P1-269: Maternal history of Alzheimer's disease predisposes to progressive brain hypometabolism on FDG-PET

Having a parent affected with late-onset Alzheimer's disease (AD) is a risk factor for developing AD among cognitively normal (NL) subjects. We examined the association between a parental family history of AD and cerebral metabolic rates of glucose (CMRglc) on FDG-PET in NL subjects. The FDG-PET scans of 121 20–92 year-old NL, including 67 subjects with a negative family history of AD (FH–), 18 with paternal (FHp) and 36 with maternal AD (FHm), were examined to test for CMRglc differences across FH groups, and to estimate the age of onset of hypometabolism over the adult life-span. Sixty-one subjects (35 FH-, 8 FHp, and 18 FHm) with 2-year follow-up FDG-PET were examined for longitudinal CMRglc declines. As compared to FH- and FHp, FHm subjects showed CMRglc reductions in the same regions as clinical AD patients, i.e. posterior cingulate cortex/precuneus (PCC), parieto-temporal, frontal and medial temporal cortices (P's<0.05, corrected for multiple comparisons). These effects remained significant after accounting for age, gender, education, and ApoE genotype. No CMRglc differences were found between FHp and FH–. CMRglc reductions in FHm as compared to FH- and FHp reached statistical significance at age 55 years. CMRglc declined at greater rates in FHm as compared to FH- and FHp, and was further reduced by 13–23% in those FHm with the mother and maternal grandmother affected with AD (n=6) (P's<0.05). NL individuals with a maternal history of AD show hypometabolism in AD-vulnerable brain regions. The CMRglc reductions occur at middle age, are progressive, and are more severe in those with a maternal history of AD spanning two generations. FDG-PET measures may help to identify NL individuals at risk for future AD years in advance of clinical symptoms, and to direct investigation of potential susceptibility genes for AD.