Alterations in working memory as a function of leukoaraiosis in dementia.

Dementia research suggests executive dysfunction is best understood within the context of disease-specific neuropathology. Leukoaraiosis (LA) results in executive dysfunction yet little is known about its impact on specific aspects of working memory (WM). This study aimed to investigate the relationship between MRI LA severity and WM in dementia. A visual rating scale was used to assign patients with dementia into groups with minimal-mild LA (Low LA; n=34) and moderate-severe LA (High LA; n=32). A modified Digit Span Backward Task consisting of 3-, 4-, and 5-span trials measured specific components of WM. Short-term storage and rehearsal in WM were assessed by the total number of digits reported regardless of recall order (ANY-ORDER; e.g., 47981 recalled '18943', score=4). Mental manipulation in the form of disengagement and temporal re-ordering was assessed by the total number of digits recalled in correct position (SERIAL-ORDER; e.g., 47981 recalled '18943', score=3). There was no difference between LA groups on ANY-ORDER comparisons. The High LA group obtained lower SERIAL-ORDER scores than the Low LA group. Stepwise regression analyses were conducted that first entered MMSE scores then composite z-scores reflecting executive functioning, language and memory. ANY-ORDER performance variance was explained solely by dementia severity. SERIAL-ORDER performance variance was further explained by executive dysfunction. Results suggest that high degrees of LA do not interfere with immediate (digit) recall but do interfere with disengagement and temporal re-ordering. LA may disconnect the frontal lobes from subcortical and cortical structures that form the neuronal networks critical for these WM functions.