Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: Patterns of functional MRI activation

Impairment in semantic processing occurs early in Alzheimer's disease (AD) and differential impact on subtypes of semantic relations have been reporte d, yet there is little data on the neuroanatomic basis of these deficits. P atients with mild AD and healthy controls underwent 3 functional MRI audito ry stimulation tasks requiring semantic or phonological decisions (match-mi smatch) about word pairs (category-exemplar, category-function, pseudoword) . Patients showed a significant performance deficit only on the exemplar ta sk. On voxel-based fMRI activation analyses, controls showed a clear activa tion focus in the left superior temporal gyrus for the phonological task; p atients showed additional foci in the left dorsolateral prefrontal and bila teral cingulate areas. On the semantic tasks, predominant activation foci w ere seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compen satory recruitment of locally expanded foci and remote regions, for example , right frontal activation during the exemplar task. Covariance analyses in dicated that exemplar task performance was strongly related to signal incre ase in bilateral medial prefrontal cortex. The authors conclude that fMRI c an reveal similarities and differences in functional neuroanatomical proces sing of semantic and phonological information in mild AD compared to health y elderly, and can help to bridge cognitive and neural investigations of th e integrity of semantic networks in AD.