Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease.
OBJECTIVE
To determine whether brain function is altered in cognitively normal individuals at high risk for AD several years before the typical age at onset for this illness.


BACKGROUND
Neuropathologic alterations in AD precede cognitive impairment by several years. It is unknown whether functional 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 subserving object and face recognition, previously described sites of hypometabolism and neuropathologic alteration in AD. The risk groups differed in family history of AD and apolipoprotein E allele status, but were matched in age, education, and measures of cognitive performance. Average age of the study participants was 52 years.


RESULTS
The regional patterns of brain activation were similar between groups. However, the high risk group showed areas of significantly reduced activation in the mid- and posterior inferotemporal 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 engaged during naming and fluency tasks. Decreased activation in the high risk group may be a consequence of the presence of subclinical neuropathology in the inferotemporal region or in the inputs to that region. If so, these findings provide evidence of a window of opportunity for disease-modifying treatment before the onset of symptomatic AD.
Smith
C D
CD
Department of Neurology, Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky College of Medicine, Lexington 40536, USA. csmith@mri.uky.edu
Andersen
A H
AH
Kryscio
R J
RJ
Schmitt
F A
FA
Kindy
M S
MS
Blonder
L X
LX
Avison
M J
MJ
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology*; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology*; D005145:Face; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010364:Pattern Recognition, Visual / Q000502:physiology; D012307:Risk Factors; D014705:Verbal Behavior / Q000502:physiology