title: A new visual rating scale to assess strategic white matter hyperintensities within cholinergic pathways in dementia.
abstract: OBJECTIVE
  One possible mechanism of cognitive decline in individuals with subcortical vascular disease is disruption of cholinergic fibers by ischemic lesions, such as strategically located white matter hyperintensities (WMH). The authors applied a new MRI visual rating scale to assess WMH within cholinergic pathways in patients with Alzheimer Disease (AD) and subcortical ischemic microvascular disease.
  
  
  METHODS
  Subjects included 60 AD patients with and without WMH, matched for age, as well as 15 control subjects. A visual rating scale was developed based on published immunohistochemical tracings of the cholinergic pathways in humans. On 4 selected axial images, the severity of WMH in the cholinergic pathways was rated on a 3-point scale for ten regions, identified with major anatomical landmarks. A published, consensus-derived, general WMH scale was also applied. All subjects underwent standardized neuropsychological testing.
  
  
  RESULTS
  The Cholinergic Pathways HyperIntensities Scale showed reliability and was validated with volumetry of strategic WMH. After accounting for age and education in a multiple linear regression model, The Cholinergic Pathways HyperIntensities Scale ratings were associated with impaired performance on the Mattis Dementia Rating Scale (r=0.40; P=0.02) and accounted for 12% of the variance (corrected r2). A similar model was not significant for general WMH scores.
  
  
  CONCLUSIONS
  The new MRI rating scale for WMH in cholinergic pathways is reliable and shows stronger correlations with cognitive performance than a general WMH rating scale in AD with WMH. This new rating scale provides indirect evidence that localization of WMH within neurotransmitter systems may contribute to cognitive decline.
authors.affiliation: Division of Neurology, Department of Medicine, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, QC, Canada. cbocti@gmail.com
authors.forename: Christian
authors.initials: C
authors.lastname: Bocti
authors.forename: Richard H
authors.initials: RH
authors.lastname: Swartz
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Gao
authors.forename: Demetrios J
authors.initials: DJ
authors.lastname: Sahlas
authors.forename: Pearl
authors.initials: P
authors.lastname: Behl
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D015140:Dementia, Vascular / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology; D049292:Leukoaraiosis; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008609:Mental Status Schedule; D008833:Microcirculation / Q000473:pathology; D015233:Models, Statistical; D009474:Neurons / Q000378:metabolism; D009483:Neuropsychological Tests; D018377:Neurotransmitter Agents / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012720:Severity of Illness Index; D013997:Time Factors; D014796:Visual Perception
chemical_list: D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic