Cholinergic Pathways Hyperintensities Scale Score Research Articles

Effects of strategic white matter hyperintensities of cholinergic pathways on basal forebrain volume in patients with amyloid-negative neurocognitive disorders

BackgroundThe cholinergic neurotransmitter system is crucial to cognitive function, with the basal forebrain (BF) being particularly susceptible to Alzheimer’s disease (AD) pathology. However, the interaction of white matter hyperintensities (WMH) in cholinergic pathways and BF atrophy without amyloid pathology remains poorly understood.MethodsWe enrolled patients who underwent neuropsychological tests, magnetic resonance imaging, and 18F-florbetaben positron emission tomography due to cognitive impairment at the teaching university hospital from 2015 to 2022. Among these, we selected patients with negative amyloid scans and additionally excluded those with Parkinson’s dementia that may be accompanied by BF atrophy. The WMH burden of cholinergic pathways was quantified by the Cholinergic Pathways Hyperintensities Scale (CHIPS) score, and categorized into tertile groups because the CHIPS score did not meet normal distribution. Segmentation of the BF on volumetric T1-weighted MRI was performed using FreeSurfer, then was normalized for total intracranial volume. Multivariable regression analysis was performed to investigate the association between BF volumes and CHIPS scores.ResultsA total of 187 patients were enrolled. The median CHIPS score was 12 [IQR 5.0; 24.0]. The BF volume of the highest CHIPS tertile group (mean ± SD, 3.51 ± 0.49, CHIPSt3) was significantly decreased than those of the lower CHIPS tertile groups (3.75 ± 0.53, CHIPSt2; 3.83 ± 0.53, CHIPSt1; P = 0.02). In the univariable regression analysis, factors showing significant associations with the BF volume were the CHIPSt3 group, age, female, education, diabetes mellitus, smoking, previous stroke history, periventricular WMH, and cerebral microbleeds. In multivariable regression analysis, the CHIPSt3 group (standardized beta [βstd] = -0.25, P = 0.01), female (βstd = 0.20, P = 0.04), and diabetes mellitus (βstd = -0.22, P < 0.01) showed a significant association with the BF volume. Sensitivity analyses showed a negative correlation between CHIPS score and normalized BF volume, regardless of WMH severity.ConclusionsWe identified a significant correlation between strategic WMH burden in the cholinergic pathway and BF atrophy independently of amyloid positivity and WMH severity. These results suggest a mechanism of cholinergic neuronal loss through the dying-back phenomenon and provide a rationale that strategic WMH assessment may help identify target groups that may benefit from acetylcholinesterase inhibitor treatment.

White matter hyperintensities in cholinergic pathways correlates of cognitive impairment in moyamoya disease.

To investigate the effect of cholinergic pathways damage caused by white matter hyperintensities (WMHs) on cognitive function in moyamoya disease (MMD). We included 62 patients with MMD from a prospectively enrolled cohort. We evaluated the burden of cholinergic pathways damage caused by WMHs using the Cholinergic Pathways Hyperintensities Scale (CHIPS). Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Cognitive impairment was determined according to the cut-off of MMSE and education. Multivariate linear and logistic regression models were used to analyze whether CHIPS was independently associated with cognition. Receiver operating characteristic curve analysis was performed to identify the ability of CHIPS in discriminating cognitive impairment and normal cognition. CHIPS was associated with both MMSE and MoCA (β = - 0.601 and β = - 0.672, both p < 0.001). After correcting age, sex, education, volumes of limbic areas, and other factors, CHIPS remained to be independently associated with both MMSE and MoCA (β = - 0.388 and β = - 0.334, both p < 0.001). In the logistic regression, only CHIPS was associated with cognitive impairment (odds ratio = 1.431, 95% confidence interval = 1.103 to 1.856, p = 0.007). The optimal cut-off of CHIPS score was 10, yielding a sensitivity of 87.5% and a specificity of 78.3% in identifying MMD patients with cognitive impairment. The damage of cholinergic pathways caused by WMHs plays an independent effect on cognition and CHIPS could be a useful method in identifying MMD patients likely to be cognitive impairment. This study shows that Cholinergic Pathways Hyperintensities Scale (CHIPS) could be a simple and reliable method in identifying cognitive impairment for patients with moyamoya disease. CHIPS could be helpful in clinical practice, such as guiding treatment decisions and predicting outcome. • Cholinergic Pathways Hyperintensities Scale was significantly associated with cognitive screening tests in patients with moyamoya disease. • Cholinergic Pathways Hyperintensities Scale plays an independent effect on cognitive impairment in patients with moyamoya disease. • Cholinergic Pathways Hyperintensities Scale shows higher accuracy than education, volumes of limbic areas, and sex in identifying cognitive impairment in moyamoya disease.

White matter hyperintensities in cholinergic pathways may predict poorer responsiveness to acetylcholinesterase inhibitor treatment for Alzheimer's disease.

Acetylcholinesterase inhibitor (AChEI) drug regimens are the mainstay treatment options for patients with Alzheimer's disease (AD). Herein, We examined the association between clinical response to AChEI and white matter hyperintensities on magnetic resonance imaging (MRI) scan at baseline. Between 2020 and 2021, we recruited 101 individuals with a clinical diagnosis of probable AD. Each participant underwent complete neuropsychological testing and 3T (Telsa) brain magnetic resonance imaging. Responsiveness to AChEI, as assessed after 12 months, was designated as less than two points of regression in Mini-Mental State Examination scores (MMSE) and stable clinical dementia rating scale. We also evaluated MRI images by examining scores on the Cholinergic Pathways Hyperintensities Scale (CHIPS), Fazekas scale, and medial temporal atrophy (MTA) scale. In our cohort, 52 patients (51.4%) were classified as responders. We observed significantly higher CHIPS scores in the nonresponder group (21.1 ± 12.9 vs. 14.9 ± 9.2, P = 0.007). Age at baseline, education level, sex, Clinical Dementia Rating sum of boxes scores, and three neuroimaging parameters were tested in regression models. Only CHIPS scores predicted clinical response to AChEI treatment. WMHs in the cholinergic pathways, not diffuse white matter lesions or hippocampal atrophy, correlated with poorer responsiveness to AChEI treatment. Therefore, further investigation into the role of the cholinergic pathway in AD is warranted.

White matter hyperintensities in cholinergic pathways are associated with dementia severity in e4 carriers but not in non-carriers.

Among individuals with Alzheimer's disease (AD), APOE e4 carriers with increased white matter hyperintensities (WMHs) may selectively be at increased risk of cognitive impairment. Given that the cholinergic system plays a crucial role in cognitive impairment, this study aimed to identify how APOE status modulates the associations between dementia severity and white matter hyperintensities in cholinergic pathways. From 2018 to 2022, we recruited participants (APOE e4 carriers, n = 49; non-carriers, n = 117) from the memory clinic of Cardinal Tien Hospital, Taipei, Taiwan. Participants underwent brain MRI, neuropsychological testing, and APOE genotyping. In this study, we applied the visual rating scale of the Cholinergic Pathways Hyperintensities Scale (CHIPS) to evaluate WMHs in cholinergic pathways compared with the Fazekas scale. Multiple regression was used to assess the influence of CHIPS score and APOE carrier status on dementia severity based on Clinical Dementia Rating-Sum of Boxes (CDR-SB). After adjusting for age, education and sex, higher CHIPS scores tended to be associated with higher CDR-SB in APOE e4 carriers but not in the non-carrier group. Carriers and non-carriers present distinct associations between dementia severity and WMHs in cholinergic pathways. In APOE e4 carriers, increased white matter in cholinergic pathways are associated with greater dementia severity. In non-carriers, WMHs exhibit less predictive roles for clinical dementia severity. WMHs on the cholinergic pathway may have a different impact on APOE e4 carriers vs. non-carriers.

Severity of Lesions Involving the Cortical Cholinergic Pathways May Be Associated With Cognitive Impairment in Subacute Ischemic Stroke.

Purpose: Impairment of cortical cholinergic pathways (CCP) is an important risk factor for chronic vascular cognitive impairment. However, this phenomenon has rarely been studied in post-stroke cognitive impairment (PSCI). We investigated the relationship between PSCI and CCP lesions assessed by structural magnetic resonance imaging (MRI).Patients and methods: We prospectively enrolled 103 patients within 7 days of ischemic stroke onset. CCP was measured by the cholinergic pathways hyperintensities scale (CHIPS), which semiquantitatively grades MR lesions strategically located on the CCP identified in human brains. We also measured other MRI parameters, including the location and volumes of acute infarcts, cerebral microbleeds, medial temporal lobe atrophy, and white matter lesions. Neuropsychological assessments were performed using the 60-min modified vascular dementia battery (VDB) at 3 months after the index stroke, and PSCI was defined according to VDB as well as ADL.Results: Of all 103 patients, 69 men (67.0%) and 34 women (33.0%) with a mean age of 57.22 ± 12.95 years, 55 patients (53.4%) were judged to have PSCI at 3 months, including 43 (41.7%) patients with PSCI-no dementia and 12 (11.7%) patients with poststroke dementia. According to the VBD assessment, the most commonly impaired cognitive domain was visuomotor speed (27.2%) followed by verbal memory (25.2%). Univariate analysis showed that patients with PSCI were older; had higher informant questionnaire on cognitive decline in the elderly (IQCODE) scores; had more frequent previous stroke history and atrial fibrillation; and had higher CHIPS scores, more severe white matter lesions, and medial temporal lobe atrophy. PSCI patients also had higher depression scores at 3 months. In the multivariate regression analysis, age, IQCODE score, CHIPS score, and Hamilton depression rating scale score were independent predictors of PSCI. Ordinal regression analysis for risk factors of poor functional outcomes revealed that IQCODE scores and cognitive function status were related to mRS score at 3 months after stroke.Conclusion: In patients with early subacute ischemic stroke, the severity of lesions involving the CCP may be associated with cognitive impairment at 3 months.Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR1800014982.

The white matter hyperintensities within the cholinergic pathways and cognitive performance in patients with Parkinson's disease after bilateral STN DBS

BackgroundWhite matter hyperintensities (WMHs) in the cholinergic pathways are associated with cognitive impairment in Parkinson's disease (PD). This study aimed to investigate the role of WMHs within the cholinergic pathways in cognitive performance following bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with PD. Methods38 patients with PD who underwent bilateral STN DBS were assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS) with magnetic resonance imaging before surgery. Their cognitive statuses were evaluated pre-surgically and 6 months, 1 year, and 2 years post operation. The correlations between the CHIPS score and cognitive performance were analyzed. The differences in cognitive performance before and after the surgery between the high-CHIPS and low-CHIPS groups were also compared. ResultsThe CHIPS score in patients with PD negatively correlated with the general cognition assessed using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) both at baseline and after DBS. No correlation was found between the CHIPS score and the change of MMSE and MoCA scores after DBS. No significant difference was observed in the change in cognitive performance after the surgery between the high and low-CHIPS groups. ConclusionThe severity of cholinergic WMHs was correlated with the cognition in patients with PD both before and after the STN DBS. However, it does not correlate with the cognitive change in patients with PD after bilateral STN-DBS.

Severe Lesions Involving Cortical Cholinergic Pathways Predict Poorer Functional Outcome in Acute Ischemic Stroke.

Background and Purpose- The aim of the study was to assess the effect of lesion severity in cortical cholinergic pathways in acute ischemic stroke patients on functional outcomes. Methods- The study sample consisted of 214 men (70.9%) and 88 women (29.1%) with acute ischemic stroke. We used the Cholinergic Pathways Hyperintensities Scale (CHIPS) to assess the severity of lesions in cortical cholinergic pathways using brain magnetic resonance imaging. The other magnetic resonance imaging parameters included infarction, white matter lesions, and medial temporal lobe atrophy. Functional outcome was assessed using the Lawton activities of daily living (ADL) scale at 3 and 6 months after the index stroke. We also assessed disability status using the modified Rankin Scale. Results- Univariate analysis showed that patients with poor functional outcomes were older, more likely to be men, had a higher National Institutes of Health Stroke Scale (NIHSS) score on admission, and had more frequent histories of previous stroke and infection complications. They also had significantly more frequent cortical infarcts, left subcortical infarcts, a larger infarct volume, more severe medial temporal lobe atrophy, and periventricular hyperintensities, and higher CHIPS scores. In the multiple regression analysis, model 1 showed that age and NIHSS score on admission were significant predictors of poor ADL at 3 months, with an R2 of 45.4% fitting the model. Age, NIHSS score on admission and stroke subtype were also significant predictors of poor ADL at 6 months, with an R2 of 37.9% fitting the model. In model 2, sex, previous stroke, NIHSS score on admission, right cortical infarcts, left subcortical infarcts and CHIPS score were significant predictors for poor ADL at 3 months, with an R2 of 53.5%. NIHSS score on admission, stroke subtype, and CHIPS score were significant predictors for poor ADL at 6 months, with an R2 of 40.2%. After adjustment for confounders, CHIPS score was also a significant predictor for poor modified Rankin Scale, both at 3 and 6 months. Even after removing patients with moderate-to-severe white matter lesions, higher CHIPS scores still correlated with poorer ADL and modified Rankin Scale both at both 3 and 6 months. Conclusions- In patients with acute ischemic stroke, cortical cholinergic pathways impairment is common, and the severity of lesions in the cortical cholinergic pathways may significantly predict a poorer functional outcome. Clinical Trial Registration- URL: http://www.chictr.org.cn/index.aspx . Unique identifier: ChiCTR1800014982.

A structural MRI study of cholinergic pathways and cognition in multiple sclerosis.

BackgroundWhite matter hyperintensities (WMH) in the cholinergic pathways are associated with cognitive performance in Alzheimer's disease. This study aimed to evaluate the relationship between the volume reduction of cholinergic pathways and cognitive function in patients with multiple sclerosis (MS).MethodsThirty-two MS patients underwent a brain MRI and cognitive measurements including the Mini-Mental State Examination (MMSE) and the Japanese version of the Montreal Cognitive Assessment (MoCA-J). The extent of WMH within the cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS). Computerized WMH volumes were also obtained. FreeSurfer was used to measure regional volumes including the cortical and subcortical volumes. The correlations among the CHIPS, the WMH volume, and the clinical data were assessed, in addition to the correlations between the cognitive scores and regional volumes measured by FreeSurfer.ResultsThe CHIPS score and the WMH volume were strongly positively correlated with each other (r = 0.87, P < 0.001). The CHIPS score had significantly negative correlations with the MMSE (r = − 0.49, P = 0.003) and the MoCA-J (r = − 0.47, P = 0.005) results. The WMH volume had significantly negative correlations with the MMSE (r = − 0.54, P = 0.001) and the MoCA-J (r = − 0.57, P < 0.001) results. In the analysis by FreeSurfer, both the MMSE and MoCA-J scores had significant positive correlations only with the volume of the corpus callosum.ConclusionsThe CHIPS score tended to be less sensitive to the WMH volume in cognitive function evaluation, although the difference did not reach the level of statistical significance. Thus the CHIPS method may not be as effective in MS patients.

Association between the extent of white matter damage and early cognitive impairment following acute ischemic stroke.

White matter (WM) injury following acute ischemic stroke (AIS) is associated with cognitive decline. Establishing relationships between the specific cognitive tests used to assess post-AIS cognition and various clinical indices of WM injury severity and distribution may aid in prognosis and early treatment decisions. We enrolled 62 patients with AIS to Weifang People's Hospital between September 2014 and August 2015. WM lesion severity and distribution were examined by computed tomography (CT) and magnetic resonance imaging (MRI). The Blennow scale was used for scoring the distribution and degree of WM lesions (WMLs) on CT images, the Fazekas scale for scoring periventricular and deep WMLs on MRI, and the Cholinergic Pathways Hyperintensities Scale (CHIPS) for scoring MRI manifestation of cholinergic fiber damage. The 8-domain Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function. Mean ± standard deviation scores on the Blennow scale was 1.6±0.5; Fazekas scale, 3.4±0.8; and CHIPS, 65.7±12.5. The proportion of patients with a MoCA score <26 (indicating cognitive dysfunction) was significantly higher in subgroups with Blennow scale score >2, Fazekas scale score >4, and CHIPS score >51 (all P<0.001). The MoCA score was negatively correlated with Blennow scale score (r=−0.326, P=0.002), Fazekas scale score (r=−0.404, P=0.031), and CHIPS score (r=−0.234, P=0.042). Thus, the degree and distribution of whole-brain, deep, and cholinergic WMLs were associated with cognitive impairment. The Blennow scale, Fazekas scale, and CHIPS all provide good predictive efficacy of post-AIS cognitive dysfunction.

Subcortical whiter matter hyperintensities within the cholinergic pathways of patients with dementia and parkinsonism

Background and purposeWhite matter hyperintensities (WMHs) in the cholinergic pathways are associated with cognitive performance in Alzheimer's disease (AD) and Parkinson disease dementia (PDD). This study aimed to evaluate the relationship between loss of white matter cholinergic pathways and cognitive function in patients with AD, diffuse Lewy body disease (DLB), and PDD. MethodsThe subjects included 20 patients with AD, 17 with DLB, 21 with PDD, and 20 healthy controls. The extent of WMHs within cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS) and was compared among the different diseases. ResultsThe mean CHIPS scores were similar among the three dementia groups (AD vs. DLB vs. PDD=34.6±17.9 vs. 32.4±14.1 vs. 31.8±14.5, p=0.781 by ANCOVA) and higher than those of controls (11.5±7.6, p=0.001 by ANCOVA). ConclusionsLosses of cholinergic pathways were similar among AD, DLB, and PDD groups, and more severe cognitive dysfunction was associated with elevated WMHs. These findings suggest that interruption of acetylcholine pathways may be related to cognitive dysfunction in these three diseases, even though they have different pathological mechanisms.

Cortical Hubs and Subcortical Cholinergic Pathways as Neural Substrates of Poststroke Dementia

A role of neural networks in the development of poststroke dementia has not been clearly established. We hypothesized that stroke-mediated disruption of subcortical cholinergic pathway or large-scale neural networks contributes to poststroke dementia. A matched case-control study was conducted in a predetermined cohort with acute ischemic stroke. Cases were defined as newly developed dementia diagnosed >3 months after stroke using the Korean Vascular Cognitive Impairment Harmonization Standards. Each case was matched to 2 controls for age, education, and initial stroke severity. The Cholinergic Pathways HyperIntensities Scale was applied with some modifications to characterize disruption of cholinergic pathways by acute stroke lesions. Involvement of major cortical hub locations of the default mode network, central executive network, and salience network was also investigated. After matching, 38 cases and 66 matched controls were included. Cholinergic Pathways HyperIntensities Scale scores were significantly higher in cases than in controls (2.2±2.9 versus 0.9±1.4). Acute ischemic lesions affecting the default mode and central executive networks were more frequently observed in cases compared with controls (36.8% versus 7.6% and 26.3% versus 6.1%, respectively). These findings remained significant in the multiple logistic regression models adjusted for various sets of potential confounders. Lesion location analysis revealed that cases were more likely to have acute lesions in the left corona radiata, hippocampal formation, and posterior parietal cortex. Disruption of cholinergic pathways and major hubs of large-scale neural networks might contribute to newly developed dementia after acute ischemic stroke.

Subcortical white matter hyperintensities within the cholinergic pathways of Parkinson's disease patients according to cognitive status

BackgroundWhite matter hyperintensities (WMH) in the cholinergic pathways show a stronger correlation with cognitive performance than general WMH in Alzheimer's disease. However, the role of WMH within the cholinergic pathways...

Silent Infarction or White Matter Hyperintensity and Impaired Attention Task Scores in a Nondemented Population: The Osaki-Tajiri Project

Whether silent infarction can be completely asymptomatic remains unclear. Although the central cholinergic system affects cognition, little attention has been given to infarction. We hypothesized that specific damage to the cholinergic pathways due to infarction or white matter hyperintensity (WMH) would deteriorate cognition, especially attention. A total of 502 representative elderly participants enrolled in the Osaki-Tajiri Project in 1998 were studied. Participants with focal neurologic signs or previous history of stroke or transient ischemic attack were excluded from the analysis. MRIs were available for all participants, and the Cholinergic Pathways Hyperintensities scale (CHIPS) was used to assess vascular damage in the cholinergic pathways. The Mini-Mental State Examination (MMSE), word fluency test, Digit Symbol test, and digit span test were used to assess global cognitive function and several aspects of attention. Participants were divided into 3 groups according to the comorbidity of cerebrovascular disease (CVD) and cholinergic involvement: non-CVD, CVD with cholinergic involvement [CVD-Ch(+)], and CVD without cholinergic involvement [CVD-Ch(-)]. Cognitive scores were compared among the 3 groups. In the non-CVD group, the correlations between cognitive function and the CHIPS score were examined. The CVD-Ch(+) group exhibited significantly lower scores for the Digit Symbol test compared with the other two groups, regardless of the MMSE score. In the non-CVD group, the CHIPS score of white matter changes was irreversibly correlated (ie, biologically meaningful) with the Digit Symbol score in participants age >80 years. Our findings suggest that silent infarction or WMH may deteriorate attention regardless of global cognitive function by interrupting the central cholinergic pathway.

The role of cholinergic pathway lesions in vascular cognitive impairment

Objective To investigate the relationship between white matter lesions (WML) within the cholinergic pathway and vascular cognitive impairment.Method Middle-aged and elderly stroke patients underwent brain MRI examination and Montreal Cognitive Assessment (MoCA).Cholinergic Pathways Hyperintensities Scale (CHIPS) scores and the overall WML burden by Schelten on fluidattenuated inversion recovery MRI images were determined and compared with MoCA scores.Spearman partial rank correlation coefficients and standardized regression coefficients were calculated.Results Thirty four patients were included ( mean age ( 62.2 ± 8.8 ) years, 45-82 years).MoCA scores negatively correlated with WML burdens by Schelten scores ( β = - 0.357, P = 0.042) and CHIPS scores ( β =-0.382,P=0.026).CHIPS scores were negatively associated with visuospatial and executive function (r = - 0.290, P = 0.048 ), naming function ( r = - 0.486, P = 0.002 ), attention ( r = - 0.311, P =0.037) and abstraction ( r = - 0.344, P = 0.023).Schelten scores were negatively associated with naming function (r = - 0.492, P = 0.002), attention ( r = - 0.364, P = 0.017) and abstraction ( r = - 0.390,P=0.011).Conclusion WML lesions within the cholinergic pathyway play a possible role in vascular cognitive impairment especially in visuospatial and executive function. Key words: Cholinergic fibers; Neurol pathways; Brain ischemia; Stroke; Congnitive disorders; Severity of illness index

A New Visual Scale to Assess White Matter Hyperintensities Within Cholinergic Pathways

Neural networks of the human cerebral cortex responsible for attention, memory, and emotions are modulated by cholinergic input from the 4 overlapping Ch1–Ch4 cell groups of the basal forebrain.1,2 Cholinergic neurons of the medial septal nucleus (Ch1 cell group) and the vertical limb nucleus of the diagonal band (Ch2) provide the major cholinergic input to the hippocampus. Cholinergic neurons of the horizontal limb nucleus of the diagonal band (Ch3) provide the major cholinergic input of the olfactory bulb, and cholinergic neurons of the nucleus basalis of Meynert (nbM-Ch4) provide the principal cholinergic input of the remaining cerebral cortex and amygdala. Trajectories of these cholinergic fibers in white matter have been described recently in humans.2 Cholinergic system damage leads to cognitive decline,3 thus, it is expected that the magnitude and extent of the damage will correlate with the degree of decline. White matter hyperintensities (WMHs) are encountered frequently on magnetic resonance (MR) scans of normal elderly people as well as in patients with various types of dementia. These hyperintensities are presumably related to small infarcts and lacunes caused by cerebrovascular …

Detecting Cognitive Dysfunction in Multiple Sclerosis with a Magnetic Resonance Imaging Rating Scale: A Pilot Study

In multiple sclerosis (MS), magnetic resonance imaging (MRI) predictors of cognitive impairment are based on sophisticated computer-generated analyses that are difficult to apply in clinical settings. This study investigated the clinical usefulness of a new visual rating scale, the Cholinergic Pathways Hyperintensities Scale (CHIPS), in detecting cognitive dysfunction. Forty clinically definite MS patients underwent a brain MRI. Based on the CHIPS, cholinergic pathway hyperintensities were rated in 10 regions on four axial slices. Computerized hyperintense lesion volumes were also obtained. For cognitive testing, The Neuropsychological Screening Battery for Multiple Sclerosis was used. "Low" and "High" lesion score groups were computed based on the mean of the total CHIPS score. Optimal sensitivity and specificity of the total CHIPS score in detecting cognitive impairment were determined using a receiver operator characteristic curve. Despite a similar demographic profile, subjects with a "High" lesion score performed significantly worse than the "Low" lesion score group on verbal (P = .007) and visuospatial (P = .02) memory, and on a global index of cognitive functioning (P = .001). Optimal sensitivity (82%) and specificity (83%) were reached with a threshold total CHIPS score of 18 points. Total CHIPS score and total hyperintense lesion load were correlated (sigma = 0.82, P < .0001). CHIPS is helpful in clinically predicting cognitive impairment in MS.