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. 2020 Jun:139:104831.
doi: 10.1016/j.nbd.2020.104831. Epub 2020 Mar 5.

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

Joana B Pereira  1 , Sara Hall  2 , Mattis Jalakas  3 , Michel J Grothe  4 , Olof Strandberg  3 , Erik Stomrud  3 , Eric Westman  5 , Danielle van Westen  2 , Oskar Hansson  6
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Free article

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

Joana B Pereira et al. Neurobiol Dis. 2020 Jun.
Free article

Abstract

Objectives: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Basal forebrain; Cognitive decline; Dementia; Longitudinal MRI; Parkinson's disease.

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Conflict of interest statement

Declaration of Competing Interest OH has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Biogen and Roche. The rest of authors have no conflicts of interest.

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