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

Maurits Johansson; Erik Stomrud; Per Mårten Johansson; Anna Svenningsson; Sebastian Palmqvist; Shorena Janelidze; Danielle van Westen; Niklas Mattsson-Carlgren; Oskar Hansson

doi:10.1016/j.biopsych.2022.01.012

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

Biol Psychiatry. 2022 Jul 1;92(1):34-43. doi: 10.1016/j.biopsych.2022.01.012. Epub 2022 Jan 31.

Authors

Maurits Johansson¹, Erik Stomrud², Per Mårten Johansson³, Anna Svenningsson², Sebastian Palmqvist², Shorena Janelidze⁴, Danielle van Westen⁵, Niklas Mattsson-Carlgren⁶, Oskar Hansson⁷

Affiliations

¹ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Division of Clinical Sciences Helsingborg, Department of Clinical Sciences Lund, Lund University, Helsingborg, Sweden; Clinical Department of Psychiatry, Helsingborg Hospital, Helsingborg, Sweden. Electronic address: maurits.johansson@med.lu.se.
² Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
³ Division of Clinical Sciences Helsingborg, Department of Clinical Sciences Lund, Lund University, Helsingborg, Sweden; Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
⁴ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
⁵ Diagnostic Radiology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Image and Function, Skåne University Hospital Lund, Lund, Sweden.
⁶ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden; Department of Neurology, Skåne University Hospital Lund, Lund, Sweden.
⁷ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden. Electronic address: oskar.hansson@med.lu.se.

PMID: 35346458
DOI: 10.1016/j.biopsych.2022.01.012

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 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.

Trial registration: ClinicalTrials.gov NCT01208675.

Keywords: Alzheimer’s disease; Amyloid; Anxiety; Apathy; Longitudinal; Neuropsychiatric symptoms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease* / complications
Alzheimer Disease* / diagnostic imaging
Amyloid beta-Peptides
Anxiety
Apathy*
Biomarkers
Cognitive Dysfunction* / etiology
Cognitive Dysfunction* / pathology
Depression
Humans
Positron-Emission Tomography
Prospective Studies
tau Proteins

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins

Associated data

ClinicalTrials.gov/NCT01208675