MADRID – Even though they appear cognitively intact, carriers of the apo E4 gene show significant longitudinal decline on measures of frontally mediated cognitive skills and memory, Dr. Richard Caselli reported at the 10th International Conference for Alzheimer's Disease and Related Disorders.
“This shows that decline can occur in carriers even when it cannot be detected clinically,” said Dr. Caselli, chairman of neurology at the Mayo Clinic, Scottsdale, Ariz. “If these changes reflect early stage Alzheimer's disease, they suggest that Alzheimer's may have a preclinical phase that lasts for years and occurs even before the onset of mild cognitive impairment.”
His prospective study followed 35 apo E4 carriers and 33 noncarriers for at least 6 years, during which time all study participants received neuropsychological testing every other year. To ensure that only cognitively intact carriers were followed, Dr. Caselli excluded any patient who developed mild cognitive impairment, Alzheimer's disease, or any other form of symptomatic cognitive impairment during the study.
At baseline, the patients were a mean 56 years old, with 16 years of education; 63% were female. The testing included the revised Weschler Adult Intelligence Scale (WAIS-R) digit span, mental arithmetic, digit symbol substitution, freedom from distractibility, and controlled oral word association as measures of frontally mediated cognition.
At baseline, carriers performed slightly better than noncarriers on the auditory verbal learning test, as well as on short-term recall, long-term recall, and percent recall. However, by the end of the study period, carriers had declined significantly more than noncarriers in short-term recall as well as in mental arithmetic, digit symbol substitution, and freedom from distractibility–all frontal mediated cognitive domains.
“Aging is normally accompanied by modest declines in memory and executive skills, but in apo E4 carriers, this 'age effect' appears to be exaggerated,” Dr. Caselli said in an interview.
'Alzheimer's may have a preclinical phase that lasts for years' before onset of cognitive impairment. DR. CASELLI