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Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults : Effects of Alzheimer's Disease Pathology and Cognitive Decline

Johansson, Maurits LU ; Stomrud, Erik LU orcid ; Johansson, Per Mårten LU ; Svenningsson, Anna L LU orcid ; Palmqvist, Sebastian LU orcid ; Janelidze, Shorena LU ; van Westen, Danielle LU orcid ; Mattsson-Carlgren, Niklas LU orcid and Hansson, Oskar LU orcid (2022) In Biological Psychiatry 92(1). p.34-43
Abstract

Background: The impact of Alzheimer's disease (AD) pathology and cognitive deficits on longitudinal neuropsychiatric symptoms is unclear, especially in early disease stages. Methods: Cognitively 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... (More)

Background: The impact of Alzheimer's disease (AD) pathology and cognitive deficits on longitudinal neuropsychiatric symptoms is unclear, especially in early disease stages. Methods: Cognitively 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. Results: Aβ 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%). Conclusions: Aβ 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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Amyloid, Anxiety, Apathy, Longitudinal, Neuropsychiatric symptoms
in
Biological Psychiatry
volume
92
issue
1
pages
34 - 43
publisher
Elsevier
external identifiers
  • scopus:85127874517
  • pmid:35346458
  • scopus:85127874517
ISSN
0006-3223
DOI
10.1016/j.biopsych.2022.01.012
language
English
LU publication?
yes
id
1644f7a6-3756-4c12-93dc-bbf3537b41f8
date added to LUP
2022-04-13 11:13:38
date last changed
2024-06-13 17:10:26
@article{1644f7a6-3756-4c12-93dc-bbf3537b41f8,
  abstract     = {{<p>Background: The impact of Alzheimer's disease (AD) pathology and cognitive deficits on longitudinal neuropsychiatric symptoms is unclear, especially in early disease stages. Methods: Cognitively 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. Results: Aβ 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%). Conclusions: Aβ 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.</p>}},
  author       = {{Johansson, Maurits and Stomrud, Erik and Johansson, Per Mårten and Svenningsson, Anna L and Palmqvist, Sebastian and Janelidze, Shorena and van Westen, Danielle and Mattsson-Carlgren, Niklas and Hansson, Oskar}},
  issn         = {{0006-3223}},
  keywords     = {{Alzheimer's disease; Amyloid; Anxiety; Apathy; Longitudinal; Neuropsychiatric symptoms}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{34--43}},
  publisher    = {{Elsevier}},
  series       = {{Biological Psychiatry}},
  title        = {{Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults : Effects of Alzheimer's Disease Pathology and Cognitive Decline}},
  url          = {{http://dx.doi.org/10.1016/j.biopsych.2022.01.012}},
  doi          = {{10.1016/j.biopsych.2022.01.012}},
  volume       = {{92}},
  year         = {{2022}},
}