P3-151: White matter hyperintensities within cholinergic pathways in Alzheimer's disease affecting the clock drawing test performance

Abstract

Cerebral white matter hyperintensities (WMH) are common findings on MRI in elderly people. Two possible mechanisms have been suggested: 1) by disruption of corticocortical association fibers or fronto-subcortical neuronal networks; 2) interference with cholinergic projecting pathway. The purpose of this study is to evaluate how WMH can affect on the Clock Drawing Test in Alzheimer disease (AD). One hundred twenty seven patients with AD were enrolled for this study. Subjects met the National Institute of Neurological Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) research criteria for possible or probable AD. All subjects were taken MRI to measure the severity of WMH based on visual inspection of T2-weighted and proton-density MRI. Subjects underwent standardized neuropsychological testing, including Korean versions of the Mini-Mental State Exam (MMSE) and the modified MMSE (3MS) to assess cognitive domains of interest (attention, memory, executive function) as well as general level of cognition. Clock Drawing Test (CDT) was given to all patients to analyze the level of performance and error-types. Manos scoring protocol was adopted for the evaluation of CDT results. Cognitive measures and the CDT were assessed independently by a neuropsychologist and a neurologist who were not aware of clinical information. The Age-Related White Matter Changes (ARWMC) rating scale of the European Task Force was used as a general measure of WMH severity. WMH involved in cholinergic pathways were measured by the Cholinergic Pathways Hyperintensities Scale (CHIPS). Performance of the CDT as well as overall level of cognition showed significant relation with the WMC severity. Temporal WMH in ARWMC had stronger relationship with the CDT performance than other areas. WMH of the posterior corona radiata in CHIPS showed significant correlation with the CDT performance. Interference in the cholinergic projecting pathway as well as disruption of cortico-subcortical neural networks by WMH may contribute to the impaired CDT performance in AD.