Anticholinergic drugs and forebrain magnetic resonance imaging changes in cognitively normal people and those with mild cognitive impairment

Meng, Dewen; Mohammadi-Nejad, Ali-Reza; Sotiropoulos, Stamatios N.; Auer, Dorothee P.

Abstract

Background
Anticholinergic (AC) medication use is associated with cognitive decline and dementia, which may be related to an AC induced central hypocholinergic state, but the exact mechanisms remain to be understood. We aimed to further elucidate the putative link between AC drug prescription, cognition and structural and functional impairment of the forebrain cholinergic nucleus basalis of Meynert (NBM).

Methods
Cognitively normal (CN, n=344) and mild cognitively impaired (MCI, n=224) ADNI-3 participants with good quality 3T-MRI were included. Structural (regional grey matter [GM] density) and functional NBM integrity (functional connectivity [FC]) were compared between those on anticholinergic medication for over one year (AC+) and those without (AC-) in each condition. AC burden was classed as mild, moderate or severe.

Results
MCIAC+ participants (0.55±0.03) showed lower NBM-GM density compared to MCIAC- participants (0.56± 0.03, P=0.002) but there was no structural AC effect in CN. NBM-FC was lower in CNAC+ vs. CNAC- (3.6±0.5 vs. 3.9±0.6; P=0.001), and in MCIAC+ vs. MCIAC- (3.3±0.2 vs. 3.7±0.5; P<0.001) with larger effect size in MCI. NBM-FC partially mediated the association between AC medication burden and cognition.

Conclusions
Our findings provide novel support for a detrimental effect of mild AC medication on the forebrain cholinergic system characterised as functional central hypocholinergic that partially mediated AC-related cognitive impairment. Moreover, structural tissue damage suggests neurodegeneration, and larger effect sizes in MCI point to enhanced susceptibility for AC medication in those at risk of dementia.

Citation

Meng, D., Mohammadi-Nejad, A., Sotiropoulos, S. N., & Auer, D. P. (2022). Anticholinergic drugs and forebrain magnetic resonance imaging changes in cognitively normal people and those with mild cognitive impairment. European Journal of Neurology, 29(5), 1344-1353. https://doi.org/10.1111/ene.15251

• Journal Article Type: Article
• Acceptance Date: Jan 13, 2022
• Online Publication Date: Feb 7, 2022
• Publication Date: May 1, 2022
• Deposit Date: Feb 7, 2022
• Publicly Available Date: Feb 8, 2023
• Journal: European Journal of Neurology
• Print ISSN: 1351-5101
• Electronic ISSN: 1468-1331
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 5
• Pages: 1344-1353
• DOI: https://doi.org/10.1111/ene.15251
• Keywords: Anticholinergic drugs; forebrain; nucleus basalis of Meynert; grey matter density; functional connectivity; cognition 2
• Public URL: https://nottingham-repository.worktribe.com/output/7343371
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/ene.15251