Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease

Objective: To determine whether brain function is altered in cognitively no rmal individuals at high risk for AD several years before the typical age a t onset for this illness. Background: Neuropathologic alterations in AD pre cede cognitive impairment by several years. It is unknown whether functiona l alterations in neural circuitry accompany these neuropathologic changes, and if so, whether they may be detectable before onset of symptoms. Methods : We used functional MRI to compare cortical activation between two groups of cognitively normal women differing only in their risk for developing AD. Visual naming and letter fluency tasks were used to activate brain areas s ubserving object and face recognition, previously described sites of hypome tabolism and neuropathologic alteration in AD. The risk groups differed in family history of AD and apolipoprotein E allele status, but were matched i n age, education, and measures of cognitive performance. Average age of the study participants was 52 years. Results: The regional patterns of brain a ctivation were similar between groups. However, the high risk group showed areas of significantly reduced activation in the mid- and posterior inferot emporal regions bilaterally during both tasks despite identical naming and letter fluency performance. Conclusions: Cognitively normal individuals at high risk for AD demonstrate decreased brain activation in key areas engage d during naming and fluency tasks. Decreased activation in the high risk gr oup may be a consequence of the presence of subclinical neuropathology in t he inferotemporal region or in the inputs to that region. If so, these find ings provide evidence of a window of opportunity for disease-modifying trea tment before the onset of symptomatic AD.