Subregional volume reduction of the cholinergic forebrain in subjective cognitive decline (SCD).

Lukas Scheef,Alexander Koppara,Henning Boecker,Stefan Teipel,Michel J Grothe,Hans Biersack,Hans H Schild,Marcel Daamen,Frank Jessen,Michael Wagner

doi:10.1016/j.nicl.2018.101612

Abstract

Subjective cognitive decline (SCD) patients are considered as a risk population for preclinical Alzheimer's Disease (AD). Supporting this idea, previous studies in SCD populations report subtle alterations in various cognitive and neuroimaging biomarkers that are typically affected during AD progression. To extend these observations, the present study examined whether SCD patients show atrophy of cholinergic basal forebrain nuclei (chBFN), analogous with recent findings in prodromal and clinical AD patients. We assessed volume reductions of the chBFN in 24 SCD subjects compared to 49 matched controls on 3D-T1-weighted MR images based on a postmortem derived atlas. Furthermore, we assessed whether chBFN atrophy was linked with cognitive, structural and metabolic biomarker alterations we previously reported in this SCD cohort: Using correlation analyses we tested for associations between the volumes of the chBFN with the hippocampal gray matter volume, and posterior medial glucose consumption, and the trajectory of verbal memory performance. The SCD cases showed a significant total volume reduction of the chBFN, with largest effect sizes in the Ch1/2 and Ch4p subdivisions of the chBFN. The latter was associated with a reduced glucose metabolism in the precuneus for the SCD group only. These data show an early involvement of the cholinergic basal forebrain nuclei in SCD predominantly in Ch1/2 and Ch4p which supports the conceptual link between SCD and preclinical AD.

Highlights

The research focus of early disease detection in Alzheimer's disease (AD) is moving to the preclinical stage, where cognitive performance levels are still in the normal range (Sperling et al, 2014; Sperling et al, 2011)
All participants scored within 1.5 standard deviations (SD) of the mean according to age, gender, and education adjusted norms2 on all subtests of the CERAD test battery
Consistent with the idea that subjective cognitive decline (SCD) patients show a higher risk of preclinical, AD-related neuroimaging and cognitive alterations, we were able to show that the cholinergic basal forebrain volume was smaller in SCD compared to controls matched for age, gender and ApoE status, consistent with previous findings in mild cognitive impairment (MCI) and AD dementia

Summary

Introduction

The research focus of early disease detection in Alzheimer's disease (AD) is moving to the preclinical stage, where cognitive performance levels are still in the normal range (Sperling et al, 2014; Sperling et al, 2011). Identification of these cognitively normal at-risk individuals is based on biological markers, either genetic risk factors (e.g. familial predisposition, or APOE epsilon 4 carriers), or by direct measurement of amyloid depositions using cerebral spinal fluid (CSF) assays or positron emission tomography (PET). A recent study (Peter et al, 2014) observed that SCD

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