This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective Cholinergic degeneration and β-amyloid contribute to brain atrophy and cognitive dysfunction in Alzheimer disease (AD) and Lewy body disease (LBD), but their relationship has not been comparatively evaluated.
Methods In this cross-sectional study, we recruited 28 normal controls (NC), 55 patients with AD mild cognitive impairment (MCI), 34 patients with AD dementia, 28 patients with LBD MCI, and 51 patients with LBD dementia. Participants underwent cognitive evaluation, brain MRI to measure the basal forebrain (BF) volume and global cortical thickness (CTh), and 18F-florbetaben (FBB) PET to measure the standardized uptake value ratio (SUVR). Using general linear models and path analyses, we evaluated the association of FBB-SUVR and BF volume with CTh or cognitive dysfunction in the AD spectrum (AD and NC) and LBD spectrum (LBD and NC), respectively. Covariates included age, sex, education, deep and periventricular white matter hyperintensities, intracranial volume, hypertension, diabetes, and hyperlipidemia.
Results BF volume mediated the association between FBB-SUVR and CTh in both the AD and LBD spectra, while FBB-SUVR was associated with CTh independently of BF volume only in the LBD spectrum. Significant correlation between voxel-wise FBB-SUVR and CTh was observed only in the LBD group. FBB-SUVR was independently associated with widespread cognitive dysfunction in both the AD and LBD spectra, especially in the memory domain (standardized beta [B] for AD spectrum = −0.60, B for LBD spectrum = −0.33). In the AD spectrum, BF volume was associated with memory dysfunction (B = 0.18), and CTh was associated with language (B = 0.21) and executive (B = 0.23) dysfunction. In the LBD spectrum, however, BF volume and CTh were independently associated with widespread cognitive dysfunction.
Conclusions There is a common β-amyloid–related degenerative mechanism with or without the mediation of BF in the AD and LBD spectra, while the association of BF atrophy with cognitive dysfunction is more profound and there is localized β-amyloid–cortical atrophy interaction in the LBD spectrum.
Glossary
- AD=
- Alzheimer disease;
- BF=
- basal forebrain;
- CTh=
- cortical thickness;
- DLB=
- dementia with Lewy bodies;
- 18F-FP-CIT=
- N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)nortropane;
- FBB=
- 18F-florbetaben;
- FDR=
- false discovery rate;
- FWHM=
- full width half-maximum;
- GLM=
- general linear model;
- LBD=
- Lewy body disease;
- MCI=
- mild cognitive impairment;
- NC=
- normal controls;
- PD=
- Parkinson disease;
- PDD=
- PD with dementia;
- SUVR=
- standardized uptake value ratio;
- WMH=
- white matter hyperintensities
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
- Received June 17, 2021.
- Accepted in final form December 21, 2021.
- © 2021 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
