Association of brain amyloidosis with the incidence and frequency of neuropsychiatric symptoms in ADNI: a multisite observational cohort study

Abstract

ObjectiveTo investigate the relationship between amyloid burden and frequency of existing and incidence of new neuropsychiatric symptoms (NPS) in elderly with and without cognitive decline.Methods275 cognitively normal controls (NC), 100 subjective memory complaint (SMC), 559 mild cognitive impairment (MCI) and 143 Alzheimer’s disease dementia subjects from the Alzheimer’s Disease Neuroimaging Initiative received (18F)-florbetapir positron emission tomography (PET) scans. Yearly neuropsychiatric inventory (Neuropsychiatric Inventory (NPI)/NPI-Questionnaire) data were collected from the study partners at each visit. Mean standard uptake volume ratios (SUVR) normalised to whole cerebellum were obtained. Positive amyloid PET scan was defined as mean SUVR ≥1.17. Fisher’s exact test was used to compare frequency and incidence between amyloid positive and amyloid negative subjects. Survival analyses were used to estimate of neuropsychiatric symptoms (NPS) between amyloid positive and amyloid negative subjects. Survival analyses were used to estimate hazard ratios for developing the most common NPS by amyloid status.ResultsNo differences in NPS frequency were seen between amyloid positive and amyloid negative NC, SMC, MCI or dementia groups. MCI subjects with amyloid pathology however tended to have greater frequency x severity (FxS) of anxiety, hallucinations, delusions, apathy, disinhibition, irritability, aberrant motor behavior, and appetite, but not agitation, depression, night-time disturbances, or elation. MCI subjects with amyloid pathology were at greater risk for developing apathy, anxiety and agitation over time. Baseline presence of agitation and apathy and new onset agitation, irritability and apathy predicted faster conversion to dementia among MCI subjects.ConclusionsAmyloid pathology is associated with greater rate of development of new NPS in MCI. Anxiety and delusions are significant predictors of amyloid pathology. Agitation, irritability and apathy are significant predictors for conversion from MCI to dementia.

Plasma β-amyloid in mild behavioural impairment – neuropsychiatric symptoms on the Alzheimer’s continuum

“…39 As well, another study determined that new-onset apathy, agitation, and irritability predicted faster progression from MCI to AD. 58 A systematic review and meta-analysis determined that the most common NPS in AD is apathy (49%), followed by depression (42%) and aggression (40%). 59 Considering the high prevalence of MBI decreased motivation in dementia, it is unsurprising that the association between Aβ 42 /Aβ 40 and apathy trended towards significance in this small sample.…”

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

“…Therefore, we recruited actively depressed patients without a diagnosis of MCI or dementia. In contrast, most previous amyloid-PET studies have focused on a history of depression or depressive symptoms in healthy subjects [13][14][15] or subjects who were already diagnosed with MCI or AD at the time of scanning [67,68]. However, there is a possibility that the underlying neurobiology of a psychiatric disorder (e.g.…”

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

“…[3][4][5] Although AD is usually considered a cognitive disorder, almost all individuals diagnosed with AD develop neuropsychiatric symptoms (NPS) at some stage during the disease course, and NPS have been associated with a higher likelihood for cognitive decline. 6 A cohort study of older CN adults, those with subjective cognitive concerns, and those with mild cognitive impairment (MCI) indicated that more severe affective symptoms, including depression, irritability, agitation, disinhibition, anxiety, and apathy, were predictive of a more rapid progression of cognitive decline across all groups. 7 In a prospective cohort study estimating the risk of incident MCI in CN subjects with or without NPS at baseline, the prevalence of symptoms, including irritability, agitation, disinhibition, anxiety, and apathy, was shown to increase the risk for later MCI.…”

“…8 Furthermore, studies estimating the risk of the onset of AD in subjects with MCI showed that NPS, such as agitation, depression, and apathy, are associated with the progression from MCI to AD. 6 To date, a few groups have studied the relationship between NPS and amyloid burden, and some have suggested that NPS reflect the underlying amyloid pathology. 9,10 A high cortical amyloid burden or abnormal cerebrospinal fluid Aβ levels have been shown to be associated with apathy, anxiety, depression, and irritability.…”

“…In a prospective cohort study estimating the risk of incident MCI in CN subjects with or without NPS at baseline, the prevalence of symptoms, including irritability, agitation, disinhibition, anxiety, and apathy, was shown to increase the risk for later MCI 8 . Furthermore, studies estimating the risk of the onset of AD in subjects with MCI showed that NPS, such as agitation, depression, and apathy, are associated with the progression from MCI to AD 6 …”