Lithium and Stroke Recovery: A Systematic Review and Meta-Analysis of Stroke Models in Rodents and Human Data.

BACKGROUND: Lithium has neuroprotective effects in animal models of stroke, but benefits in humans remain uncertain. This article aims to systematically review the available evidence of the neuroprotective and regenerative effects of lithium in animal models of stroke, as well as in observational and trial stroke studies in humans. METHODS: This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched Medline, Embase, and PsycINFO for preclinical and clinical studies published between January 2000 and September 2021. A random-effects meta-analysis was conducted from observational studies. RESULTS: From 1625 retrieved studies, 42 were included in the systematic review. Of those, we identified 36 rodent models of stroke using preinsult or postinsult treatment with lithium, and 6 studies were conducted in human samples, of which 4 could be meta-analyzed. The review of animal models was stratified according to the type of stroke and outcomes. Human data were subdivided into observational and intervention studies. Treatment of rodents with lithium was associated with smaller stroke volumes, decreased apoptosis, and improved poststroke function. In humans, exposure to lithium was associated with a lower risk of stroke among adults with bipolar disorder in 2 of 4 studies. Two small trials showed equivocal clinical benefits of lithium poststroke. CONCLUSIONS: Animal models of stroke show consistent biological and functional evidence of benefits associated with lithium treatment, whereas human evidence remains sparse and inconclusive. The potential role of lithium in poststroke recovery is yet to be adequately tested in humans.

Repeated Measures of Modified Rankin Scale Scores to Assess Functional Recovery From Stroke: AFFINITY Study Findings.

Background Function after acute stroke using the modified Rankin Scale (mRS) is usually assessed at a point in time. The analytical implications of serial mRS measurements to evaluate functional recovery over time is not completely understood. We compare repeated-measures and single-measure analyses of the mRS from a randomized clinical trial. Methods and Results Serial mRS data from AFFINITY (Assessment of Fluoxetine in Stroke Recovery), a double-blind placebo randomized clinical trial of fluoxetine following stroke (n=1280) were analyzed to identify demographic and clinical associations with functional recovery (reduction in mRS) over 12 months. Associations were identified using single-measure (day 365) and repeated-measures (days 28, 90, 180, and 365) partial proportional odds logistic regression. Ninety-five percent of participants experienced a reduction in mRS after 12 months. Functional recovery was associated with age at stroke <70 years; no prestroke history of diabetes, coronary heart disease, or ischemic stroke; prestroke history of depression, a relationship partner, living with others, independence, or paid employment; no fluoxetine intervention; ischemic stroke (compared with hemorrhagic); stroke treatment in Vietnam (compared with Australia or New Zealand); longer time since current stroke; and lower baseline National Institutes of Health Stroke Scale & Patient Health Questionnaire-9 scores. Direction of associations was largely concordant between single-measure and repeated-measures models. Association strength and variance was generally smaller in the repeated-measures model compared with the single-measure model. Conclusions Repeated-measures may improve trial precision in identifying trial associations and effects. Further repeated-measures stroke analyses are required to prove methodological value. Registration URL: http://www.anzctr.org.au; Unique identifier: ACTRN12611000774921.

Behavioral Activation in Nursing Homes to Treat Depression (BAN-Dep): Results From a Clustered, Randomized, Single-Blinded, Controlled Clinical Trial.

OBJECTIVES: To determine if behavioral activation (BA) delivered by trained staff decreases prevalence of clinically significant symptoms of depression among older adults living in residential aged care facilities (RACFs). METHODS: Clustered, randomized, single-blinded, controlled trial of BA for adults aged over 60 years living permanently in a RACF with symptoms of depression (Patient Health Questionnaire, PHQ-9 ≥ 5). BA was delivered over 8-12 weeks using a structured workbook. The proportion of residents with PHQ-9 ≥ 10 at weeks 12, 26, and 52, as well as anxiety symptoms (GAD-7), physical (PCS), and mental (MCS) quality of life, loneliness, and loss to follow-up were main outcomes of interest RESULTS: We recruited 54 RACFs (26 intervention) and 188 of their residents (89 intervention). Participants were aged 61-100 years and 132 (70.2%) were women. PHQ-9 ≥ 10 interacted with BA at week 12 (OR = 0.34, 95%CI = 0.11-1.07), but differences between the groups were not statistically significant at any time-point. GAD-7 ≥ 10 interacted with BA at week 26 (OR = 0.12, 95%CI = 0.02-0.58), but not at any other time-point. Overall, the intervention had no effect on the scores of the PHQ-9, GAD-7, PCS, MCS, and loneliness scale. Loss to follow-up was similar between groups. Adherence to all stages of the intervention was poor (36.2%). CONCLUSIONS: Disruption by the COVID-19 pandemic and staffing issues in RACFs undermined recruitment and adherence. In such a context, a BA program delivered by RACF staff was not associated with better mental health outcomes for residents over 52 weeks.

Hearing impairment and frailty in later life: The Health in Men Study (HIMS).

OBJECTIVE: To determine if hearing loss is associated with increased risk of frailty in later life. STUDY DESIGN: Cross-sectional study of a community sample of 4,004 men aged 70 years and above living in the metropolitan region of Perth, Western Australia. Data were retrieved from the Health in Men Study (HIMS) and the Western Australian Data Linkage System (WADLS). Frailty was assessed using the FRAIL scale and the Frailty Index. Hearing loss was defined by self-report or by diagnosis recorded in the WADLS. We also collected demographic, lifestyle and social support information. MAIN OUTCOME MEASURES: Frailty was assessed using the FRAIL scale and the Frailty Index. RESULTS: The prevalence of frailty in the sample population was 16.1% and 25.4% when assessed using the FRAIL scale and the Frailty Index respectively. After adjusting for participant demographic, lifestyle and social factors, hearing loss was significantly associated with the prevalence of frailty when diagnosed by either measure (FRAIL scale: odds ratio [OR] 1.59, 95 CI% 1.32 to 1.91; Frailty Index: OR 1.76, 95 CI% 1.50 to 2.05). The proportion of men with hearing loss increased with increasing severity of frailty. CONCLUSION: Hearing loss is associated with increased prevalence of frailty in older men when assessed using the FRAIL scale and the Frailty Index. Future longitudinal studies using objective measures of hearing will be helpful in determining if this association is likely to be causal.

Association between hearing loss and frailty: a systematic review and meta-analysis.

BACKGROUND: Frailty is associated with poor health outcomes in later life. Recent studies suggested that hearing loss may be a potentially modifiable risk factor associated with frailty. METHODS: This systematic review and meta-analysis aimed to investigate the association between hearing loss and frailty in observational studies of adults aged 50 years or over. We included observational studies with participants ≥ 50 years old that have clear descriptions of hearing and frailty measurement methods. Meta-analyses were conducted using measurement of risk and 95 % confidence interval of each individual study. Quality assessment, risk of bias, heterogeneity and sensitivity analyses were also conducted. Our study followed PRISMA guidelines. RESULTS: Our search identified 4508 manuscripts published in English between 1 and 2000 and 9 February 2021. Sixteen articles reported acceptable measurements of both hearing loss and frailty. Two papers were not suitable for meta-analysis. Twelve sets of cross-sectional data involving 12,313 participants, and three sets of longitudinal data involving 3042 participants were used in the meta-analysis. Hearing loss was associated with an 87 % increase in the risk of frailty among cross-sectional studies (risk ratio [RR] 1.87; 95 %CI 1.63-2.13) and 56 % among longitudinal studies (RR 1.56; 95 %CI 1.29-1.88). There was considerable heterogeneity among studies, but their quality rating, sample size or approach used to assess hearing loss did not change the results substantially. CONCLUSIONS: The findings of this systematic review and meta-analysis of observational studies suggest that hearing loss increases the risk of frailty in later life. Whether this relationship is causal remains to be determined.

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration.

BACKGROUND AND PURPOSE: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. METHODS: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. RESULTS: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76-1.14]; P=0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P=0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P=0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P=0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P=0.64) at 12 months. CONCLUSIONS: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/; Unique identifier: ACTRN12611000774921.

Obstructive sleep apnea and depression: A systematic review and meta-analysis.

INTRODUCTION: The present study aimed to review the association between obstructive sleep apnea (OSA) and depression and compare the prevalence of depression among people with and without OSA. METHODS: Systematic review and meta-analysis following PRISMA guidelines. We searched for papers published between 1 January 2010 and 20 October 2019 listed on the following databases: Embase, Ovid MEDLINER(R) and PsychINFO. The search terms included a combination of keywords related to sleep apnea and depression. We also completed a manual search of the references listed in the articles retrieved and grouped them according to study design: cross-sectional, case-control and longitudinal. Scale scores were standardised for comparison. RESULTS: Our search strategy yielded 1158 papers, of which 34 were considered suitable of review and 11 reported data that could be used for meta-analysis. Data from the 6 cross-sectional studies found no compelling evidence of an association between OSA and depression (odds ratio = 1.12, 95 % confidence interval, 95 %CI = 0.78, 1.47), but the meta-analysis of 5 longitudinal studies indicated that people with OSA were at greater risk of developing depression during follow-up than those without OSA (non-specific risk ratio (RR) = 2.18, 95 %CI = 1.47, 2.88), although there was evidence of high study heterogeneity (I2 = 72.8 %). DISCUSSION: The results of this systematic review and meta-analysis of observational studies is consistent with the hypothesis that OSA may increase the risk of depression. Sample characteristics and various methodological issues create uncertainty about the validity and generalizability of these associations.

Hearing aids to support cognitive functions of older adults at risk of dementia: the HearCog trial- clinical protocols.

BACKGROUND: Globally, about 50 million people were living with dementia in 2015, with this number projected to triple by 2050. With no cure or effective treatment currently insight, it is vital that factors are identified which will help prevent or delay both age-related and pathological cognitive decline and dementia. Observational data have suggested that hearing loss is a potentially modifiable risk factor for dementia, but no conclusive evidence from randomised controlled trials is currently available. METHODS: The HearCog trial is a 24-month, randomised, controlled clinical trial aimed at determining whether a hearing loss intervention can delay or arrest the cognitive decline. We will randomise 180 older adults with hearing loss and mild cognitive impairment to a hearing aid or control group to determine if the fitting of hearing aids decreases the 12-month rate of cognitive decline compared with the control group. In addition, we will also determine if the expected clinical gains achieved after 12 months can be sustained over an additional 12 months and if losses experienced through the non-correction of hearing loss can be reversed with the fitting of hearing aids after 12 months. DISCUSSION: The trial will also explore the cost-effectiveness of the intervention compared to the control arm and the impact of hearing aids on anxiety, depression, physical health and quality of life. The results of this trial will clarify whether the systematic correction of hearing loss benefits cognition in older adults at risk of cognitive decline. We anticipate that our findings will have implications for clinical practice and health policy development. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ANZCTR: 12618001278224 ), registered on 30.07.2018.

The Healthy Heart-Mind Trial: Randomized Controlled Trial of Melatonin for Prevention of Delirium.

OBJECTIVES: Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery. DESIGN: Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design). SETTING: The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia. PARTICIPANTS: We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery. INTERVENTION: Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery. MEASUREMENTS: The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery. RESULTS: The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] = .78; 95% confidence interval [CI] = .35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = -1.03; P = .304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ2 = .93; P = .334; adjusted OR = 1.98; 95% CI = .40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance. CONCLUSION: The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery. J Am Geriatr Soc 68:112-119, 2019.

Behavioural activation in nursing homes to treat depression (BAN-Dep): study protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Depression is a common disorder among older people living in residential aged care facilities. Several trials have demonstrated the effectiveness of behavioural therapies in treating depressive symptoms in older adults living in the community and in residential aged care. Behavioural Activation is demonstrably effective even when delivered by non-specialists (staff without formal psychological training), although strategies for adapting its use in residential aged care facilities are yet to be explored. This study will determine whether training residential care staff in the use of a structured Behavioural Activation programme is more effective at decreasing depressive symptoms among older residents than internet-based training about depression recognition and management alone. METHOD AND ANALYSIS: The behavioural activation in nursing homes to treat depression (BAN-Dep) trial is a pragmatic two-arm parallel clustered randomised controlled trial. It will recruit 666 residents aged 60 or older from 100 residential aged care facilities, which will be randomly assigned to the Behavioural Activation or control intervention. Staff in both treatment groups will be encouraged to complete the Beyondblue Professional Education to Aged Care e-learning programme to improve their recognition of and ability to respond to depression in older adults. Selected staff from intervention facilities will undergo additional training to deliver an 8-module Behavioural Activation programme to residents with subthreshold symptoms of depression-they will receive ongoing Mental support from trained Behavioural Activation therapists. Outcome measures will be collected by blind research officer at baseline and after 3, 6 and 12 months. The Patient Health Questionnaire-9 is the primary outcome measure of the study. ETHICS AND DISSEMINATION: The trial will comply with the principles of the Declaration of Helsinki for Human Rights and is overseen by the University of Western Australia (reference RA/4/20/4234) and Melbourne Health (reference number HREC/18/MH/47) Ethics Committees. The results of this research project will be disseminated through publications and/or presentations in a variety of media to health professionals, academics, clinicians and the public. Only de-identified group data will be presented. TRIAL REGISTRATION: ACTRN12618000634279.

Depression, antidepressants and the risk of cardiovascular events and death in older men.

INTRODUCTION: It is uncertain whether depression and exposure to antidepressants increase the risk of cardiovascular events in later life. This study attempts to clarify whether the risk of cardiovascular events associated with exposure to antidepressant medications varies according to history of depression. METHODS: Cohort study of 5522 Australian men aged 70-89 years living in the metropolitan region of Perth, Western Australia, who were followed for novel cardiovascular events over 12 years. Clinical diagnoses followed the International Classification of Diseases (ICD) codes for ischaemic heart disease, cerebrovascular events and depressive disorders. Participants self-reported their use of medications. Other study measures included age, schooling, smoking history and the following concurrent morbidities: diabetes, hypertension, cancer, dementia, and respiratory diseases, gastrointestinal and renal diseases. RESULTS: 374 men (6.8%) had a recorded or current diagnosis of depression and 365 (6.6%) were using an antidepressant. Prevalent depression and antidepressant use were associated with increased mortality hazard, but not the interaction between them (hazard ratio, HR = 0.46, 95%CI = 0.33, 0.65). Depression (HR = 1.50, 95%CI = 1.21, 1.86) and antidepressants (HR = 1.52, 95%CI = 1.20, 1.93) were associated with an increased risk of cardiovascular events, but the interaction term was associated with decreased risk (HR = 0.51, 95%CI = 0.30, 0.87). All analyses were adjusted for other study measures. DISCUSSION: Depression and antidepressant use were associated with an increase in the 12-year risk of cardiovascular events, while antidepressants were associated with a decrease in the risk of cardiovascular events among older men with depression, but not among those without. This suggests that the effect of this interaction on the risk of cardiovascular events may be driven by the ability of antidepressants to lead to clinical improvements in mood.

Effect of Vitamin B Supplementation on Cognitive Function in the Elderly: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin B deficiency and elevated total plasma homocysteine have been associated with cognitive impairment and dementia in later life, although it is unknown if treatment with these vitamins improves cognitive outcomes. OBJECTIVES: The objectives of this study were to examine the efficacy of treatment with vitamin B12, vitamin B6, or folic acid in slowing cognitive decline amongst older adults with and without cognitive impairment. METHODS: We summarized findings from previous systematic reviews of clinical trials and performed a new systematic review and meta-analysis of 31 English-language, randomized placebo-controlled trials of B-vitamin supplementation of individuals with and without existing cognitive impairment. RESULTS: Previous reviews have generally reported no effect of B vitamins on cognitive function in older adults with or without cognitive impairment at study entry, although these vitamins effectively lowered total plasma homocysteine levels in participants. Ten randomized placebo-controlled trials of 1925 participants with pre-existing cognitive impairment and 21 trials of 15,104 participants without cognitive impairment have been completed to date but these generally confirmed findings from previous reviews with the exception of two trials that showed a modest but clinically uncertain benefit for vitamins in people with elevated plasma homocysteine. B-vitamin supplementation did not show an improvement in Mini-Mental State Examination scores for individuals with (mean difference 0.16, 95% confidence interval - 0.18 to 0.51) and without (mean difference 0.04, 95% confidence interval - 0.10 to 0.18) cognitive impairment compared to placebo. CONCLUSIONS: Raised total plasma homocysteine is associated with an increased risk of cognitive impairment and dementia, although available evidence from randomized controlled trials shows no obvious cognitive benefit of lowering homocysteine using B vitamins. Existing trials vary greatly in the type of supplementation, population sampled, study quality, and duration of treatment, thereby making it difficult to draw firm conclusions from existing data. Findings should therefore be viewed in the context of the limitations of the available data and the lack of evidence of effect should not necessarily be interpreted as evidence of no effect.

Risk of dementia associated with psychotic disorders in later life: the health in men study (HIMS).

BACKGROUND: Recent research has identified several potentially modifiable risk factors for dementia, including mental disorders. Psychotic disorders, such as schizophrenia and delusional disorder, have also been associated with increased risk of cognitive impairment and dementia, but currently available data difficult to generalise because of bias and confounding. We designed the present study to investigate if the presence of a psychotic disorder increased the risk of incident dementia in later life. METHODS: Prospective cohort study of a community-representative sample of 37 770 men aged 65-85 years who were free of dementia at study entry. They were followed for up to 17.7 years using electronic health records. Clinical diagnoses followed the International Classification of Diseases guidelines. As psychotic disorders increase mortality, we considered death a competing risk. RESULTS: A total of 8068 (21.4%) men developed dementia and 23 999 (63.5%) died during follow up. The sub-hazard ratio of dementia associated with a psychotic disorder was 2.67 (95% CI 2.30-3.09), after statistical adjustments for age and prevalent cardiovascular, respiratory, gastrointestinal and renal diseases, cancer, as well as hearing loss, depressive and bipolar disorders, and alcohol use disorder. The association between psychotic disorder and dementia risk varied slightly according to the duration of the psychotic disorder (highest for those with the shortest illness duration), but not the age of onset. No information about the use of antipsychotics was available. CONCLUSION: Older men with a psychotic disorder have nearly three times greater risk of developing dementia than those without psychosis. The pathways linking psychotic disorders to dementia remain unclear but may involve mechanisms other than those associated with Alzheimer's disease and other common dementia syndromes.

Hearing loss and incident psychosis in later life: The Health in Men Study (HIMS).

OBJECTIVE: To determine if hearing loss is associated with increased risk of incident psychosis in later life. METHODS: Longitudinal cohort study of a community-representative sample of 38 173 men aged 65 to 85 years at the start of the follow-up period of 18 years. We used the Western Australian Data Linkage System to ascertain the presence of hearing loss and of psychotic disorders according to the International Classification of Diseases (ICD) (versions 8, 9, and 10). We also collected information on concurrent morbidities: cancer and diseases of the cardiovascular, respiratory, digestive, and renal systems. RESULTS: One thousand four hundred forty-two (3.8%) and 464 (1.2%) men had a recorded diagnosis of hearing loss and psychosis at the start of follow-up. After excluding the 464 participants with prevalent psychosis, 37 709 men were available for the longitudinal study, and of these, 252 (0.7%) developed a psychotic disorder. Competing risk regression showed that hearing loss was associated incident psychosis (subhazard ratio = 2.03, 95% CI, 1.24-3.32; after statistical adjustment for age and concurrent morbidities). CONCLUSIONS: Hearing loss is associated with double the risk of incident psychosis in older men. Available evidence suggests that this link could be causal, although conclusive evidence is still missing from randomized controlled trials designed to test the effect of correction of hearing loss on the prevalence and incidence of psychosis.

Sex hormones and incident dementia in older men: The health in men study.

BACKGROUND: Low circulating testosterone has been associated with dementia in older men but existing evidence from prospective studies is inconsistent. METHODS: We conducted a prospective longitudinal study of 4069 community-dwelling older men free of dementia aged 71-88 years at baseline. The main objective of the study was to determine if men with low circulating sex hormones were more likely to develop dementia over time. The main biochemical exposures of interest were collected at baseline between 2001 and 2004 and men were assessed for incident dementia via an electronic health records database to the 31 st of December 2013. RESULTS: Dementia developed in 499 men over a median of 10.5 years (range 9.4-12.2 years). The risk of developing dementia increased with decreasing total (hazard ratio [HR] 1.14, 95% confidence interval [95%CI] 1.03-1.26 per standard deviation decrease) and calculated free testosterone (HR 1.18, 95%CI 1.06-1.31 per standard deviation decrease) after adjustment for age, baseline cognitive function, depression, body mass, hypertension, cardiovascular disease and total plasma homocysteine. Men in the lowest quartiles of total (adjusted HR 1.39, 95%CI 1.04-1.85) and calculated free testosterone (adjusted HR 1.43, 95%CI 1.08-1.90) had increased risk of developing dementia compared to those in the highest quartiles. CONCLUSIONS: Lower plasma total and calculated free testosterone were associated with increased risk of developing dementia independent of relevant measured clinical and biochemical factors and was not explained due to differential mortality in those with lower testosterone levels. The association between low testosterone and dementia is biologically plausible but data on the role of testosterone treatment in preventing dementia is lacking and adequately powered trials in men at risk would be welcome.

Hearing loss and the risk of dementia in later life.

Dementia is a major source of disability worldwide and there are currently no available disease-modifying treatments. Hearing loss may be associated with increased risk of dementia in later life and therefore could be a modifiable risk factor, given the availability of efficacious interventions. We investigated the association of hearing loss and dementia through two complementary approaches: a prospective, cohort study of 37,898 older men (mean age 72.5 ±â€¯4.6 years) with a mean follow-up of 11.1 years, and a systematic review and meta-analysis of prospective studies. In our cohort, men with hearing loss were more likely to develop dementia (n = 6948, 18.3%) than men free of significant hearing impairment - adjusted hazard ratio 1.69, 95% CI = 1.54-1.85. In our review, the aggregated hazard of dementia was 1.49 (95% CI 1.30-1.67) in those with hearing impairment (14 included studies). Study quality, duration and dementia type did not alter the results considerably. We found an increased risk of incident dementia with hearing impairment in both our novel data and the meta-analysis. This is an important finding, particularly in light of recent suggestions that mid-life hearing loss may account for up to 9.1% of dementia cases worldwide, and efforts to reduce its impact should continue to be explored.

Management of Depression in Patients with Dementia: Is Pharmacological Treatment Justified?

Depression in the context of dementia is common and contributes to poorer outcomes in individuals and those who care for them. Non-pharmacological treatments are the preferred initial approach to managing these symptoms but data in support of these are scarce. There are a number of pharmacological treatment options available to clinicians but efficacy is uncertain and concern about potential side effects in an aging and vulnerable population needs to be taken into consideration. This review aims to provide a concise overview of pharmacological treatments for depression in dementia. Antidepressants are the mainstay of pharmacological treatment for clinically significant depression in the general population but evidence to support their use in dementia is mixed. Trials of antidepressants should generally be reserved for individuals with depression where the symptoms are distressing and surpass the threshold for major depression. Acetylcholinesterase inhibitors and memantine are effective in the symptomatic treatment of Alzheimer's disease but current evidence does not support their use to treat depressive symptoms in dementia. Similarly, antipsychotics and mood stabilizers have no proven efficacy for depression and the risk of adverse effects seems to outweigh any potential benefit. Pain can be a frequent problem in dementia and may have significant effects on behavior and mood. Preliminary evidence supports a role of adequate analgesia in improving mood in people with dementia.

Preventing delirium in dementia: Managing risk factors.

Delirium is a common, disabling medical condition that is associated with numerous adverse outcomes. A number of inter-related factors, including pre-existing cognitive impairment, usually contribute to the development of delirium in a particular susceptible individual. Non-pharmacological approaches to prevention typically target multiple risk factors in a systematic manner (multicomponent interventions). There is generally good evidence that multicomponent interventions reduce the incidence of delirium in hospital populations but there are limited data in people with dementia and those living in the community. It is likely that there is a differential effect of specific interventions in those with cognitive impairment (e.g. people with dementia may respond better to simpler, more pragmatic interventions rather than complex procedures) but this cannot be determined from the existing data. Targeted interventions focussed on hydration, medication rationalization and sleep promotion may also be effective in reducing the incidence of delirium, as well as the active involvement of family members in the care of the elderly hospitalized patient. Hospitalization itself is a potential risk factor for delirium and promising data are emerging of the benefits of home-based care as an alternative to hospitalization but this is restricted to specific sub-populations of patients and is reliant on these services being available.