Relationship between neuropsychiatric symptoms and Alzheimer's disease pathology: An in vivo positron emission tomography study

Abstract

Objectives To investigate the relationship between amyloid‐β‐ and tau‐based Alzheimer's disease (AD) pathologies assessed using positron emission tomography imaging and neuropsychiatric symptoms (NPS) in a sample of AD continuum including clinically normal subjects and patients with mild cognitive impairment or AD. Methods We analyzed datasets of the Alzheimer's disease Neuroimaging Initiative and included amyloid‐positive subjects who underwent an AV‐45 scan within 1 year of an AV‐1451 scan (n = 99). Correlation between standardized uptake value ratio (SUVR) of AV‐45 and AV‐1451 and the Neuropsychiatric Inventory (NPI) score (and its four domain subscores for hyperactivity, psychosis, affective, and apathy) was evaluated. Stepwise logistic regression analysis was used to examine the influence of SUVRs on the presence of NPS. SUVRs were also tested for their ability to discriminate the group with NPS using receiver operating characteristic (ROC) curve analyses. Results Significant positive relationships were found between the total NPI score and affective symptoms and Braak 1&2 (transentorhinal region) AV‐1451 SUVR. Stepwise logistic regression analysis identified tau accumulation in the area of Braak 1&2 as a significant covariate discriminating the presence of affective symptoms. The area under the ROC curve analysis showed that subjects with affective symptoms were discriminated by AV‐1451 SUVR with an accuracy of 77.7%. Conclusions Tau aggregation in the transentorhinal region, where neurodegeneration affected by tau pathology was seen in the early stage of AD, correlated with more severe NPS, especially affective symptoms. Therefore, tau pathology in the transentorhinal cortex might be associated with affective symptoms in the early stage of AD.

Neuropathology of patients with preclinical or early clinical Alzheimer's disease with pathogenic PSEN1_p. L392V: Comparison of advanced siblings

“…[15][16][17] Yasuno et al showed that emotional dysregulation because of the Aβ pathology in the precuneus/posterior cingulate cortex may be related to depression symptoms, 18 and they additionally showed tau aggregation in the transentorhinal region by using positron emission tomography (PET), which was correlated with more severe neuropsychiatric symptoms, especially affective symptoms. 19 We previously reported that argyrophilic grain disease (AGD), whose pathological features include the presence of punctate or filiform structures in the neuropil of limbic regions and the temporal lobe, may be a significant risk factor for suicide attempts in older adults with a clinical history of acute post-stroke depression 16 or incipient progressive supranuclear palsy lesions. 17 Furthermore, we recently showed that AGD may contribute to the progression of functional impairment of the limbic system, leading to psychiatric disorders and suicide attempts.…”

Tau-PET in early cortical Alzheimer brain regions in relation to mild behavioral impairment in older adults with either normal cognition or mild cognitive impairment

“…Our representation of Braak I consisted of a weighted mean of the left and right entorhinal cortices only, normalized to the inferior cerebellar grey matter consistent with other ADNI studies (Yasuno et al, 2020). Tauopathies first become apparent within the entorhinal cortex during AD pathological progression (Cho et al, 2016), advancing to the hippocampus and then other temporal lobe structures.…”

“…Post-mortem studies have determined that tau is the best predictor of global cognitive status, clinical dementia stage, functional abilities, and NPS (Malpas et al, 2020). In persons with dementia, or mixed samples including dementia, some studies have demonstrated associations between tau and NPS (Banning et al, 2020; Bloniecki et al, 2014; Koppel et al, 2013; Tommasi et al, 2021; Yasuno et al, 2020). In persons without dementia, some small to mid-size studies have found associations between tau and NPS (Ng et al, 2021).…”

Aberrant Dopamine System Function in the Ferrous Amyloid Buthionine (FAB) Rat Model of Alzheimer’s Disease

“…The neuropathology of AD is characterized by extracellular plaques which contain amyloid β (Aβ) peptide and neurofibrillary tangles with hyperphosphorylated tau. Few studies have demonstrated a relationship between AD pathology and its correlation with neuropsychiatric disorders; however, it has been suggested that AD pathologies may be associated with neuropsychiatric symptoms in the early stages of the disease [ 24 , 25 , 26 , 27 , 28 ]. Aβ is, indeed, produced in healthy brains, and is required for synaptic plasticity [ 29 ]; however, Aβ can dose-dependently affect learning and memory [ 30 ].…”