Are Linear Measurements of the Nucleus Basalis of Meynert Suitable as a Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer Disease?

K.D Jethwa,D Meng,P Dhillon,D.P Auer

doi:10.3174/ajnr.a6313

Abstract

Cell loss within the nucleus basalis of Meynert is an early event in Alzheimer disease. The thickness of the nucleus basalis of Meynert (NBM) can be measured on structural MR imaging. We investigated NBM thickness in relation to cognitive state and biochemical markers. Mean bilateral nucleus basalis of Meynert thickness was measured on coronal T1-weighted MR imaging scans from the Alzheimer's Disease Neuroimaging Initiative dataset. Three hundred and fifteen scans (80 controls, 79 cases of early mild cognitive impairment, 77 cases of late mild cognitive impairment and 79 cases of Alzheimer disease) were assessed. Alzheimer's Disease Assessment Scale-Cognitive scores, CSF tau, and amyloid quantification were extracted. Group differences in NBM thickness, their correlates and measurement reliability were assessed. Mean NBM thickness ± SD progressively declined from 2.9 ± 0.3, 2.5 ± 0.3, and 2.3 ± 0.3 to 1.8 ± 0.4 mm in healthy controls, patients with early mild cognitive impairment, late mild cognitive impairment and Alzheimer disease respectively (P < .001). NBM thickness was negatively correlated with Alzheimer's Disease Assessment Scale-Cognitive scores (r = -0.53, P < .001) and weakly positively correlated with CSF amyloid (r = 0.250, P < .001) respectively. No association with CSF tau was found. NBM thickness showed excellent diagnostic accuracy to differentiate Alzheimer disease (area under the curve, 0.986) and late mild cognitive impairment from controls (area under the curve, 0.936) with excellent sensitivity, but lower specificity 66.7%. Intra- and interrater reliability for measurements was 0.66 and 0.47 (P < .001). There is progressive NBM thinning across the aging-dementia spectrum, which correlates with cognitive decline and CSF markers of amyloid-β pathology. We show high diagnostic accuracy but limited reliability, representing an area for future improvement. NBM thickness is a promising, readily available MR imaging biomarker of Alzheimer disease warranting diagnostic-accuracy testing in clinical practice.

Highlights

BACKGROUND AND PURPOSECell loss within the nucleus basalis of Meynert is an early event in Alzheimer disease
There is progressive nucleus basalis of Meynert (NBM) thinning across the aging-dementia spectrum, which correlates with cognitive decline and CSF markers of amyloid-b pathology
NBM thickness is a promising, readily available MR imaging biomarker of Alzheimer disease warranting diagnostic-accuracy testing in clinical practice

Summary

Methods

Mean bilateral nucleus basalis of Meynert thickness was measured on coronal T1-weighted MR imaging scans from the Alzheimer’s Disease Neuroimaging Initiative dataset. Three hundred and fifteen scans (80 controls, 79 cases of early mild cognitive impairment, 77 cases of late mild cognitive impairment and 79 cases of Alzheimer disease) were assessed. Alzheimer’s Disease Assessment Scale-Cognitive scores, CSF tau, and amyloid quantification were extracted. The primary goal of ADNI is to test whether serial MR imaging, PET, other biologic markers, and clinical and neuropsychological assessments can be combined to measure the progression of MCI and early AD. The sample included 80 healthy controls, 79 individuals with early MCI, 77 with late MCI, and 79 with AD Clinical cognitive assessments included the Mini-Mental State Examination and Alzheimer Disease Assessment Scale-Cognitive subscale (ADASCog). Stable dose cholinesterase inhibitors were permitted for patients with MCI and AD (ie, no dose change during the preceding 12 weeks)

Results

Discussion

Conclusion