Abstract
BackgroundThe impact of Alzheimer’s disease (AD) pathology and cognitive deficits on longitudinal neuropsychiatric symptoms is unclear, especially in early disease stages. MethodsCognitively unimpaired older adults (N = 356) enrolled in the prospective Swedish BioFINDER study were examined. Neuropsychiatric assessments encompassed the Apathy Evaluation Scale and the Hospital Anxiety and Depression Scale, performed biennially (together with tests of global cognition) for up to 8 years. Biomarkers were measured in cerebrospinal fluid or plasma at baseline. Magnetic resonance imaging quantified white matter lesions. We used linear mixed-effect models to test associations between baseline AD biomarkers (for amyloid-β [Aβ], tau, and neurodegeneration) and white matter lesions with longitudinal neuropsychiatric symptoms (apathy, anxiety, and depressive symptoms). We also tested associations between changes in cognition and changes in neuropsychiatric symptoms. Finally, we tested if change in cognition mediated the effects of different brain pathologies on neuropsychiatric symptoms. ResultsAβ pathology at baseline was associated with increasing levels of apathy (β = −0.284, p = .005) and anxiety (β = −0.060, p = .011) longitudinally. More rapid decline of cognition over time was related to increasing levels of apathy. The effects of baseline Aβ pathology on longitudinal apathy were partly mediated by changes in cognitive performance (proportion mediated 23%). ConclusionsAβ pathology may drive the development of both apathy and anxiety in very early stages of AD, largely independent of cognitive change. The effect of Aβ on apathy is only partially conveyed by worse cognition. Together, these findings highlight certain neuropsychiatric symptoms as early manifestations of AD.
Highlights
Key hallmarks of Alzheimer’s disease (AD) include cerebral amyloid-β (A ) plaques, neurofibrillary tangles of hyperphosphorylated tau, and neurodegeneration, as well as clinical manifestations including both cognitive deficits and neuropsychiatric symptoms (NPS, e.g., apathy, depression, and anxiety
We investigate how biomarkers of AD pathology, white matter lesions (WML), and cognitive deficits potentially drive the development of apathy, anxiety, and depressive symptoms in cognitively unimpaired (CU) older adults
The effect of Cerebrospinal fluid (CSF) A 42/40 over time on AES-I and Hospital Anxiety and Depression Scale (HADS)-A remained significant after correction for multiple comparisons
Summary
Key hallmarks of Alzheimer’s disease (AD) include cerebral amyloid-β (A ) plaques, neurofibrillary tangles of hyperphosphorylated tau, and neurodegeneration, as well as clinical manifestations including both cognitive deficits and neuropsychiatric symptoms (NPS, e.g., apathy, depression, and anxiety) . AD pathologies, where its clinical progression is staged according to the level of cognitive deterioration. AD pathologies, where its clinical progression is staged according to the level of cognitive deterioration2 This view is supported by a robust relationship between AD pathology and future cognitive decline. The criteria do not highlight NPS, it is known that the frequency and severity of NPS increase with worsening cognition3, 4 This suggests that NPS and cognitive deficits can develop in parallel and that NPS may constitute early manifestations of AD5. The impact of Alzheimer’s disease (AD) pathology and cognitive deficits on longitudinal neuropsychiatric symptoms is unclear, especially in early disease stages
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