Lower regional gray matter volume in the absence of higher cortical amyloid burden in late-life depression

Abstract

Late-life depression (LLD) is associated with a risk of developing Alzheimer's disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [18F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1±7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4±6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GM driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder.

What Can We Tell About the Effect of Electroconvulsive Therapy on the Human Hippocampus?

“…Late-life depression is associated with an increased risk of developing dementia, 92 suggesting shared neurobiology with dementia, although higher amyloid accumulation was not identified in a large cohort of patients with latelife depression. [93][94][95] Late-life depression is also associated with microvascular dysfunction, 96 as suggested by the vascular depression hypothesis. 97 Although ECT was also effective in older depressed patients with age-related brain pathology, including hippocampal atrophy, white matter hyperintensities, and amyloid accumulation, 98 the above-mentioned age-related matters might affect longitudinal ECT-related brain changes and their association with clinical changes.…”

Plasma Amyloid-β dynamics in late-life major depression: a longitudinal study

“…In AD, numerous studies have shown a reduction in both the plasma and CSF Aβ42/Aβ40 ratio which has been associated with increases in amyloid PET uptake [16,17]. Studies of PET amyloid scans in MDD have provided conflicting results with some reports of increased amyloid build up [14,[18][19][20][21], or no change [22,23], and most surprisingly even reductions in amyloid compared to controls as well [24]. The basis for these conflicting PET findings may be due to methodological differences across studies.…”

Towards Defining the Neuroanatomical Basis of Late-Onset Psychiatric Symptoms

“…1 As an example, late-life depression (onset after age 65) has been investigated more than any other late-life psychiatric syndrome. Multiple studies suggest that late-life depression and dementia share common neuropathological changes, including reduced gray matter volume 2 and hippocampal atrophy. 3 Interestingly, some of these changes, such as hippocampal atrophy, are associated specifically with late-onset depression and not depression that begins earlier in life.…”