Aβ42/Aβ40 and Aβ42/Aβ38 Ratios Are Associated with Measures of Gait Variability and Activities of Daily Living in Mild Alzheimer's Disease: A Pilot Study

Gait disturbances are some of the earliest changes in dementia and their monitoring presents an opportunity for early diagnosis. The exact relationship between gait and well-established biomarkers of Alzheimer's disease (AD) remains to be clarified. In this study we compared gait-related measures with cerebrospinal fluid (CSF) markers of AD pathology. We recruited seventeen participants with mild AD in a multi-site study and performed gait assessment as well as lumbar punctures to obtain CSF. CSF A beta(42)/A beta(40) and( )A beta(42)/A beta(38 )correlated positively with measures of variability (step time and step length) in the clinic-based assessments. This was driven by a negative relationship between gait variability and A beta(40) and A beta(3)(8) but not A beta(42).The amyloid ratios and gait variability measures were also associated with more severe functional impairment. We interpret these data as an indication that increasing amyloid production (i.e., increasing A beta(40) and A beta(38)) is associated with diminishing cognitive-motor control of gait. These preliminary results suggest that the two amyloid ratios may be a marker of the earliest disturbances in the interplay between cognitive and motor control which characterize dementia.