Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson's disease

• Published in: Neurobiology of disease Vol. 139; p. 104831
• Main Authors: Pereira, Joana B., Hall, Sara, Jalakas, Mattis, Grothe, Michel J., Strandberg, Olof, Stomrud, Erik, Westman, Eric, van Westen, Danielle, Hansson, Oskar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2020; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Atrophy; Basal forebrain; Basal Forebrain - pathology; Case-Control Studies; Clinical Medicine; Cognition; Cognitive decline; Cognitive Dysfunction - pathology; Dementia; Dementia - pathology; Disease Progression; Female; Humans; Klinisk medicin; Longitudinal MRI; Longitudinal Studies; Magnetic Resonance Imaging; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Neurologi; Neurology; Neuropsychological Tests; Parkinson Disease - pathology; Parkinson's disease; Prospective Studies; Sweden; Young Adult; Sweden; Cognitive decline; Basal forebrain; Parkinson's disease; Longitudinal MRI; Dementia
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2020.104831

Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD. We included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PD patients were diagnosed with dementia (PD-dementia converters), whereas the rest of PD patients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline. Compared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p = .003) and those who already had PDD (p < .001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p = .004). Baseline and longitudinal Ch4 volumes were associated with cognition (p < .002) and longitudinal Ch4 atrophy predicted future dementia (p = .009). Atrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia. •Ch4 atrophy precedes and predicts future dementia in PD.•These changes are followed by Ch1/Ch2 longitudinal atrophy.•The basal forebrain shows an anterior-posterior pattern of atrophy over time in PD.