Cortical hypometabolism in Parkinson's disease is linked to cholinergic basal forebrain atrophy

Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson's disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cog...

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Veröffentlicht in:Molecular psychiatry 2024-12
Hauptverfasser: Labrador-Espinosa, Miguel A, Silva-Rodriguez, Jesús, Okkels, Niels, Muñoz-Delgado, Laura, Horsager, Jacob, Castro-Labrador, Sandra, Franco-Rosado, Pablo, Castellano-Guerrero, Ana María, Iglesias-Camacho, Elena, San-Eufrasio, Manuela, Macías-García, Daniel, Jesús, Silvia, Adarmes-Gómez, Astrid, Ojeda-Lepe, Elena, Carrillo, Fátima, Martín-Rodríguez, Juan Francisco, Roldan Lora, Florinda, García-Solís, David, Borghammer, Per, Mir, Pablo, Grothe, Michel J
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Sprache:eng
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Zusammenfassung:Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson's disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cognitive impairment and may contribute to cortical hypometabolism through cholinergic denervation of cortical projection areas. Here, we investigated in-vivo associations between subregional cBF volumes on 3T-MRI, cortical hypometabolism on [ F]FDG-PET, and cognitive deficits in a cohort of 95 PD participants with varying degrees of cognitive impairment. We further assessed the spatial correspondence of the cortical pattern of cBF-associated hypometabolism with the pattern of cholinergic denervation in PD as assessed by [ F]FEOBV-PET imaging of presynaptic cholinergic terminal density in a second cohort. Lower volume of the cortically-projecting posterior cBF, but not of the anterior cBF, was significantly associated with extensive neocortical hypometabolism [p(FDR) 
ISSN:1359-4184
1476-5578
1476-5578
DOI:10.1038/s41380-024-02842-9