Cholinergic neuromodulation in the aging brain – Implications for neuropsychiatric diseases: Commentary on “neuromodulatory systems in aging and disease” special issue

Marina Leiman, Mareike Ludwig, Friedrich Krohn, Dorothea Hämmerer, Yeo-Jin Yi

1. Introduction

The cholinergic system plays a pivotal role in both cognitive functions and affective processes. However, its significance in age-related neuropsychiatric diseases is frequently overshadowed by a predominant focus on higher-order symptoms associated with cortical pathology. Neuropsychiatric disorders encompass a wide range of symptoms affecting mood, behavior, and cognition, often without clear neurodegeneration. Neurodegenerative diseases, on the other hand, are characterized by progressive structural decline in the brain, leading to cognitive and functional decline.

Alzheimer’s Disease (AD), for instance, is typically accompanied by a significant degeneration of cholinergic neurons, particularly in the basal forebrain, contributing to cognitive decline and memory impairment, specifically. Cholinergic neurodegeneration is also linked to cognitive decline in Lewy Body Dementia and is accompanied by hallucinations and other behavioral symptoms. In Parkinson’s Disease Dementia, cognitive symptoms are similarly tied to cholinergic dysregulation, resulting in memory impairment and executive dysfunction.

Hence, the cholinergic system appears as a viable target for therapeutic interventions addressing not only cognitive but also neuropsychiatric symptoms. Understanding how the cholinergic system influences neuropsychiatric conditions can offer valuable insights and lead to potential avenues for novel treatments.

Neurosci Biobehav Rev. 161:105654 (2024)


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