ArticleBrain : a journal of neurology2024
Basal forebrain integrity, cholinergic innervation and cognition in idiopathic Parkinson's disease.
Article in Brain : a journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Feasibility, safety and efficacy of multi-dose vagus nerve stimulation in Parkinson's disease: a double-blind, randomised sham-controlled proof-of-concept study.Journal of neurology · 2025Trial
- Article
- White matter lesions disrupt cholinergic pathways important for cognition in Parkinson's disease.Brain : a journal of neurology · 2026Article
- Associations between REM sleep EEG slowing and brain cholinergic denervation in aging and Mild Cognitive Impairment.Molecular psychiatry · 2026Article
- Dopaminergic- and Cholinergic-Related Structural MRI Patterns Across Cognitive Subtypes of Parkinson's Disease With Mild Cognitive Impairment.European journal of neurology · 2026Article
- Data-driven trajectories of atrophy explain clinical heterogeneity across Lewy body diseases.medRxiv : the preprint server for health sciences · 2026Article
- Cholinergic Basal Forebrain Atrophy Accelerates Cognitive Decline via Cortical Thinning: The Moderating Role of Amyloid-β Pathology in Preclinical Alzheimer's Disease.Research square · 2026Article
- Basal Forebrain Volume and Concurrent Hallucinations and Mild Cognitive Impairment in Parkinson's Disease.Movement disorders clinical practice · 2026Article
- Whole-brain efferent projections of glutamatergic neurons in the cingulate cortex of mice.Molecular brain · 2026Article
- Wakefulness regulation of memory encoding and retrieval: structure and activity.National science review · 2026Review
- Association of dopamine depletion and cholinergic basal forebrain atrophy with brain metabolism and cognition in Parkinson's disease.Journal of Parkinson's disease · 2026Article
- Characteristics and mechanisms of cognitive impairment in Parkinson disease.Nature reviews. Neurology · 2026Review
- When Alzheimer's pathology meets cardiometabolic risk: intrinsic subcortical-cortical connectivity signatures of retroactive interference in aging.Alzheimer's research & therapy · 2026Article
- Peripheral inflammation mediates cognitive deficits in drug-naive schizophrenia through hippocampal-thalamo-visual circuitry dysfunction.Schizophrenia (Heidelberg, Germany) · 2026Article
- Potential for distinguishing the parkinsonian subtype of multiple system atrophy from Parkinson's disease: a three-dimensional gait analysis study.Frontiers in aging neuroscience · 2026Article
- Basal Forebrain Volume Predicts Disease Conversion in Prodromal Synucleinopathy.Movement disorders clinical practice · 2026Article
- JAK4D, a first-in-class thyrotropin-releasing hormone analogue, reverses scopolamine-induced memory deficits.Brain communications · 2026Article
- Cholinergic basal forebrain atrophy accelerates cognitive decline via cortical thinning: The moderating role of amyloid-β pathology in preclinical Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- Cholinergic network disruptions on cognitive function across the spectrum of cognitive impairment in Parkinson's disease.Journal of neurology · 2025Article
- Peri- and Postnatal High Fat Feeding Have Differential Effects on Executive Function and Associated Neurobiology in Aged Male and Female Mice.Aging cell · 2025Article
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5 authors.
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Abstract
Most individuals with Parkinson's disease experience cognitive decline. Mounting evidence suggests this is partially caused by cholinergic denervation due to α-synuclein pathology in the cholinergic basal forebrain. Alpha-synuclein deposition causes inflammation, which can be measured with free water fraction, a diffusion MRI-derived metric of extracellular water. Prior studies have shown an association between basal forebrain integrity and cognition, cholinergic levels and cognition, and basal forebrain volume and acetylcholine, but no study has directly investigated whether basal forebrain physiology mediates the relationship between acetylcholine and cognition in Parkinson's disease. We investigated the relationship between these variables in a cross-sectional analysis of 101 individuals with Parkinson's disease. Cholinergic levels were measured using fluorine-18 fluoroethoxybenzovesamicol (18F-FEOBV) PET imaging. Cholinergic innervation regions of interest included the medial, lateral capsular and lateral perisylvian regions and the hippocampus. Brain volume and free water fraction were quantified using T1 and diffusion MRI, respectively. Cognitive measures included composites of attention/working memory, executive function, immediate memory and delayed memory. Data were entered into parallel mediation analyses with the cholinergic projection areas as predictors, cholinergic basal forebrain volume and free water fraction as mediators and each cognitive domain as outcomes. All mediation analyses controlled for age, years of education, levodopa equivalency dose and systolic blood pressure. The basal forebrain integrity metrics fully mediated the relationship between lateral capsular and lateral perisylvian acetylcholine and attention/working memory, and partially mediated the relationship between medial acetylcholine and attention/working memory. Basal forebrain integrity metrics fully mediated the relationship between medial, lateral capsular and lateral perisylvian acetylcholine and free water fraction. For all mediations in attention/working memory and executive function, the free water mediation was significant, while the volume mediation was not. The basal forebrain integrity metrics fully mediated the relationship between hippocampal acetylcholine and delayed memory and partially mediated the relationship between lateral capsular and lateral perisylvian acetylcholine and delayed memory. The volume mediation was significant for the hippocampal and lateral perisylvian models, while free water fraction was not. Free water fraction in the cholinergic basal forebrain mediated the relationship between acetylcholine and attention/working memory and executive function, while cholinergic basal forebrain volume mediated the relationship between acetylcholine in temporal regions in memory. These findings suggest that these two metrics reflect different stages of neurodegenerative processes and add additional evidence for a relationship between pathology in the basal forebrain, acetylcholine denervation and cognitive decline in Parkinson's disease.
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