Depressive Symptoms and Tau Accumulation in the Inferior Temporal Lobe and Entorhinal Cortex in Cognitively Normal Older Adults: A Pilot Study

Abstract

Background Depressive symptoms are common in older adults and associated with increased morbidity and cognitive decline. These symptoms occur during preclinical and prodromal stages of Alzheimer’s disease (AD), but their relationship to tau, one of the main AD proteinopathies, is poorly understood. Objective The objective of this study was to investigate the cross-sectional association between depressive symptoms and cerebral tau (18F T807 (a.k.a. 18F-AV-1451) tau positron emission tomography (PET) imaging) in cognitively normal (CN) older adults. Methods We measured depressive symptoms using the Geriatric Depression Scale (GDS), and in vivo cerebral tau using T807 PET in 111 CN older adults. We employed general linear regression models to evaluate the relationship of GDS score regressed on entorhinal cortex (EC) or inferior temporal (IT) tau in separate backward elimination models. Other predictors included age, sex, and in secondary analyses, amyloid (Pittsburgh Compound B (PiB) PET). Results Higher GDS was significantly associated with greater IT tau (partial r=0.188, p=0.050) and marginally associated with greater EC tau (partial r=0.183, p=0.055). In additional analyses including both linear and quadratic age terms, we found a significant u-shaped relation of GDS to age (p=0.001). Conclusions Results suggest that IT and EC tau are modestly associated with depressive symptoms in CN older adults. Findings suggest a link between depressive symptoms and tau mediated neurodegeneration in a region vulnerable in AD. Future longitudinal studies examining the association of more severe depressive symptoms and cerebral tau accumulation are needed to substantiate this finding and to guide prevention and treatment in AD.

Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild cognitive impairment

“…PET imaging studies have indicated that amyloid beta is globally increased across dementia subtypes, whereas tau has a distinct regional pattern of aggregation specific to each form of dementia . Of note, a recent PET imaging study reported that depressive symptomatology was linked to higher tau deposition in the inferior temporal lobe and entorhinal cortex . Further neuroimaging studies will be instrumental for assessing the regional impact of depressive symptomatology on tau accumulation.…”

“…37 Of note, a recent PET imaging study reported that depressive symptomatology was linked to higher tau deposition in the inferior temporal lobe and entorhinal cortex. 38 Further neuroimaging studies will be instrumental for assessing the regional impact of depressive symptomatology on tau accumulation.…”

Affective and emotional dysregulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria

“…Studies of subclinical depressive symptoms in CN older adults and across the AD spectrum have similarly shown associations with underlying structural and functional changes and more variably, with AD proteinopathies, A-beta and tau (Donovan et al , 2015; Babulal et al , 2016; Krell-Roesch et al , 2016; McCutcheon et al , 2016; Gatchel et al , 2017). Donovan and colleagues, in a cross-sectional study of CN older adults, found that subclinical depressive symptoms on the Geriatric depression scale (GDS) were associated with lower hippocampal volume, while GDS symptom clusters grouping with dysphoria, apathy, and anhedonia were associated with decreased hippocampal volume and reduced cerebral 18F-fluorodeoxyglucose (FDG) metabolism (for apathy-anhedonia symptoms); these associations were independent of cortical amyloid burden (Donovan et al , 2015).…”

The Relation Between Personality and Biomarkers in Sensitivity and Conversion to Alzheimer-Type Dementia

“…For example, Schultz et al (2019) recently reported a relationship between neuroticism and regional tau deposition using positron emission tomography in a smaller cross-sectional sample (N = 128) of cognitively normal older adults. Similarly, Gatchel et al (2017) reported an association between depressive symptoms and tau deposition in a cognitively normal sample and Terracciano et al (2013) reported an association between neuroticism and more advanced staging of neurofibrillary tangles in an autopsy study. Finally, as noted above, we have emphasized the earliest stages of AD, i.e., cognitively normal vs very mildly demented individuals.…”