Functional neuroanatomy of successful paired associate learning in Alzheimer's disease.
OBJECTIVE
The purpose of the study was to develop a strategy for functional imaging of neurodegenerative disorders that overcomes confounds associated with differential performance between patient and comparison groups.


METHODS
Functional magnetic resonance imaging was used to examine responses to increasing difficulty of visuospatial paired associate learning in 12 patients with mild probable Alzheimer's disease and 12 age-matched healthy comparison subjects. Performance was matched across groups by only examining successful encoding and retrieval attempts. Adjustment for task difficulty was made on an individual basis so that the patients with Alzheimer's disease and the comparison subjects performed at the same relative levels of difficulty.


RESULTS
A network of lateral and medial frontoparietal and occipital regions was engaged in all subjects during successful associative learning. As task difficulty increased, blood-oxygen-level-dependent responses increased linearly in occipitoparietal regions during encoding and retrieval. Differential activations in patients with Alzheimer's disease and comparison subjects were small and were found only when an uncorrected statistical threshold was used.


CONCLUSIONS
By controlling for confounds of varying task difficulty and subsequent performance, remarkably similar brain activations were identified during successful paired associate learning in patients with Alzheimer's disease and in healthy comparison subjects. The study methods provide a useful model for further applications of functional imaging involving cognitive activation paradigms in the study of neuropsychiatric disorders.
Gould
Rebecca L
RL
Section of Old Age Psychiatry, Box P070, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. r.gould@iop.kcl.ac.uk
Brown
Richard G
RG
Owen
Adrian M
AM
Bullmore
Edward T
ET
Williams
Steven C R
SC
Howard
Robert J
RJ
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D015577:Geriatric Assessment; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D008568:Memory / Q000502:physiology*; D009483:Neuropsychological Tests; D009778:Occipital Lobe / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010153:Paired-Associate Learning / Q000502:physiology*; D010296:Parietal Lobe / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology
D010100:Oxygen