White Matter Hyperintensities Of The Cholinergic Pathways And The Cognitive Function

Background：The cholinergic system is the primary neurotransmitter systemresponsible for cognitive symptoms in dementia and possibly normal aging. Thedysfunction of cholinergic system has been one of the pathological changes of AD(Alzheimer’s disease). The basal forebrain cholinergic pathways from the Mynertnucleus to the cerebral cortex and amygdala is considered to be the importantpathways for cognition, and also vulnerable to the small vessel disease.The cholinergic pathways hyperintensities scale (CHIPS) is a semiquantitativeimaging method established on the cholinergic pathways anatomy, and evaluate themagnetic resonance imaging (MRI) T2white matter hyperintensities (WMH) severityof the cholinergic pathways on axial imaging.Objectives：To evaluate the impact of WMH of cholinergic pathways oncognitive function and cognitive impairment in normal elderly, and patients with mildcognitive impairment (MCI) and AD. We investigate the prevalence and the riskfactors of the WMH of the cholinergic pathways, and its relationship with thecognitive function.Materials and methods:216subjects were involved, and divided into threegroups according to the cognition,182normal controls,23MCI individuals,11ADpatients. They were divided into three groups:<70,70and80, and>80years old. TheCHIPS, Fazekas, and ARWMC scales were selected to evaluate the WMH. The totalCHIPS score is divided into three classes according to WMH burden, the normal (0)、minimal（1-7）and severe (≥8) abnormality. MoCA was selected to be the majorcognitive assessing tool to evaluate the cognition. Clinical material and medicinehistory were collected in detail.Results：1. The prevalence of WMH of cholinergic pathways reflected by CHIPSis78.7%, minimal impairment is31.9%, and severe impairment is46.8%. In the <70 years old,70-80years old,>80years old group, CHIPS total score are5.14±6.68、11.79±12.63、13.61±10.21. The prevalence of abnormality of CHIPS was64.2%、80.3%、96.6%respectively, and the difference is significant (p=0.000).2. The prevalence of cognitive impairment (MCI+AD) in CHIPS normal,minimal and severe groups is2.2%、8.7%、26.7%respectively, and the difference issignificant (X~2=24.319, p=0.000). Logistic analysis showd that CHIPS severity had asignificant influence on the cognitive impairment (combined MCI and AD)(OR=2.858,95%CI=1.277-6.397), and increased the MCI risk significantly(OR=6.112,95%CI=1.803-20.718).Univariate analysis showed that only the language item of MoCA had significantdifference among CHIPS normal, minimal and severe groups (p=0.003). Multivariateanalysis, adjusted by age and education, showed that MoCA total score, as well aseach item, had no relationship with the CHIPS scores (p>0.05).3. CHIPS and the periventricular white matter (ρs=0.544,p=0.000) and the deepwhite matter(ρs=0.729,p=0.000) of the Fazekas have significant correlation. CHIPSand ARWMC has statistically significant correlation (r=0.819, p=0.000).4. The prevalance of hypertension in CHIPS severe group was74.3%(p<0.05).When combined normal, MCI and AD groups, multivariate analysis shows that age(p=0.002), cognitive impairment (MCI+AD)(p=0.027) and hypertension (p=0.025)are the independent risk factors for CHIPS. When the MCI and AD patients wereremoved, age still significant (p=0.001), but the hypertension just showed a nearlysignificance (p=0.068).Conclusions：1. The WMH of cholinergic pathways reflected by CHIPS iscommon in elderly, and the severity increased with age.2. The WMH of cholinergicpathways increase the risk of MCI and AD.3. Risk factors of the WMH ofcholinergic pathways include age and hypertension, and that CHIPS is correlated withFazekas and ARWMC, imply that WMH of cholinergic pathways may shair the samepathophysiological mechanism with other WML pattern.