveness of a learning collaborative implementation strategy for improving the cross-sector integration of care for people with YOD.

We conducted a longitudinal mixed-methods process evaluation, and recruited one representative from three Australian aged care organisations, three disability care organisations, and three organisations contracted to deliver care navigation services. One representative from each organisation joined a learning collaborative within their local area and completed a six-module online education package incorporating written resources, webinars, collaboration, and expert mentoring. Participants identified gaps in services in their region and barriers to care integration, and developed a shared plan to implement change. Normalisation Process Theory was applied to understand acceptability, penetration, and sustainability of the implementation strategy, as well as barriers and enabling factors.

Dementia knowledge measured by the Dementia Knowledge and Awareness Scale was high among the professionals at the start of the implementation period (Mean = 39.67, standard deviation = 9.84) and did not change by the end (Mean=39.67, standard deviation = 8.23). Quantitative data demonstrated that clinicians dedicated on average half of the recommended time commitment to the project. However, qualitative data identified that the learning collaborative strategy enhanced commitment to implementing integrated care and promoted action toward integrating previously disparate care services. Participant commitment to the project was influenced by their sense of obligation to their team, and teams that established clear expectations and communication strategies early were able to collaborate and use the implementation plan more effectively (demonstrating collective action). Teams were less likely to engage in the collective action or reflexive monitoring required to improve care integration if they did not feel engaged with their learning collaborative.

Learning collaboratives hold promise as a strategy to improve cross-sector service collaboration for people with YOD and their families but must maximise group cohesion and shared commitment to change.

Awareness is the recognition of changes caused by deficits related to the dementia process. Awareness is related to a given object, like memory functioning or functional status. Objects of awareness can be grouped into a range of domains, including cognition, functional ability, emotional and social functioning, and behavioral difficulties. Preserved awareness in people with young onset dementia (YOD) has been reported; however, there is a lack of research investigating whether there are differences in the domains of awareness impairment according to the age at onset of dementia. This study compared the differences in awareness and its domains and examined associations with cognition, functionality, neuropsychiatric symptoms, social and emotional functioning, and quality of life (QoL) among people with YOD and late onset dementia (LOD).

A group of 136 people with dementia and their caregivers (YOD= 50 and LOD= 86) were consecutively selected. We assessed awareness of disease, dementia severity, cognition, functionality, neuropsychiatric symptoms, social and emotional functioning, and QoL.

People with YOD presented more neuropsychiatric symptoms and worse cognition and functional ability than those with LOD. Compared to people with LOD, there were higher levels of awareness total score, awareness of cognitive functioning and health condition, and awareness of functional activity impairments domains in people with YOD, even in the moderate stage of the disease. There were no significant differences between groups in the emotional state, and social functioning and relationships domains of awareness. Multivariate linear regressions showed that functionality had a broad relationship with awareness in people with YOD. In contrast, neuropsychiatric symptoms and QoL were more significant to the awareness of people with LOD.

Different clinical variables are associated with different domains in YOD and LOD groups, reinforcing the heterogeneity of awareness in dementia. Differences in awareness and its domains in YOD and LOD may be particularly relevant to enabling interventions focused on meeting their specific needs and those of their families.

This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.

A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.

Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).

Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer’s disease while considering the burden on the healthcare system.

Cognition and the ability to take care of daily activities and oneself gradually declines among people with dementia. Studies are scarce, especially regarding how people with young-onset dementia (YOD) (<65 years) experience the quality of their lives with the progression of dementia. People with dementia living alone face special challenges. The aim was to examine the experience of the quality of life with YOD as a single person.

The study presents a longitudinal case study with in-depth interviews exploring the experiences of a person with YOD. Individual interviews were conducted seven times over a period of three years from 2014 to 2017.

We examined if and how seven themes concerning the quality of life and well-being were fruitful for understanding the experiences of dementia in the everyday life of a single individual. The study explored needs and challenges during the development of dementia, and how the person reacted over time, set in context. The themes significant for well-being are: identity, connectedness, security, autonomy, meaning, growth and joy.

The study shows how treatment, support, and services must be individualized when dementia develops in order to support identity, resources and mastering capacity, and promote well-being.