Increasing Required Neural Response to Expose Abnormal Brain Function in Mild Versus Moderate or Severe Alzheimer's Disease: PET Study Using Parametric Visual Stimulation

OBJECTIVE: The authors examined the interaction of Alzheimer's disease severity and visual stimulus complexity in relation to regional brain function. METHOD: Each subject had five positron emission tomography [¹⁵]H₂O scans while wearing goggles containing a grid of red lights embedded into each lens. Regional cerebral blood flow (CBF) was measured at 0 Hz and while lights were flashed alternately into the two eyes at 1, 4, 7, and 14 Hz. Changes in regional CBF from the 0-Hz baseline were measured at each frequency in 19 healthy subjects (mean age=65 years, SD=11), 10 patients with mild Alzheimer's disease (mean age=69, SD=5; Mini-Mental State score ≥20), and 11 patients with moderate to severe Alzheimer's disease (mean age=73, SD=12; Mini-Mental State score ≤19). RESULTS: As pattern-flash frequency increased, CBF responses in the comparison group included biphasic rising then falling in the striate cortex, linear increase in visual association areas, linear decrease in many anterior areas, and a peak at 1 Hz in V5/MT. Despite equivalent resting CBF and CBF responses to low frequencies among all groups, the groups with Alzheimer's disease had significantly smaller CBF responses than the comparison group at the frequency producing the largest response in the comparison group in many brain regions. Also, patients with moderate/severe dementia had smaller responses at frequencies producing intermediate responses in comparison subjects. CONCLUSIONS: Functional failure was demonstrated in patients with mild dementia when large neural responses were required and in patients with moderate/severe dementia when large and intermediate responses were required.