Thea J. Heeren

Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression

Background: Reduced hippocampal volume and increased prevalence of subcortical white matter lesions are associated with both recurrent early onset depression (EOD) and late onset depression (LOD). It is not clear whether these two factors differentially affect the age of onset of first depression. Therefore, we wished to investigate the relationship between age of first depression onset and hippocampal volume, with adjustment for subcortical white matter lesions. Methods: MRI brain scans were used to compare hippocampal volumes and white matter lesions between age matched female patients (>60 years) with recurrent EOD and LOD and healthy controls. Results: When comparing the three groups and adjusting for age, the Mini-Mental State Examination score, total brain volume and total hippocampal volume were significantly smaller in patients with EOD compared with controls (5.6 vs 6.1 ml; p = 0.04). The prevalence of larger subcortical white matter lesions was higher in patients with LOD compared with patients with EOD (47% vs 8%; p = 0.002). Patients with LOD did not differ in hippocampal volume from patients with EOD or from controls. Conclusions: In late life depression, age of first depression onset may distinguish between different independent neuropathological mechanisms. A small hippocampus volume may be a neuranatomical marker of EOD depression and larger subcortical white matter lesions could be an intermediate between cerebrovascular disease and LOD.

Hippocampal changes and white matter lesions in early-onset depression

BACKGROUND Hippocampal volume reduction and increased prevalence of subcortical white matter lesions have been reported in late-life depression. We aimed to examine whether total number of subcortical white matter lesions were associated with reduced hippocampal volume in aged female subjects with early-onset depression (< 45 years) and healthy comparison subjects. METHODS The study included 28 middle-aged and elderly subjects with major depression and 41 age-matched control subjects. Hippocampal, parahippocampal gyrus, and orbitofrontal cortex volumes were determined using manual tracing methods. White matter lesions were rated from T2-weighted MRI scans using a semiquantitative classification scale. RESULTS After controlling for total brain volume and age, patients had reduced hippocampal volume due to right hippocampal volume decrease (2.84 mL vs. 3.12 mL, F = 16.6, p < .001). Parahippocampal and orbitofrontal volumes did not differ significantly between groups. Multiple linear regression analysis indicated that reduced hippocampal volume did not significantly correlate with total number of subcortical white matter lesions (t = .673, p = .518). CONCLUSIONS Right hippocampal volume was reduced in aged female early-onset subjects with depression. Total number of subcortical white matter lesions was not associated with the decrease in right hippocampal volume. Our data suggest hippocampal involvement, independent of subcortical white matter lesions, in the neuropathology of early-onset depression.

Prevalence of Dementia in the ‘Oldest Old’ of a Dutch Community

To estimate the prevalence rate of dementia in subjects 85 years of age and over.

Efficacy of treatment in older depressed patients : A systematic review and meta-analysis of double-blind randomized controlled trials with antidepressants

BACKGROUND This systematic review evaluated all published double-blind, randomized controlled antidepressant trials (RCTs) of acute phase treatment of older depressed patients. METHODS Meta-analyses were conducted in 51 double-blind RCTs of antidepressants in older patients. The results were also compared with 29 double-blind RCTs that did not produce extractable data to enter the meta-analysis. RESULTS All classes of antidepressant (TCAs, SSRIs and other antidepressants) were more effective than placebo in achieving response. In achieving remission however, only pooling all 3 classes of antidepressants together showed a statistically significant difference from placebo. No differences were found in remission or response rates between classes of antidepressants. TCAs were also equally effective compared with SSRIs in achieving response in more severely depressed patients. The numbers needed to treat (NNT) were 14.4 (95% CI 8.3-50) for one additional remission to antidepressants compared with placebo and 6.7 (95% CI 4.8-10) for response. The results of the double-blind RCTs that did not produce extractable data to enter the meta-analysis were in concordance with the RCTs that were included in the meta-analysis. LIMITATIONS Only 4 RCTs were found that have not been published. Few studies have focused on severely depressed older people. CONCLUSIONS Antidepressant treatment in older depressed patients is efficacious. We could not demonstrate differences in effectiveness between different classes of antidepressants; this was also the case in more severely depressed patients.

Effects of recurrent major depressive disorder on behavior and cognitive function in female depressed patients

Little is known about the effects of recurring depressive episodes on cognition and behavior. The objective of the study was to compare cognitive function and depression-related behavior between healthy female subjects and female outpatients with early-onset DSM-IV recurrent major depressive disorder and to investigate the effect of cumulative depressive duration. Neuropsychological tests and scales for apathy, anhedonia and psychomotor retardation were assessed in 23 female patients and 60 healthy age-matched female controls. Significantly higher levels of apathy, anhedonia and psychomotor retardation, and worse performance on tests of executive function were found in the patient group compared with the healthy controls. In the patient group, cumulative depression duration was not significantly correlated with cognitive function, apathy, anhedonia or psychomotor retardation. The deficits in executive function were not related to the actual level of depression. Mild executive dysfunction may be the effect of the illness process underlying recurrent depressive disorder. Repeated or extensive depressive episodes do not seem to additionally affect cognitive deficits or behavior in depressed patients.

Apathy, Anhedonia, and Psychomotor Retardation in Elderly Psychiatric Patients and Healthy Elderly Individuals

Normal aging of the brain affects the basal ganglia-thalamocortical circuits. These circuits are implicated in sev eral neuropsychiatric disorders. Normal aging may therefore influence the symptomatology of psychiatric disorders in the elderly. We investigated motivational behavior that is associated with the function of these circuits, such as apathy, anhedonia, and psychomotor retardation in healthy elderly subjects and psychiatric inpatients (age ≥ 60 yr). Apathy, anhedonia, and psychomotor retardation were assessed with the Apathy Evaluation Scale, the Snaith- Hamilton Pleasure Scale, and the Widlöcher Retardation Rating Scale. Other measurements included the Comprehensive Psychopathological Rating Scale, the Mini-Mental State Examination, and the assessment of vas cular risk factors. We found some evidence for age-related changes in motivational behavior. In the healthy elderly group (n = 64), increasing age was associated with anhedonia, and in the patient group (n = 62), increasing age was associated with psychomotor retardation. Motivational disturbances could be the effect of an interaction between brain aging and the neuropathology of psychiatric disorders in the elderly. (J Geriatr Psychiatry Neurol 2001; 14:11-16).

Is apathy in late-life depressive illness related to age-at-onset, cognitive function or vascular risk?

BACKGROUND Apathy has been shown to be an important feature of degenerative, vascular or traumatic brain disorder. Its presence is associated with high depression scores, higher age, low performance on frontal tasks, and more severe deep white matter hyperintensities. In late-life depression, lack of interest or motivation are often more prominent than depressed mood, especially in the late-onset type. It was hypothesized that in a heterogeneous sample of elderly depressed patients, apathy is associated with late-onset type of depression, cognitive dysfunction or vascular risk factors. METHOD The Apathy Evaluation Scale (AES) was administered to twenty-nine elderly (> or = 60 years) inpatients with a DSM-IV major depression or dysthymic disorder. The severity of the depression was measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and cognitive function with the Mini-mental State Examination (MMSE). The presence of vascular risk factors was traced in the patients medical records. RESULTS Apathy was found in 86% of the patients. The AES-score was correlated with the negative symptom score, but not with total MADRS or MMSE-score. No difference in AES-score between early-onset depressed (n = 16) and late-onset depressed (n = 13) patients was found, and between patients with or without vascular risk. CONCLUSION Apathy is a main feature of moderate to severe depressive illness in elderly patients and related to the negative symptoms of the disorder. Further studies should include less severely depressed patients and investigate the relation between depression severity and apathy.

Odor discrimination in patients with frontal lobe damage and Korsakoff's syndrome.

The involvement of the frontal cortex and thalamic nucleus in odor discrimination in humans was assessed. Six patients with frontal lobe brain damage, seven patients with alcoholic Korsakoffs syndrome and 16 healthy comparison subjects completed odor detection and odor discrimination tasks. Multivariate general linear modeling with age as a covariant revealed significantly decreased odor discrimination ability in frontal lobe damaged patients and marginally decreased odor discrimination ability in Korsakoffs syndrome patients as compared to the healthy comparison subjects. No deficits were found in odor detection ability. The findings suggest that in human odor discrimination, there is more involvement of cortico-cortical pathways than of thalamo-cortical pathways.

Depressogenic medication as an aetiological factor in major depression: an analysis in a clinical population of depressed elderly people

To study the role of depressogenic medication in the aetiology of major depression in the elderly.

Early response as predictor of final remission in elderly depressed patients

Several studies have attempted to predict the final response or remission based on improvement during the early course of treatment of major depression. There is however a great variation in cut offs used to define early response and in the optimal week to predict final results.