title: Association of Physical Function with Clinical and Subclinical Brain Disease: The Framingham Offspring Study.
abstract: Handgrip strength and gait speed are simple measures of physical capability and have been associated with current and future health outcomes. However, studies on their associations with brain structure and function in middle-aged adults are lacking.
  
  
  
  To assess the relationship of fast-paced walking speed and handgrip strength with risk of dementia, Alzheimer's disease (AD), and stroke, as well as the cross-sectional associations with cognitive and brain magnetic resonance imaging (MRI) measures in a middle-aged community sample.
  
  
  
  Framingham Offspring (n = 2,176; mean age 62, 54% female) had physical function, brain MRI, and cognitive evaluations between 1999 and 2005 and were followed-up for incident dementia AD and stroke until 11 years later. We related walking speed and handgrip strength to incident dementia, AD, and stroke using Cox models, and to brain and cognitive measures using multivariable linear and logistic regression. Models were adjusted for age, sex, education, and vascular risk factors.
  
  
  
  Slow walking and weak handgrip were associated with more than 2.5-fold increase in risk of AD. Weaker handgrip was associated with an increased risk of incident stroke (HR 1.74, 95% CI: 1.12-2.70/SDU, p = 0.01) in persons ≥65 years. Both measures were associated with lower total brain volume and poorer performance on tests of visual memory, language, executive function, and visuoperceptual function. Slower gait was also related to poorer verbal memory, and weaker handgrip to poorer abstraction.
  
  
  
  Tests of walking speed and handgrip strength may serve as clinical markers of brain structure and function and may improve dementia risk prediction.
authors.affiliation: Department of Neurology, School of Medicine, Boston University, Boston, Massachusetts.
authors.forename: Erica C
authors.initials: EC
authors.lastname: Camargo
authors.affiliation: Department of Neurology, School of Medicine, Boston University, Boston, Massachusetts.|School of Public Health, University of Haifa, Haifa, Israel.
authors.forename: Galit
authors.initials: G
authors.lastname: Weinstein
authors.affiliation: Department of Neurology, School of Medicine, Boston University, Boston, Massachusetts.|Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts.|Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.affiliation: Division of Geriatric Medicine in the Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Zaldy S
authors.initials: ZS
authors.lastname: Tan
authors.affiliation: Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, California, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Department of Neurology, School of Medicine, Boston University, Boston, Massachusetts.|Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Kelly-Hayes
authors.affiliation: Department of Neurology, School of Medicine, Boston University, Boston, Massachusetts.|Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Kase
authors.affiliation: Framingham Heart Study, Framingham, Massachusetts, USA.|Department of Medicine, School of Medicine, Boston University, Boston, Massachusetts, USA.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Murabito
authors.affiliation: Department of Neurology, School of Medicine, Boston University, Boston, Massachusetts.|Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications; D001927:Brain Diseases / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003704:Dementia / Q000150:complications; D005260:Female; D018737:Hand Strength / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012111:Residence Characteristics; D012307:Risk Factors; D020521:Stroke / Q000150:complications; D016138:Walking / Q000502:physiology*
keywords: Alzheimer’s disease; brain imaging; cognitive function; dementia; gait; hand strength; observational study; stroke