Mixed handedness is associated with greater age-related decline in volumes of the hippocampus and amygdala: the PATH through life study

Handedness has been found to be associated with structural and functional cerebral differences. Left handedness and mixed handedness also appear to be associated with an elevated risk of some developmental and immunological disorders that may contribute to pathological processes developing in ageing. Inconsistent reports show that left handedness may be more prevalent in early-onset as well as late-onset Alzheimer's disease, but might also be associated with slower decline. Such inconsistencies may be due to handedness being usually modeled as a binary construct while substantial evidence suggests it to be a continuous trait. The aim of this study was to investigate the relationship between brain structures known to be implicated in pathological ageing and strength and direction of handedness. The association between handedness and hippocampal and amygdalar atrophy was investigated in 327 cognitively healthy older individuals. Handedness wasmeasured with the Edinburgh Inventory. Two measures were computed from this index, one reflecting the direction (left = 0/right = 1) and the other the degree of handedness (ranging from 0 to 1). Hippocampal and amygdalar volumes were manually traced on scans acquired 4 years apart. Regression analyses were used to assess the relationship between strength and direction of handedness and incident hippocampal and amygdalar atrophy. Analyses showed that strength but not direction of handedness was a significant predictor of hippocampal (Left: beta = 0.118, P = 0.013; Right: beta = 0.116, P = 0.010) and amygdalar (Right: beta = 0.105, P = 0.040) atrophy. The present findings suggest that mixed but not left handedness is associated with greater hippocampal and amygdalar atrophy. This effect may be due to genetic, environmental, or behavioural differences that will need further investigation in future studies.