Common Versus Uncommon Causes of Dementia

When patients present with a dementia syndrome at a young age, the experienced clinician will automatically include uncommon dementias in the diagnostic considerations, as familial uncommon dementias due to genetic mutations frequently present as early-onset dementias. This paper highlights why uncommon dementias due to genetic mutations, although marginal in terms of prevalence numbers in the total population, are of significance in the quest to unravel the underlying cause of common dementias such as Alzheimer\u27s disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD) and vascular dementia (VaD)

Can physical activity improve the mental health of older adults?

The world population is aging rapidly. Whilst this dramatic demographic change is a desirable and welcome phenomenon, particularly in view of people's increasing longevity, it's social, financial and health consequences can not be ignored. In addition to an increase of many age related physical illnesses, this demographic change will also lead to an increase of a number of mental health problems in older adults and in particular of dementia and depression. Therefore, any health promotion approach that could facilitate introduction of effective primary, secondary and even tertiary prevention strategies in old age psychiatry would be of significant importance. This paper explores physical activity as one of possible health promotion strategies and evaluates the existing evidence that supports its positive effect on cognitive impairment and depression in later life

Repurposing Proteostasis-Modifying Drugs to Prevent or Treat Age-Related Dementia: A Systematic Review

Background: Dementia has a significant impact on quality of life of older individuals. Impaired proteostasis has been implicated as a potential cause of dementia, that can be therapeutically targeted to improve patient outcomes. This review aimed to collate all current evidence of the potential for targeting proteostasis with repurposed drugs as an intervention for age-related dementia and cognitive decline.Methods: PubMed, Web of Science and Embase databases were searched from inception until 4th July 2017 for studies published in English. Interventional studies of repurposed proteostasis-modifying drugs in Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body disease, vascular dementia, and cognitive aging, in either animal models or humans with change in cognition as the outcome were included. The SYRCLE and Cochrane tools were used to assess risk of bias for included studies.Results: Overall 47 trials, 38 animal and 9 human, were isolated for inclusion in this review. Drugs tested in animals and humans included lithium, rapamycin, rifampicin, and tyrosine kinase inhibitors. Drugs tested only in animals included Macrophage and Granulocyte-Macrophage Colony Stimulating Factors, methylene blue, dantrolene, geranylgeranylacetone, minocycline and phenylbutyric acid. Lithium (n = 10 animal, n = 6 human) and rapamycin (n = 12 animal, n = 1 human) were the most studied proteostasis modifying drugs influencing cognition. Nine of ten animal studies of lithium showed a statistically significant benefit in Alzheimer's models. Rapamycin demonstrated a significant benefit in models of vascular dementia, aging, and Alzheimer's, but may not be effective in treating established Alzheimer's pathology. Lithium and nilotinib had positive outcomes in human studies including Alzheimer's and Parkinson's patients respectively, while a human study of rifampicin in Alzheimer's failed to demonstrate benefit. Microdose lithium showed a strongly significant benefit in both animals and humans. While the risk of bias was relatively low in human studies, the risk of bias in animal studies was largely unclear.Conclusion: Overall, the collective findings support the hypothesis that targeting proteostasis for treatment of dementia may be beneficial, and therefore future studies in humans with repurposed proteostasis modifying drugs are warranted. Larger human clinical trials focusing on safety, efficacy, tolerability, and reproducibility are required to translate these therapeutics into clinical practice

Mortality in a cohort of remote-living aboriginal Australians and associated factors

Objectives: We aimed to describe mortality in a cohort of remote-living Aboriginal Australians using electronic record linkage. Methods: Between 2004 and 2006, 363 Aboriginal people living in remote Western Australia (WA) completed a questionnaire assessing medical history and behavioural risk factors. We obtained mortality records for the cohort from the WA Data Linkage System and compared them to data for the general population. We used Cox proportional hazards regression to identify predictors of mortality over a 9-year follow-up period. Results: The leading causes of mortality were diabetes, renal failure, and ischaemic heart disease. Diabetes and renal failure accounted for 28% of all deaths. This differed from both the Australian population as a whole, and the general Indigenous Australian population. The presence of chronic disease did not predict mortality, nor did behaviours such as smoking. Only age, male sex, poor mobility, and cognitive impairment were risk factors. Conclusions: To reduce premature mortality, public health practitioners should prioritise the prevention and treatment of diabetes and renal disease in Aboriginal people in remote WA. This will require a sustained and holistic approach

Falls, Depression and antidepressants in Later Life: A Large Primary Care Appraisal

Background: Depression and falls are common and co-exist for older people. Safe management of each of these conditions is important to quality of life. Methods: A cross-sectional survey was used to examine medication use associated with injurious and non-injurious falls in 21,900 community-dwelling adults, aged 60 years or over from 383 Australian general practices recruited for the DEPS-GP Project. Falls and injury from falls, medication use, depressive symptoms (Primary Health Questionnaire (PHQ-9)), clinical morbidity, suicidal ideation and intent, health status (SF-12 Health Survey), demographic and lifestyle information was reported in a standardised survey. Findings: Respondents were 71.8 years (sd 7.7) of age and 58.4% were women. 24% 11% and 8% reported falls, fall related injury, and sought medical attention respectively. Antidepressant use (odds ratio, OR: 1.46; 95% confidence interval, 95%CI: 1.25, 1.70), questionable depression (5–14 on PHQ OR: 1.32, 95%CI: 1.13, 1.53) and clinically significant symptoms of depression (15 or more on PHQ OR: 1.70, 95%CI: 1.14, 1.50) were independently associated with multiple falls. SSRI use was associated with the highest risk of multiple falls (OR: 1.66, 95%CI: 1.36, 2.02) amongst all psychotropic medications. Similar associations were observed for injurious falls. Over 60% of those with four accumulated risk factors had multiple falls in the previous year (OR: 3.40, 95%CI: 1.79, 6.45); adjusted for other demographic and health factors. Interpretation: Antidepressant use (particularly SSRIs) was strongly associated with falls regardless of presence of depressive symptoms. Strategies to prevent falls should become a routine part of the management of older people with depression

Homocysteine, grey matter and cognitive function in adults with cardiovascular disease

Background: Elevated total plasma homocysteine (tHcy) has been associated with cognitive impairment, vascular disease and brain atrophy. Methods: We investigated 150 volunteers to determine if the association between high tHcy and cerebral grey matter volume and cognitive function is independent of cardiovascular disease. Results: Participants with high tHcy (≥15 μmol/L) showed a widespread relative loss of grey matter compared with people with normal tHcy, although differences between the groups were minimal once the analyses were adjusted for age, gender, diabetes, hypertension, smoking and prevalent cardiovascular disease. Individuals with high tHcy had worse cognitive scores across a range of domains and less total grey matter volume, although these differences were not significant in the adjusted models. Conclusions: Our results suggest that the association between high tHcy and loss of cerebral grey matter volume and decline in cognitive function is largely explained by increasing age and cardiovascular diseases and indicate that the relationship is not causal

Anxiety, depression and comorbid anxiety and depression: risk factors and outcome over two years

Background: This study aimed to determine: (1) the prevalence of depression, anxiety, and depression associated with anxiety (DA); (2) the risk factor profile of depression, anxiety, and DA; (3) the course of depression, anxiety, and DA over 24 months. Methods: Two-year longitudinal study of 20,036 adults aged 60+ years. We used the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale anxiety subscale to establish the presence of depression and anxiety, and standard procedures to collect demographic, lifestyle, psychosocial, and clinical data. Results: The prevalence of anxiety, depression, and DA was 4.7%, 1.4%, and 1.8%. About 57% of depression cases showed evidence of comorbid anxiety, while only 28% of those with clinically significant anxiety had concurrent depression. There was not only an overlap in the distribution of risk factors in these diagnostic groups but also differences. We found that 31%, 23%, and 35% of older adults with anxiety, depression, and DA showed persistence of symptoms after two years. Repeated anxiety was more common in women and repeated depression in men. Socioeconomic stressors were common in repeated DA. Conclusions: Clinically significant anxiety and depression are distinct conditions that frequently coexist in later life; when they appear together, older adults endure a more chronic course of illness