-
[show abstract]
[hide abstract]
ABSTRACT: To assess glial and neuronal density and neuronal volume in two areas of the caudate nucleus in late-life major depression.
A postmortem study using the disector and nucleator methods to estimate neuronal density and volume and glial density of cells from human brain tissue from the anterior portion (dorsolateral and ventromedial aspects) of the caudate nucleus.
Brain tissues were obtained from the Newcastle Brain Tissue Resource at Newcastle University, UK.
The study group consisted of 13 subjects with late-life major depression and nine comparison subjects of similar age.
Evidence of moderate reductions in neuronal density was found in the depressed group in both the dorsolateral and ventromedial areas of the caudate nucleus. There were no significant changes in glial density or neuronal volume in either area nor was there any evidence of differences in depression in early and late-onset subgroups.
Neuroimaging abnormalities in frontal and subcortical areas including ischemic hyperintensities and a reduction in volume and metabolism in the caudate nucleus have been reported in late-life depression, and previous morphometric studies have reported neuronal changes in prefrontal cortical areas. The findings in this study extend these morphometric investigations in late-life depression to the caudate nucleus, suggesting that neuronal abnormalities are present in this subcortical nucleus as well as in these related prefrontal areas.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 02/2011; 19(2):132-41. · 3.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The orbitofrontal cortex has been implicated as a key component in depression by several imaging studies. This study aims to examine morphometrically glial cell and neuronal density and neuronal volume in the orbitofrontal cortex of late-life major depression patients.
Post mortem tissue from 13 patients with major depression and 11 matched controls was obtained and analyzed using the optical disector and nucleator methods.
No changes were found in glial cell, pyramidal or non-pyramidal neuron density, or in non-pyramidal and pyramidal neuron volume in the orbitofrontal cortex.
Based on previous findings, this study suggests variability in morphological changes within the orbitofrontal cortex, as well as the prefrontal cortex as a whole.
International Psychogeriatrics 02/2011; 23(1):132-40. · 2.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Late-life depression has been associated with cerebrovascular disease and especially with ischaemic white matter hyperintensities on magnetic resonance imaging. Neuroimaging and morphometric studies have identified abnormalities in the dorsolateral prefrontal cortex.
To examine glial and neuronal density and neuronal volume in the dorsolateral prefrontal cortex in late-life major depression.
We used the disector and nucleator methods to estimate neuronal density and volume and glial density of cells in the dorsolateral prefrontal cortex in a post-mortem study of 17 individuals with late-life major depression and 10 age-matched controls.
We found a reduction in the volume of pyramidal neurones in the whole cortex, which was also present in layer 3 and more markedly in layer 5. There were no comparable changes in non-pyramidal neurones and no glial differences.
Overall, we found a decrease in pyramidal neuronal size in the dorsolateral prefrontal cortex in late-life depression.
The British journal of psychiatry: the journal of mental science 09/2009; 195(2):163-9. · 6.62 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To examine the relationship of the anatomic distribution of amyloid deposition to focal and global cognitive dysfunction in different subtypes of dementia.
We quantified AB40 and AB42 in the temporal lobe and entorhinal cortex and examined their relationship to cognitive functions in Alzheimer's disease (AD), vascular dementia (VaD) and dementia with Lewy bodies (DLB).
We found a correlation between memory impairment, but not global cognitive impairment, and amyloid load in these areas in AD and VaD but not in DLB. This relationship was stronger for AB42 and in the entorhinal cortex.
The anatomic location of amyloid deposition is an important factor-specific factor in memory impairment in AD and VaD.
Dementia and Geriatric Cognitive Disorders 02/2005; 19(2-3):57-60. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cerebrovascular amyloidosis occurs increasingly in older age. The amyloid β (Aβ) protein type of cerebral amyloid angiopathy (CAA) is the most common form of this microangiopathy, evident in virtually all cases of Alzheimer's disease (AD). CAA may range from focal deposits to widespread infiltration of amyloid in walls of perforating and meningeal arteries, capillaries and diffuse perivascular plaques. Prior to their degeneration vascular smooth muscle cells may be sensitised and stimulated by the aggregated amyloid peptide itself and cytokines. Two patterns of CAA namely arteriolar and capillary types have recently been recognized. CAA also occurs in other dementing conditions including Down's syndrome and dementia with Lewy bodies. It is the principal feature of the hereditary amyloid angiopathies such as hereditary cerberal haemorrhage with amyloidosis of the Dutch type and familial British dementia. Varying degrees of CAA have been recorded in early onset familial AD. Mutations in the amyloid precursor protein (APP) gene that lie in codons within the Aβ domain may result in a phenotype characterised by severe CAA, cerebral infarction and white matter disease. The apolipoprotein E ε4 allele is a strong factor in the development of Aβ CAA, which may progress to lobar or intracerebral hemorrhages. At least two different transgenic mice models over-expressing human APP implicate neuronal origin of the Aβ within vascular deposits. CAA may largely develop due to lack of clearance by reduced proteolytic degradation and progressive blockage of the interstitial drainage pathways via the brain vascular routes superimposed by age-related arteriosclerotic changes. Current observations from both sporadic and familial cases suggest CAA to be an independent factor for cognitive impairment and dementia.
Current Medicinal Chemistry - Immunology Endocrine & Metabolic Agents 11/2003; 3(4):317-327.
-
[show abstract]
[hide abstract]
ABSTRACT: Signal hyperintensities on magnetic resonance imaging in late-life depression are associated with treatment resistance and poor outcome. These lesions are probably vascular in origin and proposed sites for vascular damage include the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC).
We therefore examined white matter in these areas for microvascular disease and evidence of ischemia using intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). We obtained postmortem tissue from elderly depressed (n = 20) and control (n = 20) subjects and blindly rated microvascular disease and ICAM-1 and VCAM-1 amount using quantitative image analysis in sections of the DLPFC, ACC and occipital cortex (OC; control area).
We found a significant increase in ICAM-1 in the deep white matter of the DLPFC in the depressed group (p = 0.01) and a trend towards an increase for VCAM-1 (p = 0.10). In the gyral white matter there was a trend towards significance for both molecules (p = 0.07 and 0.10). No differences were found in the ACC or OC or for microvascular disease in any area.
These findings are consistent with white matter ischemia in the DLPFC and lend support to the 'vascular depression' hypothesis. They implicate the DLPFC as an important site in the pathogenesis of late-life depression and have major implications for the understanding and management of late-life depression and raise the possibility of novel treatments being introduced in the future.
International Journal of Geriatric Psychiatry 02/2003; 18(1):7-13. · 2.42 Impact Factor
