Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment

Abstract

Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer’s disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe 18F-florbetapir (AV-45). 18F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia.

Lack of a Role for Alzheimer’s Disease Pathology in Late-Life Depression, or Just No Relationship With Amyloid?

“…This is highlighted by the study’s secondary analyses, where there was no difference in amyloid binding observed between early-onset and late-onset depressed subjects (1). Supporting these findings, some previous studies in both cognitively impaired and cognitively intact older adults have similarly failed to associate amyloid burden with depressive symptoms (7; 8). Even more compellingly, a large longitudinal neuropathological study found that the occurrence of depression was not related to a specific underlying neuropathology, and the effect of depressive symptoms on cognitive decline was unrelated to and independent of underlying neuropathology (9).…”

Benzodiazepine Use Attenuates Cortical β-Amyloid and is Not Associated with Progressive Cognitive Decline in Nondemented Elderly Adults: A Pilot Study Using F18-Florbetapir Positron Emission Tomography

“…Lastly, cortical Aβ accumulation is an early-occurring pathological change, whose rate of deposition slows down over the course of the disease in elderly individuals (40). As a result, we may not have observed drastic changes in cortical Aβ levels over the 2 years of follow-up in both the CON+BZD and CON-BZD groups.…”

Depressive and anxiety symptoms and cortical amyloid deposition among cognitively normal elderly persons: the Mayo Clinic Study of Aging

“…Moreover, the amount of deposited amyloid correlated with the rate of progression in depressed individuals (Brendel et al , 2015). In contrast to studies that reported a relationship between neuropsychiatric symptoms and amyloid deposition, a study among patients with MCI and AD failed to detect an association between cortical amyloid deposition and depressive symptoms (Chung et al , 2016). Our findings may be pertinent to the recently reported construct of Mild Behavioral Impairment (MBI) which is defined as a change in behavior or personality in non-demented persons aged 50 years and older (Ismail et al , 2016).…”