Volumetric MRI and cognitive measures in Alzheimer disease : comparison of markers of progression.
BACKGROUND
Both cognitive tests and MRI-based measures have been suggested as outcomes in trials assessing disease-modifying therapies in Alzheimer's disease (AD).


OBJECTIVE
To compare changes in longitudinal MRI measures with changes in performance on cognitive tests routinely used in AD clinical trials.


METHODS
Fifty-two subjects from the placebo-arm of a clinical trial in mild-to-moderate AD had volumetric T(1)-weighted scans and cognitive tests including the Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale, Disability Assessment for Dementia, AD Cooperative Study-Clinical Global Impression of Change and Clinical Dementia Rating at baseline and one-year later. Rates of brain atrophy and ventricular enlargement were measured using the boundary shift integral. Hippocampal (Hc) atrophy was calculated from manual volume measurements. The relationships between MRI and cognitive measures were investigated.


RESULTS
Rates of brain atrophy and/or ventricular enlargement were correlated with declining performance on cognitive scales. The strongest association was between brain atrophy rate and MMSE decline (r = 0.59, p < 0.0001). Hc atrophy rate was not significantly correlated with any of the cognitive scales.


CONCLUSIONS
The lack of correlation between Hc atrophy and cognitive scales may reflect a combination of: the extensive functional damage to the Hc by the time AD is clinically established, the greater influence of ongoing cortical degeneration, and errors in Hc outlining. The strong correlations between brain atrophy and ventricular enlargement, and cognitive scales probably reflect the correspondence between these measures of overall cerebral loss and global cognitive measures in the moderate stages of AD.
Ridha
Basil H
BH
Dementia Research Centre, Institute of Neurology, University College London, 8-11 Queen Square, London, WC1N 3BG, UK. bridha@dementia.ion.ucl.ac.uk
Anderson
Valerie M
VM
Barnes
Josephine
J
Boyes
Richard G
RG
Price
Shona L
SL
Rossor
Martin N
MN
Whitwell
Jennifer L
JL
Jenkins
Lisa
L
Black
Ronald S
RS
Grundman
Micheal
M
Fox
Nick C
NC
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology*; D001284:Atrophy / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010919:Placebos; D011237:Predictive Value of Tests; D011379:Prognosis
D015415:Biomarkers; D010919:Placebos