Late-life depression is not associated with dementia-related pathology.

Abstract

Objective To test the hypothesis that late-life depression is associated with dementia related pathology. Method Older participants (n=1,965) in 3 longitudinal clinical-pathologic cohort studies who had no cognitive impairment at baseline underwent annual clinical evaluations for a mean of 8.0 years (SD = 5.0). We defined depression diagnostically, as major depression during the study period, and psychometrically, as elevated depressive symptoms during the study period, and established their relation to cognitive outcomes (incident dementia, rate of cognitive decline). A total of 657 participants died and underwent a uniform neuropathologic examination. We estimated the association of depression with 6 dementia related markers (tau tangles, beta-amyloid plaques, Lewy bodies, hippocampal sclerosis, gross and microscopic infarcts) in logistic regression models. Results In the full cohort, 9.4% were diagnosed with major depression and 8.6% had chronically elevated depressive symptoms, both of which were related to adverse cognitive outcomes. In the 657 persons who died and had a neuropathologic examination, higher beta-amyloid plaque burden was associated with higher likelihood of major depression (present in 11.0%; odds ratio = 1.392, 95% confidence interval = 1.088, 1.780) but not with elevated depressive symptoms (present in 11.3%; odds ratio = 0.919, 95% confidence interval = 0.726, 1.165). None of the other pathologic markers was related to either of the depression measures. Neither dementia nor antidepressant medication modified the relation of pathology to depression. Conclusion The results do not support the hypothesis that major depression is associated with dementia related pathology.

Association of Obstructive Sleep Apnea with Episodic Memory and Cerebral Microvascular Pathology: A Preliminary Study

“…17 Whether depression shares common pathologic mechanisms with AD-related pathology remains controversial. 18,19 On the other hand, a large body of imaging research has demonstrated the vascular and neural bases for these disorders. While OSA is known for its destructive nature in the cerebral vascular and neural systems, whether OSA plays an important role in the cognitive deteriorating process in older adults with amnestic MCI (aMCI) and depression is not clear.…”

Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia

“…Late-life depression is associated with an increased risk for dementia with an odds ratio of 1.85 according to meta-analyses of 23 prospective studies including more than 49,600 participants (1,2). Notably, depression has been shown to be associated with faster decline of cognitive performance and with the clinical diagnosis of dementia but not with the traditional dementia pathologies such as beta-amyloid plaques, tau tangles, Lewy bodies, hippocampal sclerosis, microinfarcts, and macroinfarcts (3)(4)(5)(6). How depression and its associated molecular changes act to increase dementia risk is not well understood and is the focus of this work.…”

Eu/Us/Ctad Task Force: Lessons Learned From Recent and Current Alzheimer’s Prevention Trials

“…Multiple studies have demonstrated an association between neuropsychiatric symptoms and an increased risk of dementia and AD (41–44), although the mechanisms underlying this association remain unclear. While some studies have suggested that depression is associated with an increase in accumulation of brain amyloid, neurofibrillary tangles, or hippocampal atrophy (45–47), others have shown no association between dementia-related markers of pathology and depression (48). Anxiety has also been linked to increased levels of plaques and tangles (46).…”