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

Pereira, Joana B. LU ; Hall, Sara LU ; Jalakas, Mattis LU ; Grothe, Michel J. ; Strandberg, Olof LU ; Stomrud, Erik LU orcid ; Westman, Eric ; van Westen, Danielle LU orcid and Hansson, Oskar LU orcid (2020) In Neurobiology of Disease 139.
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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Basal forebrain, Cognitive decline, Dementia, Longitudinal MRI, Parkinson's disease
in
Neurobiology of Disease
volume
139
article number
104831
publisher
Elsevier
external identifiers
  • scopus:85081702032
  • pmid:32145376
ISSN
0969-9961
DOI
10.1016/j.nbd.2020.104831
language
English
LU publication?
yes
id
35a3deb0-ee96-4cc2-b517-8091720baee1
date added to LUP
2020-03-29 17:49:22
date last changed
2024-06-26 12:33:41
@article{35a3deb0-ee96-4cc2-b517-8091720baee1,
  abstract     = {{<p>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 &lt;.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 &lt;.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.</p>}},
  author       = {{Pereira, Joana B. and Hall, Sara and Jalakas, Mattis and Grothe, Michel J. and Strandberg, Olof and Stomrud, Erik and Westman, Eric and van Westen, Danielle and Hansson, Oskar}},
  issn         = {{0969-9961}},
  keywords     = {{Basal forebrain; Cognitive decline; Dementia; Longitudinal MRI; Parkinson's disease}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Neurobiology of Disease}},
  title        = {{Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson's disease}},
  url          = {{http://dx.doi.org/10.1016/j.nbd.2020.104831}},
  doi          = {{10.1016/j.nbd.2020.104831}},
  volume       = {{139}},
  year         = {{2020}},
}