Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Toward a theory-based specification of non-pharmacological treatments in aging and dementia: Focused reviews and methodological recommendations.

INTRODUCTION: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results. METHODS: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System. RESULTS: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols. DISCUSSION: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area.

Integrated care for adults with dementia and other cognitive disorders.

The importance of better care integration is emphasized in many national dementia plans. The inherent complexity of organizing care for people with dementia provides both the justification for improving care integration and the challenges to achieving it. The prevention, detection, and early diagnosis of cognitive disorders mainly resides in primary care, but how this is best integrated within the range of disorders that primary care clinicians are expected to screen is unclear. Models of integrated community dementia assessment and management have varying degrees of involvement of primary and specialist care, but share an emphasis on improving care coordination, interdisciplinary teamwork, and personalized care. Integrated care strategies in acute care are still in early development, but have been a focus of investigation in the past decade. Integrated care outreach strategies to reduce transfers from long-term residential care to acute care have been consistently effective. Integrated long-term residential care includes considerations of end-of-life care. Future directions should include strategies for training and education, early detection in anticipation of disease modifying treatments, integration of technological developments into dementia care, integration of dementia care into general health and social care, and the encouragement of a dementia-friendly society.

Understanding self-harm in older people: a systematic review of qualitative studies.

OBJECTIVE: Rates of suicide in older adults are generally higher than other age groups. Although risk factors for suicide attempts, and self-harm more generally, in this population are well-characterised, many of these vulnerabilities are common to older people and individual motivations are less well understood. Qualitative research may reveal more about the underlying thought processes, meaning and experiences of older people who self-harm. METHODS: A systematic review of qualitative studies examining the reasons why older people have self-harmed was undertaken by searching databases and screening the reference lists of articles. The quality of studies was critically appraised. A content analysis was performed to identify themes. RESULTS: The search yielded eight studies of variable quality which met the inclusion criteria; three pertained to indirect self-harm (refusal to eat or take medications and self-neglect) and five related to suicidal behaviour. Themes emerging from the analysis of studies of people who had self-neglected included control, impaired decision-making and coping skills and threats to self-identity and continuity. In those who had suicidal behaviour, themes related to loss of and regaining control; alienation, disconnectedness and invisibility; meaningless and raison d'etre; and accumulated suffering and a 'painful life'. CONCLUSIONS: There is scant literature evaluating self-harm in older people using qualitative methods. Nonetheless, this review suggests that active and passive self-harm should be considered as distinct entities as the underlying motivations and intents differ. Understanding individual perceptions and experiences which lead to self-harm may guide clinicians in delivering more sensitive, holistic interventions and counter ageism.

Non-pharmacological interventions for Lewy body dementia: a systematic review.

Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics. This combination of features presents challenges for pharmacological management. Given this, we sought to review evidence for non-pharmacological interventions with patients with Lewy body dementia and their carers. Bibliographic databases were searched using a wide range of search terms and no restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 21 studies including two randomised controlled trials with available subgroup data, seven case series, and 12 case studies. Most studies reported beneficial effects of the interventions used, though the only sizeable study was on dysphagia, showing a benefit of honey-thickened liquids. Given the heterogeneity of interventions and poor quality of the studies overall, no quantitative synthesis was possible. Overall, identified studies suggested possible benefits of non-pharmacological interventions in Lewy body dementia, but the small sample sizes and low quality of studies mean no definite recommendations can be offered. Our findings underscore the clear and urgent need for future research on this topic.

Rational Suicide, Euthanasia, and the Very Old: Two Case Reports.

Suicide amongst the very old is an important public health issue. Little is known about why older people may express a wish to die or request euthanasia and how such thoughts may intersect with suicide attempts. Palliative care models promote best care as holistic and relieving suffering without hastening death in severely ill patients; but what of those old people who are tired of living and may have chronic symptoms, disability, and reduced quality of life? Two cases of older people who attempted suicide but expressed a preference for euthanasia were it legal are presented in order to illustrate the complexity underlying such requests. The absence of a mood or anxiety disorder underpinning their wishes to die further emphasises the importance of understanding the individual's narrative and the role of a formulation in guiding broad biopsychosocial approaches to management.

The effects of humor therapy on nursing home residents measured using observational methods: the SMILE cluster randomized trial.

OBJECTIVES: To evaluate the effects of humor therapy assessed using observational methods on agitation, engagement, positive behaviors, affect, and contentment. DESIGN: Single-blind cluster randomized controlled trial. SETTING: A total of 35 Sydney nursing homes. PARTICIPANTS: All eligible residents within geographically defined areas within each nursing home were invited to participate. INTERVENTION: Professional "ElderClowns" provided 9 to 12 weekly humor therapy sessions, augmented by resident engagement by trained staff "LaughterBosses." Controls received usual care. MEASUREMENTS: The Behavior Engagement Affect Measure (BEAM) touchpad observational tool was used to capture real-time behavioral data. The tool assesses the duration in seconds of agitation, positive behavior toward others, engagement, and affect (angry, anxious, happy, neutral, sad). RESULTS: Seventeen nursing homes (189 residents) received the intervention and 18 homes (209 residents) received usual care. Over 26 weeks, in comparison with controls, the humor therapy group decreased in duration of high agitation (effect size = 0.168 and 0.129 at 13 and 26 weeks, respectively) and increased in duration of happiness (effect size = 0.4 and 0.236 at 13 and 26 weeks, respectively). CONCLUSION: We confirmed that humor therapy decreases agitation and also showed that it increases happiness. Researchers may consider evaluating impacts of nonpharmaceutical interventions on positive outcomes. Computer-assisted observational measures should be considered, particularly for residents with dementia and when the reliability of staff is uncertain.

Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts.

BACKGROUND: Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed. OBJECTIVE: To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment. METHODS: Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer's disease were excluded. A Mini-Mental State Examination score of <24 was used to define impaired cognitive function. RESULTS: Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60-7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance (AOR 1.74, 95% CI: 1.03-2.95, p = 0.04). CONCLUSIONS: High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority.

Successful ingredients in the SMILE study: resident, staff, and management factors influence the effects of humor therapy in residential aged care.

OBJECTIVE: To test the hypothesis that individual and institutional-level factors influence the effects of a humor therapy intervention on aged care residents. METHODS: Data were from the humor therapy group of the Sydney Multisite Intervention of LaughterBosses and ElderClowns, or SMILE, study, a single-blind cluster randomized controlled trial of humor therapy conducted over 12 weeks; assessments were performed at baseline, week 13, and week 26. One hundred eighty-nine individuals from 17 Sydney residential aged care facilities were randomly allocated to the humor therapy intervention. Professional performers called "ElderClowns" provided 9-12 weekly humor therapy 2-hour sessions, augmented by trained staff, called "LaughterBosses." Outcome measures were as follows: Cornell Scale for Depression in Dementia, Cohen-Mansfield Agitation Inventory, Neuropsychiatric Inventory, the withdrawal subscale of Multidimensional Observation Scale for Elderly Subjects, and proxy-rated quality of life in dementia population scale. Facility-level measures were as follows: support of the management for the intervention, commitment levels of LaughterBosses, Environmental Audit Tool scores, and facility level of care provided (high/low). Resident-level measures were engagement, functional ability, disease severity, and time-in-care. Multilevel path analyses simultaneously modeled resident engagement at the individual level (repeated measures) and the effects of management support and staff commitment to humor therapy at the cluster level. RESULTS: Models indicated flow-on effects, whereby management support had positive effects on LaughterBoss commitment, and LaughterBoss commitment increased resident engagement. Higher resident engagement was associated with reduced depression, agitation, and neuropsychiatric scores. CONCLUSION: Effectiveness of psychosocial programs in residential aged care can be enhanced by management support, staff commitment, and active resident engagement.

Increased risk of cognitive impairment in patients with diabetes is associated with metformin.

OBJECTIVE: To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes. RESEARCH DESIGN AND METHODS: Participants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n=480) or mild cognitive impairment (n=187) and those who were cognitively intact (n=687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n=104) or impaired glucose tolerance (n=22). RESULTS: Participants with diabetes (n=126) had worse cognitive performance than participants who did not have diabetes (n=1,228; adjusted odds ratio 1.51 [95% CI 1.03-2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19-0.92]). CONCLUSIONS: Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.

Desired characteristics and outcomes of community care services for persons with dementia: what is important according to clients, service providers and policy?

AIM: To examine views of Australian consumers, service providers and policy representatives on important characteristics and outcomes for community care. METHOD: Interviews, with 32 consumers (one person with dementia (PWD) and 31 carers), 32 service providers and four policy representatives, were analysed thematically. RESULTS: Outcomes important to consumers and service providers were that PWD can stay at home safely with personalised activities and socialisation; and that carers receive emotional support, respite and continue paid employment. Consumers and service providers said it was important that community care services were flexible and reliable and provided adequate hours of care and there was continuity of appropriate and well-trained staff. Overall responses of policy representatives were congruent with consumers and service providers but did not comprehensively cover the issues. CONCLUSIONS: Community care policies and service practices need to be re-examined to make sure that they are person-centred and reflect consumer needs, for instance by integrating client and carer services and providing appropriate activities for PWD.

The Sydney Multisite Intervention of LaughterBosses and ElderClowns (SMILE) study: cluster randomised trial of humour therapy in nursing homes.

OBJECTIVES: To determine whether humour therapy reduces depression (primary outcome), agitation and behavioural disturbances and improves social engagement and quality-of-life in nursing home residents. DESIGN: The Sydney Multisite Intervention of LaughterBosses and ElderClowns study was a single-blind cluster randomised controlled trial of humour therapy. SETTING: 35 Sydney nursing homes. PARTICIPANTS: All eligible residents within geographically defined areas within each nursing home were invited to participate. INTERVENTION: Professional 'ElderClowns' provided 9-12 weekly humour therapy sessions, augmented by resident engagement by trained staff 'LaughterBosses'. Controls received usual care. MEASUREMENTS: Depression scores on the Cornell Scale for Depression in Dementia, agitation scores on the Cohen-Mansfield Agitation Inventory, behavioural disturbance scores on the Neuropsychiatric Inventory, social engagement scores on the withdrawal subscale of Multidimensional Observation Scale for Elderly Subjects, and self-rated and proxy-rated quality-of-life scores on a health-related quality-of-life tool for dementia, the DEMQOL. All outcomes were measured at the participant level by researchers blind to group assignment. RANDOMISATION: Sites were stratified by size and level of care then assigned to group using a random number generator. RESULTS: Seventeen nursing homes (189 residents) received the intervention and 18 homes (209 residents) received usual care. Groups did not differ significantly over time on the primary outcome of depression, or on behavioural disturbances other than agitation, social engagement and quality of life. The secondary outcome of agitation was significantly reduced in the intervention group compared with controls over 26 weeks (time by group interaction adjusted for covariates: p=0.011). The mean difference in change from baseline to 26 weeks in Blom-transformed agitation scores after adjustment for covariates was 0.17 (95% CI 0.004 to 0.34, p=0.045). CONCLUSIONS: Humour therapy did not significantly reduce depression but significantly reduced agitation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry -ACTRN12611000462987.

Study protocol for a randomized controlled trial of humor therapy in residential care: the Sydney Multisite Intervention of LaughterBosses and ElderClowns (SMILE).

BACKGROUND: Humor therapy is a non-pharmacological intervention with potential to improve mood and quality of life for institutionalized older persons, including those with dementia. The primary aims of the Sydney Multisite Intervention of LaughterBosses and ElderClowns (SMILE) are to examine the effects of humor therapy on residents' mood, quality of life, social engagement, and agitation. METHODS: SMILE is a single-blinded cluster-randomized controlled trial where 398 consented residents in 35 residential aged care facilities will be allocated to receive humor therapy or usual care. Residents allocated to the intervention group will engage in humor therapy with professional performers (ElderClowns) and trained facility staff (LaughterBosses) for a minimum of nine two-hour sessions over 12 weeks as well as engaging humorously with LaughterBosses during the course of daily care. The usual care control group will not engage in any formal humor therapy. Researchers, blind to treatment allocation, will assess residents at baseline (week 0), post-intervention (week 13), and follow-up (week 26). The measurement suite includes the Cornell Scale for Depression in Dementia, the Dementia Quality of Life Scale, the Multidimensional Observation Scale for Elderly Subjects, the Cohen-Mansfield Agitation Inventory, and the Neuropsychiatric Inventory. Observations of residents' engagement will be recorded at each humor therapy session. CONCLUSIONS: SMILE is the first large rigorous study of humor therapy in aged care.

Nonpharmacological therapies in Alzheimer's disease: a systematic review of efficacy.

INTRODUCTION: Nonpharmacological therapies (NPTs) can improve the quality of life (QoL) of people with Alzheimer's disease (AD) and their carers. The objective of this study was to evaluate the best evidence on the effects of NPTs in AD and related disorders (ADRD) by performing a systematic review and meta-analysis of the entire field. METHODS: Existing reviews and major electronic databases were searched for randomized controlled trials (RCTs). The deadline for study inclusion was September 15, 2008. Intervention categories and outcome domains were predefined by consensus. Two researchers working together detected 1,313 candidate studies of which 179 RCTs belonging to 26 intervention categories were selected. Cognitive deterioration had to be documented in all participants, and degenerative etiology (indicating dementia) had to be present or presumed in at least 80% of the subjects. Evidence tables, meta-analysis and summaries of results were elaborated by the first author and reviewed by author subgroups. Methods for rating level of evidence and grading practice recommendations were adapted from the Oxford Center for Evidence-Based Medicine. RESULTS: Grade A treatment recommendation was achieved for institutionalization delay (multicomponent interventions for the caregiver, CG). Grade B recommendation was reached for the person with dementia (PWD) for: improvement in cognition (cognitive training, cognitive stimulation, multicomponent interventions for the PWD); activities of daily living (ADL) (ADL training, multicomponent interventions for the PWD); behavior (cognitive stimulation, multicomponent interventions for the PWD, behavioral interventions, professional CG training); mood (multicomponent interventions for the PWD); QoL (multicomponent interventions for PWD and CG) and restraint prevention (professional CG training); for the CG, grade B was also reached for: CG mood (CG education, CG support, multicomponent interventions for the CG); CG psychological well-being (cognitive stimulation, multicomponent interventions for the CG); CG QoL (multicomponent interventions for PWD and CG). CONCLUSION: NPTs emerge as a useful, versatile and potentially cost-effective approach to improve outcomes and QoL in ADRD for both the PWD and CG.

Dementia services in Australia.

AIM: To describe dementia services in Australia. METHOD: Limited review of current government policies and relevant papers. RESULTS: Australians with dementia, currently estimated at 220 000, are expected to number 1.13 million by 2050. In response, Commonwealth and State Australian governments have developed comprehensive plans and systems including expansion of community care services and packages, improvement in quality of residential care and initiatives to address behavioural and psychological symptoms of dementia. Alzheimer's Australia, which continues to be a powerful advocate for improvement in services, has pioneered a prevention programme to delay dementia onset. CONCLUSION: Further developments should aim to increase awareness, reduce stigma, enhance carer support improve timely diagnosis and support for special population groups, notably those from Indigenous and non-English speaking communities and those with younger onset dementia and correct relative underfunding for dementia research. Dementia care in Australia is well developed but gaps remain.

Management of agitation and aggression associated with Alzheimer disease.

Agitation and aggression are frequently occurring and distressing behavioral and psychological symptoms of dementia (BPSD). These symptoms are disturbing for individuals with Alzheimer disease, commonly confer risk to the patient and others, and present a major management challenge for clinicians. The most widely prescribed pharmacological treatments for these symptoms-atypical antipsychotics-have a modest but significant beneficial effect in the short-term treatment (over 6-12 weeks) of aggression but limited benefits in longer term therapy. Benefits are less well established for other symptoms of agitation. In addition, concerns are growing over the potential for serious adverse outcomes with these treatments, including stroke and death. A detailed consideration of other pharmacological and nonpharmacological approaches to agitation and aggression in patients with Alzheimer disease is, therefore, imperative. This article reviews the increasing evidence in support of psychological interventions or alternative therapies (such as aromatherapy) as a first-line management strategy for agitation, as well as the potential pharmacological alternatives to atypical antipsychotics-preliminary evidence for memantine, carbamazepine, and citalopram is encouraging.

Prediction of cognitive decline after stroke using proton magnetic resonance spectroscopy.

Structural MRI measures have been used to predict cognitive decline in elderly subjects, but few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) for this purpose, particularly after stroke. We studied the potential of (1)H-MRS to predict cognitive decline in patients with stroke or TIA and healthy ageing controls over 12 months and 3 years. Structural MRI and single-voxel (1)H-MRS in the frontal white matter and the occipito-parietal gray matter were performed at the index assessment (3-6 months post-stroke) in 49 stroke/TIA patients and 60 controls. Neuropsychological testing was performed at the index assessment and repeated at 12 months in 30 stroke/TIA patients and 49 controls, and at 3 years in 25 patients and 48 controls. In stroke/TIA patients, frontal NAA/Cr predicted cognitive decline over 12 months and 3 years, and in elderly control subjects frontal NAA predicted cognitive decline over 12 months only. In stroke/TIA patients, the (1)H-MRS measures were better predictors of cognitive decline than structural measures. (1)H-MRS may be useful in assessing early cognitive impairment after stroke/TIA and in normal ageing.

Tocopherol (vitamin E) in Alzheimer's disease and other neurodegenerative disorders.

In this article, we review the evidence that tocopherol (vitamin E) may have a role to play in the prevention and treatment of Alzheimer's disease and other neurological diseases. The theoretical rationale for the effectiveness of tocopherol as treatment and/or prevention of Alzheimer's disease is based on its antioxidant properties. Results from animal and in vitro studies provide evidence to support use of tocopherol for prevention and treatment of degenerative neurological diseases. Furthermore, several, but not all, epidemiological, cross-sectional, prospective studies indicate that tocopherol may have protective effects in Alzheimer's disease, although dietary and supplemental forms of the vitamin may differ in their efficacy. Mixed results have been obtained from clinical trials. Evidence of the use of tocopherol as a protective measure or as therapy in neurological diseases other than Alzheimer's disease is less compelling. To date, there are no clear-cut answers as to whether tocopherol is worth prescribing, but current clinical practice favours its use in the treatment of Alzheimer's disease.

Aggression in the elderly.

Aggression is a common behavioral symptom of dementia. Aggression is associated with frontotemporal dementia, greater dementia severity, cognitive decline, and other behavioral and psychological disturbances. It is influenced by the environment and has been correlated with neuropathologic changes and certain polymorphisms. Aggression in dementia patients results in higher psychotropic use and distress to family caregivers and nursing home staff; it is predictive of institutionalization. There is empirical evidence for the efficacy of pharmacotherapy and more limited evidence for psychosocial interventions in the successful management of aggression in persons with dementia. Management of aggression should include comprehensive assessment of medical, psychological, and environmental variables.