Strategic subcortical hyperintensities in cholinergic pathways and executive function decline in treated Alzheimer patients.
OBJECTIVE
To investigate changes in cognition, function, and behavior after 1 year in patients with Alzheimer disease being treated with cholinesterase inhibitors, in relation to the presence or absence of subcortical hyperintensities involving the cholinergic pathways.


METHODS
One-year prospective cohort study.


METHODS
Memory Clinic, Sunnybrook Health Sciences Centre, University of Toronto. Patients Ninety patients with possible/probable Alzheimer disease who were being treated with cholinesterase inhibitors at baseline.


METHODS
Yearly standardized neuropsychological testing and brain magnetic resonance imaging (MRI). The Cholinergic Pathways Hyperintensities Scale (CHIPS) was applied to baseline MRIs to rate the severity of subcortical hyperintensities in cholinergic pathways. The consensus-derived Age-Related White Matter Changes (ARWMC) Rating Scale was used as a general measure of white matter disease burden.


METHODS
Tests of global cognition, function, and behavior and specific cognitive and functional domains.


RESULTS
Patients in the low CHIPS group were equivalent to those in the high CHIPS group with regard to baseline demographic characteristics, cognitive severity, and vascular risk factors. After covarying age and education, no differences were found after 1 year in overall cognition, function, and behavior or on memory, language, and visuospatial tasks. Patients in the high CHIPS group showed improvement on executive function and working memory tasks compared with those in the low CHIPS group. For the ARWMC scale, groups with and without white matter abnormalities were equivalent on baseline demographics and in cognitive, functional, and behavioral outcomes.


CONCLUSIONS
Cerebrovascular compromise of the cholinergic pathways may be a factor that contributes more selectively than does total white matter lesion burden to response to cholinergic therapy in Alzheimer disease, particularly on frontal/executive tasks.
Behl
Pearl
P
Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 160 Russell Jarvis Drive, Toronto, Ontario, Canada. pearl.behl@gmail.com
Bocti
Christian
C
Swartz
Richard H
RH
Gao
FuQiang
F
Sahlas
Demetrios J
DJ
Lanctot
Krista L
KL
Streiner
David L
DL
Black
Sandra E
SE
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D016009:Chi-Square Distribution; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008609:Mental Status Schedule; D015999:Multivariate Analysis; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011340:Problem Solving / Q000187:drug effects*; D011950:Receptors, Cholinergic / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic