Neuropathological correlates of late-life depression in older people

Abstract

BackgroundDepression is common in old age and is associated with risk of dementia, but its neuropathological correlates in the community are unknown.AimsTo investigate for the first time in a population-representative sample of people with no dementia the association between depression observed during life and neurofibrillary tangles, diffuse and neuritic plaques, Lewy bodies, brain atrophy and cerebrovascular disease found in the brain at post-mortem.MethodOut of 456 donations to a population-based study, 153 brains were selected where donors had no dementia measured in life. Alzheimer and vascular pathology measures, Lewy bodies and neuronal loss were compared between those with (n = 36) and without (n = 117) depression ascertained using a fully structured diagnostic interview during life. Brain areas examined included frontal, parietal, temporal and occipital cortical areas as well as the entorhinal cortex, hippocampus and brain-stem monoaminergic nuclei.ResultsDepression was significantly associated with the presence of subcortical Lewy bodies. No association was found between depression and cerebrovascular or Alzheimer pathology in cortical or subcortical areas, although depression was associated with neuronal loss in the hippocampus as well as in some of the subcortical structures investigated (nucleus basalis, substantia nigra, raphe nucleus).ConclusionsLate-life depression was associated with subcortical and hippocampal neuronal loss but not with cerebrovascular or Alzheimer pathology.

Association of chronic divalproex sodium use and brain atrophy in Alzheimer’s disease

“…We cannot completely exclude the possibility of underlying influences of comorbid late-life depression on brain atrophy and cognitive impairment, since late-life depression was associated with significant and direct subcortical and hippocampal neuronal loss and cognition, which may have substantially impacted on the study results [16,17]. Other pharmacological factors (e.g., antihypertensive medications and alcohol) should also be kept in mind because these are also known to cause substantial and independent decline in cognitive function and brain volumes [18].…”

[IC‐P‐095]: MICROBLEEDS ARE ASSOCIATED WITH DEPRESSIVE SYMPTOMS IN ALZHEIMER's DISEASE

“…An autopsy study in older people with late-life depression, however, found that depression was not related to WMHs or lacunes [31]. In a population-based study in which depression was diagnosed by a structured diagnostic interview, depression was associated with the presence of Lewy bodies, but not with the presence of WMHs and/or lacunes or Alzheimer pathology [32]. These (5) 33 (4) 43 (8) 36 (4) 2 lacunes 28 (1) 5 (1) 12 (2) 11 (1) 3 lacunes 52 (2) 10 (1) 28 (5) 14 (1 (16) 34 (4) 63 (12) c 256 (30) c,d…”

Pontine Microbleeds and Depression in Stroke

“…[27][28][29] Also, structural disruptions in the brainstem raphe have consistently been found in depression 30,31 together with neuronal loss in the same region. 32 Small lesions, in the form of CMBs, in this area could therefore cause depletion of the ascending serotonergic system to the forebrain and depression.…”