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Depression is an accepted risk factor for dementia, but it is unclear if this relationship is causal. This study investigated whether dementia associated with depression decreases with antidepressant use and is independent of the time between exposure to depression and the onset of dementia. We completed a 14-year longitudinal study of 4922 cognitively healthy men aged 71-89 years, and collected information about history of past depression, current depression and severity of depressive symptoms. Other measures included use of antidepressants, age, education, smoking and history of diabetes, hypertension, coronary heart disease, and stroke. The onset of dementia and death during follow-up was ascertained via the Western Australian Data Linkage System. A total of 682 men had past (n=388) or current (n=294) depression. During 8.9 years follow-up, 903 (18.3%) developed dementia and 1884 (38.3%) died free of dementia. The sub-hazard ratios (SHRs) of dementia for men with past and current depression were 1.3 (95% confidence interval (CI)=1.0, 1.6) and 1.5 (95% CI=1.2, 2.0). The use of antidepressants did not decrease this risk. Compared to men with no symptoms, the SHRs of dementia associated with questionable, mild-to-moderate and severe depressive symptoms were 1.2 (95% CI=1.0, 1.4), 1.7 (95% CI=1.4, 2.2) and 2.1 (95% CI=1.4, 3.2), respectively. The association between depression and dementia was only apparent during the initial 5 years of follow-up. Older men with history of depression are at increased risk of developing dementia, but depression is more likely to be a marker of incipient dementia than a truly modifiable risk factor.

Alcohol use, particularly alcohol abuse and dependence, are associated with increased risk of depression. Current diagnostic criteria suggest that the relationship is causal, but the evidence has only been derived from observational studies that are subject to confounding and bias. Given the logistic and ethical constraints that would be associated with a trial of alcohol use to prevent depression, we aimed to complete a Mendelian randomization study to determine if a genetic polymorphism associated with alcohol abuse and dependence (ADH1B rs1229984 G-->A) contributed to modulate the risk of depression in a community-derived cohort of older men. This retrospective analysis of a cohort of 3873 community-dwelling men aged 65-83 years living in the metropolitan region of Perth, Western Australia, investigated the triangular association between the rs1229984 G-->A polymorphism and alcohol use and, after 3.2-8.2 years, the presence of current depression or history of depression. The mean number of standard drinks consumed per week (n; standard deviation; range) according to genotype was AA 1.8 (17; 2.7; 0-7), GA 5.9 (262; 7.5; 0-35), GG 8.5 (3594; 10.9; 0-140) (GG>AA, GG>GA; P<0.001). Consumption of 1 or 2 drinks per day decreased the odds of depression (n=610) by 30 and 40%, whereas consumption of more than six drinks daily more than doubled the odds of depression (odds ratio: 2.12, 95% confidence interval: 1.02, 4.40). The ADH1B rs1229984 G-->A polymorphism was not associated with current or past depression (P=0.857). In addition, the presence of the A allele did not interact with the alcohol use to modulate the risk of depression (P=0.725). These results suggest that alcohol consumption does not cause or prevent depression in older men.

High total plasma homocysteine (tHcy) is associated with increased risk of cardiovascular events and depression. Consumption of B-vitamins (B6, B9 and B12) reduces tHcy by about 15%, but has equivocal effects on these health outcomes, suggesting that this relationship is either not causal or is confounded by other factors. The results of recent randomized trials suggest that antiplatelet therapy may confound these associations. This cross-sectional study assessed 3687 men aged 69-87 years for history of clinically significant depression (Geriatric Depression Scale 15 items 7) or a recorded diagnosis of depression in the Western Australian Data Linkage System, and collected information on the use of aspirin, B-vitamins and antidepressant medication, along with age, education, living arrangements, smoking history and medical comorbidity as assessed by the Charlson index. Participants donated a blood sample for the measurement of tHcy, and concentrations15 μmol l(-1) were considered high. Five hundred and thirteen (13.9%) men showed evidence of depression, and of those 31.4% had high tHcy, 41.5% were using aspirin, 6.8% were consuming B-vitamins. Multivariate logistic regression showed that high tHcy was associated with increased odds of depression (odds ratio (OR)=1.60, 95% confidence interval (CI)=1.20-2.14), as was the use of B-vitamins (OR=1.95, 95% CI=1.21-3.13). There was a significant interaction between high tHcy and aspirin use (OR=0.57, 95% CI=0.36-0.91), but not between high tHcy and B-vitamin use (OR=0.80, 95% CI=0.26-2.46). The analyses were adjusted for smoking status, Charlson index and use of antidepressants. The results of this study indicate that older men with high tHcy who use aspirin have lower risk of depression, and suggest that antiplatelet therapy may be an effective preventive or management strategy for these cases. Randomized trials are required to confirm the antidepressant effect of aspirin in people with high tHcy.

Aims/hypothesis: Cerebrovascular disease may be causal or a vulnerability factor in late-onset depression and may explain the high rate of depression in older adults with diabetes. We explored a wide range of potential explanatory variables of depression in a longitudinal study of older diabetic subjects to investigate the vascular depression hypothesis in these patients., Methods: We recruited 207 subjects with diabetes selected for potential cognitive deficits from an existing observational cohort study (average age 75.7 +/- 4.6 years, 52.2% men) for an assessment of depression using a standardised diagnostic instrument (Cambridge Examination for Mental Disorders of the Elderly -- Revised). All subjects underwent a detailed clinical assessment at baseline and at follow-up (after 7.5 +/- 1.1 years)., Results: Major depression was present in 45 subjects (21.7%) and minor depression in ten (4.8%). A positive history of strokes and the presence of peripheral arterial disease were significantly associated with depression at the time of diagnosis. In a subsample of 93 cases who underwent structural neuroimaging, the presence of cerebral infarcts was also significantly associated with depression. Treatment with glucose-lowering therapy, higher serum cholesterol levels and difficulties with activities of daily living at baseline were significant predictors of depression at follow-up., Conclusions/interpretation: A history of cerebrovascular disease was strongly associated with depression and cerebrovascular risk factors were significant predictors of depression in older diabetic patients. Our findings are consistent with the hypothesis that the excess risk of depression in older diabetic patients is related to underlying cerebrovascular disease.

The epsilon4 allele of apolipoprotein E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, amyloid beta1-40 (Abeta40) and homocysteine (Hcy) have all been correlated with the presence of dementia. Mutations in the methylnetetrahydrofolate reductase enzyme (MTHFR) have been associated with elevated levels of Hcy. This study explored the association of these factors with cognition and depression in community dwelling older men. Two hundred and ninety-nine men, mean age 78.9 years (SD 2.8), were studied in this cross-sectional survey. Mean plasma Hcy was 13.5 (SD 5.3) micromol/L. The MTHFR genotype had no obvious impact on Hcy levels. Ln Hcy and Ln Abeta40 were both inversely correlated with calculated glomerular filtration rate (cGFR), r = -0.41 (p < 0.001) and r = -0.28 (p < 0.001), respectively. There was a positive correlation between Ln Hcy and Ln Abeta40, r = 0.19 (p < 0.001), which remained significant after adjusting for cGFR, with a doubling of Hcy associated with a 24% increase of Abeta40. The e4 allele was associated with increased depressive symptoms as measured by the Geriatric Depression Scale-15, Odds ratio (OR) = 2.59 (95%CI 1.06-6.34) and poorer performance on the Clock Drawing Test, OR = 2.32 (95% CI: 1.25-4.29). There was a positive association between Abeta40 and Hcy, even after adjustment for cGFR in this sample of well, community dwelling older men. This association may help elucidate the link between elevated levels of Hcy and Alzheimer's disease.

Sex hormones have often been associated with changes in behavioural and mental abilities. This paper reviews the scientific literature published between 1990 and 2000 investigating the effects of oestrogen, testosterone and dehydroepiandrosterone (DHEA) on depression and dementia. Oestrogen seems to have a positive effect in preventing, but not treating, Alzheimer's disease. Oestrogen use may also improve mood amongst women with postnatal or perimenopausal depression; however, it may contribute to increasing depressive symptoms in women with premenstrual dysphoria. The behavioural effects of testosterone and DHEA remain unclear but the results of preliminary reports suggest that their use is associated with improved mood. At present, there is not enough hard data to support the use of sex hormones and DHEA for the treatment of depression or memory deficits.

This is a nonblind, case-controlled study comparing the risk of orthostatic hypotension (OH) in 2 groups of elderly depressed women: 22 normotensive and 21 hypertensive patients receiving thiazides. Blood pressure measurements and tilt-table tests produced similar results: increased drop in systolic blood pressure (SBP) after standing (p <0.001), with no significant differences between the groups (p = 0.523). There were no changes on diastolic blood pressure (DBP) after standing, or in SBP or DBP at rest. Dizziness was reported by 23 subjects (53.5%) before treatment, and by 16 subjects (38.1%) at week 8. Complaints of dizziness were not associated with OH (Kappa = 0.07).

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.