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Cited by 39Dementia and Cognitive Impairment ResearchParkinson's Disease Mechanisms and TreatmentsNeurological diseases and metabolism

Longitudinal atrophy in prodromal dementia with Lewy bodies points to cholinergic degeneration

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Kantarci, Kejal, Nedelska, Zuzana, Chen, Qin, Senjem, Matthew L., Schwarz, Christopher G., Gunter, Jeffrey L., Przybelski, Scott A., Lesnick, Timothy G. +16 more·2022·Brain Communications
DOI 10.1093/braincomms/fcac013PMC PMC8994111
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Abstract

Mild cognitive impairment with the core clinical features of dementia with Lewy bodies is recognized as a prodromal stage of dementia with Lewy bodies. Although grey matter atrophy has been demonstrated in prodromal dementia with Lewy bodies, longitudinal rates of atrophy during progression to probable dementia with Lewy bodies are unknown. We investigated the regional patterns of cross-sectional and longitudinal rates of grey matter atrophy in prodromal dementia with Lewy bodies, including those who progressed to probable dementia with Lewy bodies. Patients with mild cognitive impairment with at least one core clinical feature of dementia with Lewy bodies (mean age = 70.5; 95% male), who were enrolled in the Mayo Clinic Alzheimer’s Disease Research Center and followed for at least two clinical evaluations and MRI examinations, were included (n = 56). A cognitively unimpaired control group (n = 112) was matched 2:1 to the patients with mild cognitive impairment by age and sex. Patients either remained stable (n = 28) or progressed to probable dementia with Lewy bodies (n = 28) during a similar follow-up period and pathologic confirmation was available in a subset of cases (n = 18). Cross-sectional and longitudinal rates of grey matter atrophy were assessed using voxel-based and atlas-based region of interest analyses. At baseline, prodromal dementia with Lewy bodies was characterized by atrophy in the nucleus basalis of Meynert both in those who remained stable and those who progressed to probable dementia with Lewy bodies (P < 0.05 false discovery rate corrected). Increase in longitudinal grey matter atrophy rates were widespread, with greatest rates of atrophy observed in the enthorhinal and parahippocampal cortices, temporoparietal association cortices, thalamus and the basal ganglia, in mild cognitive impairment patients who progressed to probable dementia with Lewy bodies at follow-up (P < 0.05 false discovery rate corrected). Rates of inferior temporal atrophy were associated with greater rates of worsening on the clinical dementia rating–sum of boxes. Seventeen of the 18 (94%) autopsied cases had Lewy body disease. Results show that atrophy in the nucleus basalis of Meynert is a feature of prodromal dementia with Lewy bodies regardless of proximity to progression to probable dementia with Lewy bodies. Longitudinally, grey matter atrophy progresses in regions with significant cholinergic innervation, in alignment with clinical disease progression, with widespread and accelerated rates of atrophy in patients who progress to probable dementia with Lewy bodies. Given the prominent neurodegeneration in the cholinergic system, patients with prodromal dementia with Lewy bodies may be candidates for cholinesterase inhibitor treatment.

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  • Kantarci et al. showed at baseline prodromal DLB was associated with atrophy in the nucleus basalis of Meynert, measured through region of interest analysis from an in-house atlas of the substantia inominata.

    “They showed that at baseline prodromal DLB was associated with atrophy in the nucleus basalis of Meynert, measured through region of interest analysis from an in-house atlas of the substantia inominata [28].”

    From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [28]

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Authors
Kantarci, K., Nedelska, Z., Chen, Q., Senjem, M. L., Schwarz, C. G., Gunter, J. L., Przybelski, S. A., Lesnick, T. G., Kremers, W. K., Fields, J. A., Graff-Radford, J., Savica, R., Jones, D., Botha, H., Knopman, D. S., Lowe, V., Graff-Radford, N. R., Murray, M. M., Dickson, D. W., Reichard, R. R., Jack, C. R., Petersen, R. C., Ferman, T. J., & Boeve, B. F.
Affiliations
  • Mayo Clinic (US)
  • Department of Radiology, Mayo Clinic, Rochester, MN, USA
  • Department of Neurology, Mayo Clinic, Rochester, MN, USA
  • Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
  • Mayo Clinic in Florida (US)
Corresponding author
Kantarci, Kejal
ORCID
Venue
Brain Communications
Publisher
Oxford University Press (OUP)
Published
2022-02-07
Volume
4
Issue
2
Pages
fcac013-fcac013
ISSN
2632-1297 (ISSN-L)
DOI
10.1093/braincomms/fcac013
PMC
PMC8994111
OpenAlex
W4210772063
Cited by
39
References
6
Citations by year
2026: 8 · 2025: 9 · 2024: 9 · 2023: 11 · 2022: 2
FWCI
5.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (U01 NS100620, P50 AG16574, U01 AG06786, R01 AG11378)
  • Lewy Body Disease Research
  • Lewy Body Dementia Association
  • Little Family Foundation
  • Turner Family Foundation
  • Katherine B. Andersen Foundation
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
prodromal dementia with Lewy bodies, gray matter atrophy, cholinergic degeneration, nucleus basalis of Meynert, mild cognitive impairment, disease progression, entorhinal cortex, parahippocampal cortex, thalamus, basal ganglia, inferior temporal cortex, Clinical Dementia Rating, Lewy bodies, cholinergic innervation, neurodegeneration

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