Journal Article

FZJ-2022-01186

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Age and Anterior Basal Forebrain Volume Predict the Cholinergic Deficit in Patients with Mild Cognitive Impairment due to Alzheimer’s Disease

Richter, N. (Corresponding author)FZJ* ; David, L.-S. ; Grothe, M. J. ; Teipel, S. ; Dietlein, M. ; Tittgemeyer, M. ; Neumaier, B.FZJ* ; Fink, G. R.FZJ* ; Onur, O. A. ; Kukolja, J.

2022
IOS Press Amsterdam

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Please use a persistent id in citations: http://hdl.handle.net/2128/33066  doi:10.3233/JAD-210261

Abstract: Abstract.Background: Early and severe neuronal loss in the cholinergic basal forebrain is observed in Alzheimer’s disease (AD). Todate, cholinomimetics play a central role in the symptomatic treatment of AD dementia. Although basic research indicatesthat a cholinergic deficit is present in AD before dementia, the efficacy of cholinomimetics in mild cognitive impairment(MCI) remains controversial. Predictors of cholinergic impairment could guide individualized therapy.Objective: To investigate if the extent of the cholinergic deficit, measured using positron emission tomography (PET) and thetracer 11C-N-methyl-4-piperidyl acetate (MP4A), could be predicted from the volume of cholinergic basal forebrain nucleiin non-demented AD patients.Methods: Seventeen patients with a high likelihood of MCI due to AD and 18 age-matched cognitively healthy adultsunderwent MRI-scanning. Basal forebrain volume was assessed using voxel-based morphometry and a cytoarchitectonicatlas of cholinergic nuclei. Cortical acetylcholinesterase (AChE) activity was measured using MP4A-PET.Results: Cortical AChE activity and nucleus basalis of Meynert (Ch4 area) volume were significantly decreased in MCI.The extent of the cholinergic deficit varied considerably across patients. Greater volumes of anterior basal forebrain nuclei(Ch1/2 area) and younger age (Spearman’s rho(17) = –0.596, 95%-CI [–0.905, –0.119] and 0.593, 95%-CI [0.092, 0.863]))were associated with a greater cholinergic deficit.Conclusion: Data suggest that less atrophy of the Ch1/2 area and younger age are associated with a more significant cholinergicdeficit in MCI due to AD. Further investigations are warranted to determine if the individual response to cholinomimeticscan be inferred from these measures.Keywords: Acetylcholinesterase, aging, MP4A, nucleus basalis of Meynert, positron emission tomography

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Contributing Institute(s):

1. Kognitive Neurowissenschaften (INM-3)

Research Program(s):

1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)

Appears in the scientific report 2022

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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