Slowing gait and risk for cognitive impairment: The hippocampus as a shared neural substrate

Neurology. 2017 Jul 25;89(4):336-342. doi: 10.1212/WNL.0000000000004153. Epub 2017 Jun 28.


Objective: To identify the shared neuroimaging signature of gait slowing and cognitive impairment.

Methods: We assessed a cohort of older adults (n = 175, mean age 73 years, 57% female, 65% white) with repeated measures of gait speed over 14 years, MRI for gray matter volume (GMV) at year 10 or 11, and adjudicated cognitive status at year 14. Gait slowing was calculated by bayesian slopes corrected for intercepts, with higher values indicating faster decline. GMV was normalized to intracranial volume, with lower values indicating greater atrophy for 10 regions of interest (hippocampus, anterior and posterior cingulate, primary and supplementary motor cortices, posterior parietal lobe, middle frontal lobe, caudate, putamen, pallidum). Nonparametric correlations adjusted for demographics, comorbidities, muscle strength, and knee pain assessed associations of time to walk with GMV. Logistic regression models calculated odds ratios (ORs) of gait slowing with dementia or mild cognitive impairment with and without adjustment for GMV.

Results: Gait slowing was associated with cognitive impairment at year 14 (OR per 0.1 s/y slowing 1.47; 95% confidence interval 1.04-2.07). The right hippocampus was the only region that was related to both gait slowing (ρ = -0.16, p = 0.03) and cognitive impairment (OR 0.17, p = 0.009). Adjustment for right hippocampal volume attenuated the association of gait slowing with cognitive impairment by 23%.

Conclusions: The association between gait slowing and cognitive impairment is supported by a shared neural substrate that includes a smaller right hippocampus. This finding underscores the value of long-term gait slowing as an early indicator of dementia risk.

MeSH terms

  • Aged
  • Apolipoproteins E / genetics
  • Arthralgia / complications
  • Atrophy
  • Cognitive Dysfunction / complications*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / physiopathology*
  • Comorbidity
  • Female
  • Follow-Up Studies
  • Functional Laterality
  • Gait Disorders, Neurologic / complications*
  • Gait Disorders, Neurologic / diagnostic imaging
  • Gait Disorders, Neurologic / genetics
  • Gait Disorders, Neurologic / physiopathology*
  • Gray Matter / diagnostic imaging
  • Gray Matter / physiopathology
  • Hippocampus / diagnostic imaging
  • Hippocampus / physiopathology*
  • Humans
  • Knee Joint
  • Magnetic Resonance Imaging
  • Male
  • Muscle Strength
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiopathology
  • Organ Size
  • Prospective Studies
  • Risk


  • Apolipoproteins E