Neuropathological analysis of lacunes and microvascular lesions in late‐onset depression

M. Santos, G. Gold, E. Kövari, F. R. Herrmann, P. R. Hof, C. Bouras and P. Giannakopoulos (2010) Neuropathology and Applied Neurobiology 36, 661–672
Neuropathological analysis of lacunes and microvascular lesions in late‐onset depression Aims: Previous neuropathological studies documented that small vascular and microvascular pathology is associated with cognitive decline. More recently, we showed that thalamic and basal ganglia lacunes are associated with post‐stroke depression and may affect emotional regulation. The present study examines whether this is also the case for late‐onset depression. Methods: We performed a detailed analysis of small macrovascular and microvascular pathology in the post mortem brains of 38 patients with late‐onset major depression (LOD) and 29 healthy elderly controls. A clinical diagnosis of LOD was established while the subjects were alive using the DSM‐IV criteria. Additionally, we retrospectively reviewed all charts for the presence of clinical criteria of vascular depression. Neuropathological evaluation included bilateral semi‐quantitative assessment of lacunes, deep white matter and periventricular demyelination, cortical microinfarcts and both focal and diffuse gliosis. The association between vascular burden and LOD was investigated using Fisher's exact test and univariate and multivariate logistic regression models. Results: Neither the existence of lacunes nor the presence of microvascular ischaemic lesions was related to occurrence of LOD. Similarly, there was no relationship between vascular lesion scores and LOD. This was also the case within the subgroup of LOD patients fulfilling the clinical criteria for vascular depression. Conclusions: Our results challenge the vascular depression hypothesis by showing that neither deep white matter nor periventricular demyelination is associated with LOD. In conjunction with our previous observations in stroke patients, they also imply that the impact of lacunes on mood may be significant solely in the presence of acute brain compromise.     

Plasma BDNF and tPA are associated with late‐onset geriatric depression

Aims: Studies in the recent decade have shown that brain‐derived neurotrophic factor (BDNF) may play an important role in the pathogenesis of major depressive disorder (MDD). Tissue‐type plasminogen activator (tPA) has been implicated in the control of the direction of BDNF action. The aim of the study was therefore to investigate the changes of BDNF/tPA levels and their clinical meanings in geriatric depression. Methods: Plasma BDNF and tPA levels were measured in late‐onset geriatric depression (LGD) before treatment (n = 24) and after 6 weeks of antidepressant treatment (n = 24) compared with control subjects (n = 30) using enzyme‐linked immunosorbent assay. The severity of depression was assessed with the Hamilton Depression Rating Scale. Results: Baseline plasma BDNF and tPA levels were significantly lower in LGD patients compared to controls (P = 0.037 and P = 0.000, respectively). There was a heightening tendency of plasma BDNF level after treatment. Conclusions: Plasma BDNF and tPA levels are associated with LGD. The complex mechanism of BDNF and tPA in LGD should be further explored in future studies.     

Clinical profiles of late‐onset semantic dementia,compared with early‐onset semantic dementia and late‐onset Alzheimer's disease

Background: Semantic dementia (SD) has been recognized as a representative of dementia with presenile onset; however, recent epidemiological studies have shown that SD also occurs in the elderly. There have been few studies about the differences of clinical profiles between early‐onset SD (EO‐SD) and late‐onset SD (LO‐SD). Age‐associated changes in the brain might cause some additional cognitive and behavioural profiles of LO‐SD in contrast to the typical EO‐SD cases. The aim of the present study was to clarify the characteristics of neuropsychological, and behavioural and psychological symptoms of dementia (BPSD) profiles of LO‐SD patients observed in screening tests in comparison with EO‐SD patients and late‐onset Alzheimer's disease (LO‐AD) patients as controls. Methods: Study participants were LO‐SD (n = 10), EO‐SD (n = 15) and LO‐AD (n = 47). We examined the Mini‐Mental State Examination (MMSE), the Raven's Coloured Progressive Matrices (RCPM), the Short‐Memory Questionnaire (SMQ), the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI). Results: Both SD groups scored significantly lower than the LO‐AD patients in ‘naming’ of the MMSE. In the ‘construction’ score of the MMSE and the RCPM score, however, the LO‐SD patients as well as the LO‐AD patients were significantly lower than the EO‐SD patients. In the SMQ score, ‘euphoria’ and ‘disinhibition’ scores of the NPI, the SRI total and subscale scores, both SD groups were significantly higher, whereas in the ‘delusion’ score of the NPI, both SD groups were significantly lower than the LO‐AD patients. Conclusions: Visuospatial and constructive skills of LO‐SD patients might be mildly deteriorated compared with EO‐SD patients, whereas other cognitive and behavioural profiles of LO‐SD are similar to EO‐SD. Age‐associated changes in the brain should be considered when we diagnose SD in elderly patients.     

Is early‐onset clinically different from late‐onset frontotemporal dementia?

Background and purpose: Frontotemporal dementia (FTD) is the second most common neurodegenerative dementia in the young age after Alzheimer disease. Recent improvement in diagnostic assessment suggests that it is more common than previously, although with a great heterogeneity in clinical presentation. The different clinical patterns related to age of disease onset in behavioural variant FTD (bvFTD) have been fairly studied. Aim of the study was to evaluate whether age at disease onset modulate the heterogeneity of either cognitive impairment or behavioural disturbances in patients affected by bvFTD. Methods: One hundred and thirty‐four patients with bvFTD entered the study. Age at onset and demographic characteristics were carefully recorded. Each patient underwent a wide neuropsychological and behavioural standardized assessment, as well as a brain SPECT perfusion imaging study. Results: Behavioural variant FTD were subdivided into four groups according to the age at onset. The four quartile groups did not differ for demographic characteristics and family history for dementia. Global cognitive impairment as well as analysis of the different cognitive domains and behavioural patterns were comparable. Conclusions: These findings provide evidence that the clinical heterogeneity of bvFTD is not explained by age at disease onset. Further studies are needed.     

Atypical presentation of late‐onset Tay‐sachs disease

Introduction: Late‐onset Tay‐Sachs disease (LOTS) is a lysosomal storage disease caused by deficient Beta‐hexosaminidase A activity. Methods: We describe a 53‐year‐old woman who presented with adult‐onset leg weakness, and whose initial diagnosis was progressive muscular atrophy without identifiable etiology. Development of cerebellar ataxia in mid‐life prompted reassessment. Results: Beta‐hexosaminidase A quantification assay demonstrated absence of the isozyme. Genetic testing identified compound heterozygous mutations in the HEXA gene, confirming the diagnosis of LOTS. Conclusions: The phenotypic spectrum of LOTS includes motor neuronopathy, ataxia, choreoathetosis, neuropathy, and psychiatric symptoms in various combinations. This patient highlights the emergence of different clinical features over many years and emphasizes the need to consider LOTS in the differential diagnosis of progressive muscular atrophy. Muscle Nerve 49 : 768–771, 2014     

Reduced frontopolar activation during verbal fluency task associated with poor social functioning in late‐onset major depression: Multi‐channel near‐infrared spectroscopy study

Aim: Functional neuroimaging studies to date have indicated prefrontal dysfunction in late‐onset major depression (LOD). The relationships between prefrontal dysfunction and clinical characteristics including social functioning, however, have been unclear. The objective of the present study was to evaluate prefrontal hemodynamic response related to an executive task in LOD and to assess the relationship between activation in the prefrontal regions and clinical characteristics including social functioning. Methods: Twenty‐four subjects with LOD and 30 age‐ and gender‐matched healthy subjects were recruited for the present study. Hemoglobin concentration changes in the prefrontal and superior temporal cortical surface area were measured during verbal fluency task (VFT) using 52‐channel near‐infrared spectroscopy (NIRS), which enables real‐time monitoring of cerebral blood volume (CBV) in the cortical surface area. Results: The two groups had a distinct spatiotemporal pattern of oxy‐hemoglobin concentration change; LOD patients had less activation in a broad area covering both prefrontal and superior temporal cortices than healthy controls. In addition, reduced activation of the frontopolar region had a significant positive correlation with lower self‐assessment of social functioning scores in the patient group. Conclusion: Reduced frontopolar cortical activation was associated with social functioning impairment in patients with LOD, and NIRS may be an efficient clinical tool for monitoring these characteristics.     

Anxiety impairs depression remission in partial responders during extended treatment in late‐life

Objectives: More than half of older adults with major depressive disorder require extended treatment because of incomplete response during acute treatment. This study characterizes the effect of anxiety on remission during extended treatment for partial responders. Methods: Following 6 weeks of escitalopram 10 mg/day+depression care management (DCM), 124 partial responders (Hamilton Rating Scale for Depression (HRSD) scores of 11–14) were randomly assigned to receive extended treatment with escitalopram 20 mg/day+DCM with or without interpersonal psychotherapy (IPT) for 16 weekly sessions. Remission was defined as three consecutive weekly scores ≤7 on the HRSD. We assessed concurrent symptoms of anxiety using the Hamilton Rating Scale for Anxiety at pretreatment and after 6 weeks. We conducted Cox regression analysis of time to remission and logistic modeling of rates of remission. We also explored whether anxiety severity altered any impact of IPT. Results: Pretreatment anxiety was not associated with time to or rates of remission during 16 weeks of extended treatment. In contrast, more severe psychological symptoms of anxiety after 6 weeks of treatment was associated with both longer time to and lower rates of remission. However, there was no evidence that IPT showed any differential effects as a function of anxiety. Conclusions: In partial responders to 6 weeks of lower‐dose escitalopram and DCM, planning for extended treatment should account for psychological symptoms of anxiety. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.