title: Cardiorespiratory Fitness Attenuates the Influence of Amyloid on Cognition.
abstract: The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer's disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer's Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD.
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Schultz
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Boots
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Rodrigo P
authors.initials: RP
authors.lastname: Almeida
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Oh
authors.affiliation: 5Division of Cardiology,University of Wisconsin School of Medicine and Public Health,Madison,Wisconsin.
authors.forename: Jean
authors.initials: J
authors.lastname: Einerson
authors.affiliation: 5Division of Cardiology,University of Wisconsin School of Medicine and Public Health,Madison,Wisconsin.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Korcarz
authors.affiliation: 2Wisconsin Alzheimer's Disease Research Center,University of Wisconsin School of Medicine and Public Health,Madison,Wisconsin.
authors.forename: Dorothy F
authors.initials: DF
authors.lastname: Edwards
authors.affiliation: 3Wisconsin Alzheimer's Institute,University of Wisconsin School of Medicine and Public Health,Madison,Wisconsin.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Koscik
authors.affiliation: 7Department of Biostatistics & Medical Informatics,University of Wisconsin School of Medicine and Public Health,Madison,Wisconsin.
authors.forename: Maritza N
authors.initials: MN
authors.lastname: Dowling
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gallagher
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Bendlin
authors.affiliation: 2Wisconsin Alzheimer's Disease Research Center,University of Wisconsin School of Medicine and Public Health,Madison,Wisconsin.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
authors.affiliation: 10Clinical Neurochemistry Laboratory,Institute of Neuroscience and Physiology,The Sahlgrenska Academy at the University of Gothenburg,Mölndal,Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: 10Clinical Neurochemistry Laboratory,Institute of Neuroscience and Physiology,The Sahlgrenska Academy at the University of Gothenburg,Mölndal,Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Carlsson
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.affiliation: 2Wisconsin Alzheimer's Disease Research Center,University of Wisconsin School of Medicine and Public Health,Madison,Wisconsin.
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Hermann
authors.affiliation: 2Wisconsin Alzheimer's Disease Research Center,University of Wisconsin School of Medicine and Public Health,Madison,Wisconsin.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sager
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: 5Division of Cardiology,University of Wisconsin School of Medicine and Public Health,Madison,Wisconsin.
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.affiliation: 1Geriatric Research Education and Clinical Center,William S. Middleton Memorial Veterans Hospital,Madison,Wisconsin.
authors.forename: Ozioma C
authors.initials: OC
authors.lastname: Okonkwo
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000814:Aniline Compounds / Q000493:pharmacokinetics; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000209:etiology / Q000534:rehabilitation*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005080:Exercise Test; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010101:Oxygen Consumption; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010809:Physical Fitness / Q000502:physiology*; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D013844:Thiazoles / Q000493:pharmacokinetics; D014706:Verbal Learning
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; Amyloid; Cerebrospinal fluid; Cognition; Neuroimaging; Physical fitness