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Original Contribution
February 2007

Strategic Subcortical Hyperintensities in Cholinergic Pathways and Executive Function Decline in Treated Alzheimer Patients

Author Affiliations

Author Affiliations: Division of Neurology, Department of Medicine (Drs Swartz, Gao, Sahlas, and Black) and Department of Psychiatry (Drs Lanctot and Streiner), Sunnybrook Health Sciences Centre, and Institute of Medical Science, University of Toronto (Drs Behl, Swartz, Sahlas, Lanctot, Streiner, and Black), Toronto, Ontario; Division of Neurology, Department of Medicine, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec (Dr Bocti); and Kunin-Lunenfeld Applied Research Unit, Baycrest, Toronto (Dr Streiner).

Arch Neurol. 2007;64(2):266-272. doi:10.1001/archneur.64.2.266

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.

Design  One-year prospective cohort study.

Setting  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.

Interventions  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.

Main Outcome Measures  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.

Conclusion  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.