Neurodegeneration, Alzheimer's disease biomarkers, and longitudinal verbal learning and memory performance in late middle age

Samantha L Allison; Erin M Jonaitis; Rebecca L Koscik; Bruce P Hermann; Kimberly D Mueller; Robert P Cary; Yue Ma; Howard A Rowley; Cynthia M Carlsson; Sanjay Asthana; Henrik Zetterberg; Kaj Blennow; Barbara B Bendlin; Sterling C Johnson

doi:10.1016/j.neurobiolaging.2021.01.030

Neurodegeneration, Alzheimer's disease biomarkers, and longitudinal verbal learning and memory performance in late middle age

Neurobiol Aging. 2021 Jun:102:151-160. doi: 10.1016/j.neurobiolaging.2021.01.030. Epub 2021 Feb 4.

Authors

Affiliations

¹ Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
² Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
³ Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Communication Sciences and Disorders, University of Wisconsin, Madison, WI, USA.
⁴ Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁵ Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁶ Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Institute of Neurology, University College London, London, UK; UK Dementia Research Institute at UCL, London, UK.
⁸ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁹ Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: scj@medicine.wisc.edu.

PMID: 33765428
PMCID: PMC8286465
DOI: 10.1016/j.neurobiolaging.2021.01.030

Abstract

This study examined the effect of neurodegeneration, and its interaction with Alzheimer's disease (AD) cerebrospinal fluid biomarkers, on longitudinal verbal learning and memory performance in cognitively unimpaired (CU) late middle-aged adults. Three hundred and forty-two CU adults (cognitive baseline mean age = 58.4), with cerebrospinal fluid and structural MRI, completed 2-10 (median = 5) cognitive assessments. Learning and memory were assessed using the Rey Auditory Verbal Learning Test (RAVLT). We used sequential comparison of nested linear mixed effects models to analyze the data. Model selection preserved a significant ptau₁₈₁/Aβ₄₂ × global atrophy × age interaction; individuals with less global atrophy and lower ptau₁₈₁/Aβ₄₂ levels had less learning and delayed recall decline than individuals with more global atrophy and/or higher levels of ptau₁₈₁/Aβ₄₂. The hippocampal volume × age × ptau₁₈₁/Aβ₄₂ interaction was not significant. Findings suggest that in a sample of CU late middle-aged adults, individuals with AD biomarkers, global atrophy, or both evidence greater verbal learning and memory decline than individuals without either risk factor.

Keywords: Cerebrospinal fluid biomarkers; Global atrophy; Hippocampus; Preclinical Alzheimer's disease; Verbal learning; Verbal memory.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aging / psychology*
Alzheimer Disease / diagnosis*
Alzheimer Disease / pathology
Alzheimer Disease / psychology*
Amyloid beta-Peptides / cerebrospinal fluid
Atrophy
Biomarkers / cerebrospinal fluid
Cognition / physiology
Female
Hippocampus / pathology
Humans
Magnetic Resonance Imaging
Male
Memory / physiology*
Middle Aged
Nerve Degeneration / diagnosis*
Nerve Degeneration / psychology*
Organ Size
Peptide Fragments / cerebrospinal fluid
Verbal Learning / physiology*
tau Proteins / cerebrospinal fluid

Substances

Amyloid beta-Peptides
Biomarkers
Peptide Fragments
amyloid beta-protein (1-42)
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding