New research shows that a gene which is the major genetic risk factor for Alzheimer's disease (AD) may also influence the actual expression of the disease and account for some of the variations in the types of cognitive problems seen in patients with AD.

"This work provides proof of concept that genetics may not only impact the risk for dementia but also the nature of a dementia syndrome," said author David A. Wolk, MD, the author of a paper published online May 17 in an early edition of the Proceedings of the National Academy of Sciences United States of America.

Drs. Wolk and Bradford C. Dickerson, MD, investigated cognitive and neuroanatomical phenotypic variability in gene carriers and noncarriers with mild AD. Only patients proven to have AD on the basis of a cerebrospinal fluid molecular profile were studied. They found that APOE ε4 allele carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers displayed greater impairment on tests of working memory, executive control, and word retrieval. In addition, carriers exhibited greater medial temporal lobe atrophy, whereas noncarriers had greater frontoparietal atrophy.

"What was particularly remarkable about this study was the high correspondence between the differential effect of APOE status on cognitive symptoms and on evidence of brain atrophy," Dr. Wolk said.