Cortical changes associated with depression and antidepressant use in Alzheimer and Lewy body dementia: an MRI surface-based morphometric study.

CONTEXT: Depression is common in dementia, especially in the early stages, with important clinical implications, but the etiology is unknown and most likely heterogeneous. Antidepressant use in the elderly without dementia has previously been shown to be associated with high risks of adverse events and with structural brain alterations. OBJECTIVE: To investigate cortical changes associated with depression and antidepressant use in patients with mild Alzheimer's disease (AD) and Lewy body dementia (LBD). METHODS: 74 subjects with mild AD and LBD from geriatric and psychiatry outpatient clinics in Western Norway were included. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depression. Automatic preprocessing using Freesurfer included steps for white and grey matter surface reconstruction. The resulting cortical thickness was analyzed using linear modeling. RESULTS: Clusters of depression-associated thinning were found in prefrontal and temporal areas. Treatment-associated thinning was observed in the parahippocampal region and was significant even after correction for age, sex, AD/LBD diagnosis, and MADRS scores. CONCLUSION: Depression in mild AD and LBD is associated with cortical thinning in prefrontal and temporal areas. The findings suggest that depressive symptoms in mild dementia could develop due to neurodegeneration in the same neural circuits that are critical for depression across different brain disorders. Antidepressant use in patients with mild AD and LBD is associated with parahippocampal thinning. Taken together with low efficacy of antidepressants in cognitively impaired patients and high risks of adverse events, our results suggest a need to re-evaluate the treatment approaches for depression and the role of antidepressants in patients with dementia.

White matter hyperintensities and the course of depressive symptoms in elderly people with mild dementia.

OBJECTIVES: To explore the relationship between white matter hyperintensities (WMH) and the prevalence and course of depressive symptoms in mild Alzheimer's disease (AD) and Lewy body dementia. DESIGN: This is a prospective cohort study conducted in secondary care outpatient clinics in western Norway. SUBJECTS: The study population consisted of 77 elderly people with mild dementia diagnosed according to standardised criteria. METHODS: Structured clinical interviews and physical, neurological, psychiatric, and neuropsychological examinations were performed and routine blood tests were taken. Depression was assessed using the depression subitem of the Neuropsychiatric Inventory and the Montgomery-Åsberg Depression Rating Scale (MADRS). A standardised protocol for magnetic resonance imaging scan was used, and the volumes of WMH were quantified using an automated method, followed by manual editing. RESULTS: The volumes of total and frontal deep WMH were significantly and positively correlated with baseline severity of depressive symptoms, and depressed patients had significantly higher volumes of total and frontal deep WMH than non-depressed patients. Higher volumes of WMH were also associated with having a high MADRS score and incident and persistent depression at follow-up. After adjustment for potential confounders, frontal deep WMH, in addition to prior depression and non-AD dementia, were still significantly associated with baseline depressive symptoms (p = 0.015, OR 3.703, 95% CI 1.294-10.593). Similar results emerged for total WMH. CONCLUSION: In elderly people with mild dementia, volumes of WMH, in particular frontal deep WMH, were positively correlated with baseline severity of depressive symptoms, and seemed to be associated with persistent and incident depression at follow-up. Further studies of the mechanisms that determine the course of depression in mild dementia are needed.

Depressive symptoms in Alzheimer's disease and lewy body dementia: a one-year follow-up study.

OBJECTIVE: To explore the course of depression in people with mild dementia and identify predictors for depression at 1-year follow-up. METHODS: Patients with mild dementia (n = 199) were assessed using Montgomery and Åsberg Depression Rating Scale (MADRS) and the depression item from Neuropsychiatric Inventory (NPI) at baseline and after 1 year. A score above 6 on MADRS indicates at least mild depression. Linear and logistic regression analyses were performed to identify predictors of change in depression scores. RESULTS: Among subjects with depression at baseline, 68.1% remained depressed at follow-up, whereas 31.9% had remitted, based on MADRS. Among patients without depression at baseline, 77.1% remained non-depressed at follow-up, whereas 22.9% had incident depression. The proportion with persistent depression was higher in the combined dementia with Lewy bodies (DLB)/Parkinson's disease with dementia (PDD) group (45.5%) compared to AD (28%) (p < 0.05). Greater decline on the Mini Mental State Examination (p < 0.001) and higher baseline MADRS score (p < 0.001) were significant predictors of increased MADRS score. CONCLUSION: Two thirds of patients with depression at baseline were still depressed at follow-up, more so in DLB with PDD compared to AD. Cognitive decline was associated with worsening of depressive symptoms.

Depression in mild dementia: associations with diagnosis, APOE genotype and clinical features.

BACKGROUND: Depression is common in dementia, with important clinical implications. Few studies of depression in dementia with Lewy bodies are available, and the results are inconsistent. OBJECTIVE: To examine the frequency of depression and its characteristics and correlates, in people with mild dementia. METHODS: All referrals for patients with a first time diagnosis of dementia to geriatric and older psychiatry outpatient clinics in the counties of Rogaland and Hordaland in Western Norway from March 2005 to March 2007 were screened for the study. Participants and their caregivers underwent a comprehensive and standardised diagnostic and assessment procedure. The depression subitem of the neuropsychiatric inventory (NPId) and Montgomery and Åsberg depression rating scale (MADRS) were used to estimate depression. Cut-off scores for any depression were 0/1 (NPId) and 6/7 (MADRS), and for clinically significant depression 3/4 and 14/15, respectively. RESULTS: Two hundered and twenty-three subjects with dementia participated, of whom 59 and 50% showed symptoms of depression assessed by NPI or MADRS, respectively, and 25 and 16% had clinically significant depression as measured by NPI and MADRS, respectively. Depression was more frequent in dementia with Lewy bodies (DLB) than in Alzheimer's disease (AD; p < 0.05). APOE genotype was available in 153 patients, and in AD, but not in DLB, a general linear model showed that the presence of APOEε4 allele was significantly associated with depression (F = 4.14; p = 0.045). CONCLUSION: Depression is common even in mild dementia, and more common and severe in DLB compared to AD. Future studies should explore the longitudinal course of depression in DLB, and the neural underpinnings of depression in DLB.

[The concept of hyperthymia]. / Zum Konzept der Hyperthymie - Historische Entwicklung und aktuelle Aspekte -

The article reviews the conceptual history of "hyperthymia". Since K. W. Stark had used this term in the early 19(th) century, it has developed in two different directions: (1) to delineate a psychopathological syndrome and (2) to define a type of personality disorder (psychopathy). As Kurt Schneider's personality disorder (psychopathy) concept was easily understood and highly practicable, it became influential during the 20(th) century. Earlier before, psychiatrists such as E. Mendel, C. Wernicke and C. G. Jung had described entities such as "chronic mania", "hypomania" or "sanguinic degeneration", which were rather similar to each other. We analyze the historical development of such concepts. Emil Kraepelin was highly influential, as he introduced "constitutional excitation" into a broad concept of manic-depressive illness and saw it as a very mild form. After Kraepelin such spectrum concept was first forgotten. Only in recent years these historical considerations were confirmed by empirical observations, although a separate hyperthymic disorder is neither part of DSM-IV nor ICD-10. The concept of a hyperthymic temperament or a hyperthymic personality is a trait-marker and should be differentiated from hypomania as a state-marker. Nowadays, the importance of hyperthymia is not so much one of a disorder requiring treatment; rather the concept has interesting genetic, diagnostic and conceptual consequences.