Osvaldo P. Almeida

Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease: A Randomized Trial

CONTEXT Many observational studies have shown that physical activity reduces the risk of cognitive decline; however, evidence from randomized trials is lacking. OBJECTIVE To determine whether physical activity reduces the rate of cognitive decline among older adults at risk. DESIGN AND SETTING Randomized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth, Western Australia. Assessors of cognitive function were blinded to group membership. PARTICIPANTS We recruited volunteers who reported memory problems but did not meet criteria for dementia. Three hundred eleven individuals aged 50 years or older were screened for eligibility, 89 were not eligible, and 52 refused to participate. A total of 170 participants were randomized and 138 participants completed the 18-month assessment. INTERVENTION Participants were randomly allocated to an education and usual care group or to a 24-week home-based program of physical activity. MAIN OUTCOME MEASURE Change in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores (possible range, 0-70) over 18 months. RESULTS In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention. The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention. At 18 months, participants in the intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog, and those in the usual care group improved 0.04 points (95% confidence interval, -0.46 to 0.88). Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well, whereas word list total immediate recall, digit symbol coding, verbal fluency, Beck depression score, and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly. CONCLUSIONS In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12605000136606.

Short versions of the geriatric depression scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV

To determine the validity of short Geriatric Depression Scale (GDS) versions for the detection of a major depressive episode according to ICD‐10 criteria for research and DSM‐IV.

CONFIABILIDADE DA VERSAO BRASILEIRA DA ESCALA DE DEPRESSAO EM GERIATRIA (GDS) VERSAO REDUZIDA

Depression is a frequent health problem in old age, although the detection of such cases in clinical practice is often difficult. The systematic use of depression rating scales may increase diagnostic rates of depression amongst the elderly. This study aimed to assess the test-retest reliability of short versions of the Geriatric Depression Scale (GDS) with 1, 4, 10, and 15 items. Sixty-four consecutive patients aged 60 or over attending the outpatient clinic for the elderly (UNID) at the Department of Mental Health of Santa Casa of São Paulo were recruited for the study between February and May 1998. All subjects fulfilled criteria for the diagnosis of a depressive disorder (current or in remission) according to ICD-10, and had Mini Mental State scores greater than 10. They were evaluated twice in 48 to 72 hours with the GDS-15. Fifty-one patients completed both assessments. Agreement between scores for individual items was evaluated with Kappa statistic. Kappa coefficients ranged from 0.04 to 0.49, indicating that there was much variation within individual items. Total GDS-15 scores were reasonably stable, as assessed by paired Wilcoxon (z = 1.60, p = 0.109), Spearman correlation coefficient (rho = 0.86, p < 0.001), and weighted Kappa (Kappa = 0.64). The same pattern was also observed for the total scores of the GDS-10 on the paired Wilcoxon (z = 0.85, p = 0.402), Spearman correlation coefficient (rho = 0.81, p < 0.001), and weighted Kappa (Kappa = 0.60). Total score for the GDS-4 showed significant changes from test to retest (z = 3.75, p < 0.001; rho = 0.56, p < 0.001; Kappa = 0.37). These results indicate that the short GDS versions with 1 and 4 items are unreliable for use in clinical practice. In contrast, the GDS with 10 and 15 items produced consistent results in the assessment of elderly patients when total scores were used as clinical guidelines.Depressao e problema de saude frequente entre idosos, embora a identificacao desses pacientes seja muitas vezes dificil na pratica clinica. Nesse sentido, a avaliacao sistematica dos individuos nessa faixa etaria pode contribuir para melhorar a deteccao dos casos de depressao. Este estudo foi desenhado com o objetivo de avaliar a confiabilidade de teste-reteste das versoes com 15, 10, 4, e 1 itens da Escala de Depressao em Geriatria (GDS). Foram selecionados 64 individuos com 60 ou mais anos de idade atendidos de forma consecutiva nos ambulatorios da Unidade de Idosos do Departamento de Saude Mental da Santa Casa de Sao Paulo entre fevereiro e maio de 1998. Todos preenchiam criterios para o diagnostico de transtorno depressivo (em remissao ou atual) de acordo com a CID-10 e apresentavam escores maiores do que 10 no Mini-Exame do Estado Mental. Eles foram avaliados duas vezes com a GDS-15, sendo as entrevistas conduzidas com intervalo de 48 a 72 horas. Cinquenta e um pacientes aceitaram participar do estudo. A concordância entre os escores de itens individuais da escala foi avaliada pelo coeficiente estatistico Kappa. Estes oscilaram entre 0,04 e 0,49, indicando baixa estabilidade na resposta dos pacientes. Os escores totais da GDS-15 mantiveram-se relativamente estaveis durante o reteste, conforme indicado pelo teste pareado de Wilcoxon (z=1,60; p=0,109), correlacao de Spearman (rho=0,86; p<0,001), e Kappa ponderado (Kappa=0,64). O mesmo padrao foi observado para a GDS-10 no teste de Wilcoxon (z=0,85; p=0,402), Spearman (rho=0,81; p<0,001), e Kappa ponderado (Kappa=0,60). O escore total da GDS-4 mostrou variacoes significativas do teste para o reteste (z=3,75; p<0,001; rho=0,56; p<0,001; Kappa=0,37). Esses resultados indicam que as versoes com 1 e 4 itens apresentam baixos coeficientes de confiabilidade. Isso sugere que essas versoes tem utilidade clinica limitada. Por outro lado, a GDS com 15 e 10 iitens pode ser utilizada com relativa confiabilidade na pratica clinica, particularmente quando se consideram os escores totais das escalas.

A systematic review of the association between the Behavioral and Psychological Symptoms of Dementia and burden of care

BACKGROUND Several reports have indicated that the Behavioral and Psychological Symptoms of Dementia (BPSD) are associated with increased burden of care, carer depression and increased rates of institutionalization of patients. The present study aims to review the association between these variables in cross-sectional as well as longitudinal studies. METHODS Systematic review and meta-analysis of all available information published in English between January 1990 and December 2001 was made. Case-reports, case-series and studies with 20 or fewer subjects were excluded from the analyses. RESULTS Thirty articles are included in the review of cross-sectional data and 12 in the systematic review of longitudinal data. Pooled correlation coefficients were generated for the relationship between BPSD and caregiver burden (r(pooled) = 0.57; 95% CI = 0.52 to 0.62), caregiver psychological distress (r(pooled) = 0.41; 95% CI = 0.32 to 0.49) and caregiver depression (r(pooled) = 0.30; 95% CI= 0.21 to 0.39), suggesting that these concepts have a moderately strong association. Multivariate data, on the whole, further supported the notion that BPSD are a predictor of burden of care and of psychological distress and depression. Limited longitudinal data made clarifying the temporal relationahip between BPSD and the psychological sequelae of care (PSC) difficult. The limited data pertaining to the relationship between BPSD and institutionalization suggest that caregiver variables may be more important in predicting institutionalization than BPSD. Methodological issues and limitations associated with this type of investigation were also considered. CONCLUSION The results of this review support, but do not conclusively establish, the association between BPSD and PSC. We propose that the concept of burden of care be abandoned in favor of more clinically relevant outcomes such as caregiver depression.

Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials

Summary Background The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C→T and stroke in a genetic analysis and meta-analysis of randomised controlled trials. Methods We established a collaboration of genetic studies consisting of 237 datasets including 59 995 individuals with data for homocysteine and 20 885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45 549 individuals, 2314 stroke events, 269 transient ischaemic attacks). Findings The effect of the MTHFR 677C→T variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3·12 μmol/L, 95% CI 2·23 to 4·01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0·13 μmol/L, −0·85 to 1·11). The odds ratio (OR) for stroke was also higher in Asia (1·68, 95% CI 1·44 to 1·97) than in America, Australia, and New Zealand, high (1·03, 0·84 to 1·25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0·94, 95% CI 0·85 to 1·04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar folate status (predicted RR 1·00, 95% CI 0·90 to 1·11). Although the predicted effect of homocysteine reduction from large genetic studies in low folate regions (Asia) was larger (RR 0·78, 95% CI 0·68 to 0·90), no trial has evaluated the effect of lowering of homocysteine on stroke risk exclusively in a low folate region. Interpretation In regions with increasing levels or established policies of population folate supplementation, evidence from genetic studies and randomised trials is concordant in suggesting an absence of benefit from lowering of homocysteine for prevention of stroke. Further large-scale genetic studies of the association between MTHFR 677C→T and stroke in low folate settings are needed to distinguish effect modification by folate from small-study bias. If future randomised trials of homocysteine-lowering interventions for stroke prevention are undertaken, they should take place in regions with low folate consumption. Funding Full funding sources listed at end of paper (see Acknowledgments).

Long-term effects of childhood abuse on the quality of life and health of older people: results from the depression and early prevention of suicide in general practice project

OBJECTIVES: To determine whether childhood physical and sexual abuse are associated with poor mental and physical health outcomes in older age.

Cohort Profile: The Health In Men Study (HIMS)

The Health In Men Study (HIMS) arose out of a population-based randomized trial of screening for abdominal aortic aneurysms (AAAs) conducted in Perth, Western Australia in 1996–99. Only men aged 65 years and over were recruited into the trial as AAAs are uncommon below this age and are six times more common in men than women. The aim of the trial was to assess whether screening reduced mortality from AAA. Secondary outcomes included assessments of the impact of screening on all-cause mortality and quality of life and a study of the rates of expansion of screen-detected AAAs.

Lower Testosterone Levels Predict Incident Stroke and Transient Ischemic Attack in Older Men

CONTEXT Lower circulating testosterone concentrations are associated with metabolic syndrome, type 2 diabetes, carotid intima-media thickness, and aortic and lower limb arterial disease in men. However, it is unclear whether lower testosterone levels predict major cardiovascular events. OBJECTIVE We examined whether lower serum testosterone was an independently significant risk factor for symptomatic cerebrovascular events in older men. DESIGN This was a prospective observational study with median follow-up of 3.5 yr. SETTING Community-dwelling, stroke-free older men were studied. PARTICIPANTS A total of 3443 men at least 70 yr of age participated in the study. MAIN OUTCOME MEASURES Baseline serum total testosterone, SHBG, and LH were assayed. Free testosterone was calculated using mass action equations. Incident stroke or transient ischemic attack (TIA) was recorded. RESULTS A first stroke or TIA occurred in 119 men (3.5%). Total and free testosterone concentrations in the lowest quartiles (<11.7 nmol/liter and <222 pmol/liter) were associated with reduced event-free survival (P = 0.014 and P = 0.01, respectively). After adjustment including age, waist-hip ratio, waist circumference, smoking, hypertension, dyslipidemia, and medical comorbidity, lower total testosterone predicted increased incidence of stroke or TIA (hazard ratio = 1.99; 95% confidence interval, 1.33-2.99). Lower free testosterone was also associated (hazard ratio = 1.69; 95% confidence interval, 1.15-2.48), whereas SHBG and LH were not independently associated with incident stroke or TIA. CONCLUSIONS In older men, lower total testosterone levels predict increased incidence of stroke or TIA after adjusting for conventional risk factors for cardiovascular disease. Men with low-normal testosterone levels had increased risk. Further studies are warranted to determine whether interventions that raise circulating testosterone levels might prevent cerebrovascular disease in men.

Low Free Testosterone Predicts Frailty in Older Men: The Health in Men Study

CONTEXT The prevalence of frailty increases, whereas testosterone decreases, as men age. Low testosterone may be a risk factor for development of this syndrome. OBJECTIVE Our objective was to determine whether testosterone levels are associated with frailty. DESIGN We conducted a prospective cohort study. SETTING AND PARTICIPANTS Between 2001 and 2004, frailty was assessed in 3616 community-dwelling men aged 70-88 yr. Frailty was reassessed in 1586 men aged 76-93 yr in 2008-2009. MAIN OUTCOME MEASURES Frailty was assessed with the FRAIL scale, comprising five domains: fatigue, difficulty climbing a flight of stairs, difficulty walking more than 100 m, more than five illnesses present, or weight loss greater than 5%. Testosterone, SHBG, and LH were assayed at baseline. Free testosterone was calculated using mass action equations. RESULTS At baseline, 15.2% of men (n = 548) were frail (at least three deficits), increasing to 23.0% (n = 364) at follow-up. At baseline, each 1 sd decrease in total or free testosterone level was associated with increased odds of frailty [odds ratio (OR) = 1.23; 95% confidence interval (CI) = 1.11-1.38, and OR = 1.29; 95% CI = 1.15-1.44 for total and free testosterone, respectively]. Lower LH was associated with reduced odds of frailty (OR = 0.88; 95% CI = 0.81-0.95). Adjustments were made for age, body mass index, smoking, diabetes, social support, and other covariates. At follow-up, only lower free testosterone levels (OR = 1.22; 95% CI = 1.05-1.42) predicted frailty. CONCLUSIONS Lower free testosterone was independently associated with frailty at baseline and follow-up. Randomized trials should explore whether testosterone therapy can prevent the development of frailty.

The mind of a failing heart: a systematic review of the association between congestive heart failure and cognitive functioning.

Abstract