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Cerebrovascular disease
Original research
Cerebellar atrophy and its implications on gait in cerebral amyloid angiopathy
  1. Mitchell J Horn1,
  2. Elif Gokcal1,
  3. Alex J Becker2,
  4. Alvin S Das1,
  5. Andrew D Warren1,
  6. Alzheimer Disease Neuroimaging Initiative,
  7. Kristin Schwab1,
  8. Joshua. N Goldstein3,
  9. Alessandro Biffi1,
  10. Jonathan Rosand1,
  11. Jonathan R Polimeni4,
  12. Anand Viswanathan1,
  13. Steven M Greenberg1,
  14. M Edip Gurol1
  1. 1 J Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
  2. 2 Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
  3. 3 Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
  4. 4 Athinoula A Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, USA
  1. Correspondence to Dr M Edip Gurol, Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA; edip{at}mail.harvard.edu

Abstract

Objective Recent data suggest that cerebral amyloid angiopathy (CAA) causes haemorrhagic lesions in cerebellar cortex as well as subcortical cerebral atrophy. However, the potential effect of CAA on cerebellar tissue loss and its clinical implications have not been investigated.

Methods Our study included 70 non-demented patients with probable CAA, 70 age-matched healthy controls (HCs) and 70 age-matched patients with Alzheimer’s disease (AD). The cerebellum was segmented into percent of cerebellar subcortical volume (pCbll-ScV) and percent of cerebellar cortical volume (pCbll-CV) represented as percent (p) of estimated total intracranial volume. We compared pCbll-ScV and pCbll-CV between patients with CAA, HCs and those with AD. Gait velocity (metres/second) was used to investigate gait function in patients with CAA.

Results Patients with CAA had significantly lower pCbll-ScV compared with both HC (1.49±0.1 vs 1.73±0.2, p<0.001) and AD (1.49±0.1 vs 1.66 ± 0.24, p<0.001) and lower pCbll-CV compared with HCs (6.03±0.5 vs 6.23±0.6, p=0.028). Diagnosis of CAA was independently associated with lower pCbll-ScV compared with HCs (p<0.001) and patients with AD (p<0.001) in separate linear regression models adjusted for age, sex and presence of hypertension. Lower pCbll-ScV was independently associated with worse gait velocity (β=0.736, 95% CI 0.28 to 1.19, p=0.002) in a stepwise linear regression analysis including pCbll-CV along with other relevant variables.

Interpretation Patients with CAA show more subcortical cerebellar atrophy than HC or patients with AD and more cortical cerebellar atrophy than HCs. Reduced pCbll-ScV correlated with lower gait velocity in regression models including other relevant variables. Overall, this study suggests that CAA causes cerebellar injury, which might contribute to gait disturbance.

  • gait
  • amyloid
  • cerebrovascular disease
  • neuroanatomy
  • cerebellar degeneration

Data availability statement

Data are available upon reasonable request. Data for this study were gathered from two sources: (1) data obtained as part of an approved study by the institutional review board of Massachusetts General Hospital; these data are not publicly available but may be available upon reasonable request; and (2) data collected from the Alzheimer’s Disease Neuroimaging Initiative and is available in their public open-access repository.

https://doi.org/10.1136/jnnp-2021-328553

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    Data availability statement

    Data are available upon reasonable request. Data for this study were gathered from two sources: (1) data obtained as part of an approved study by the institutional review board of Massachusetts General Hospital; these data are not publicly available but may be available upon reasonable request; and (2) data collected from the Alzheimer’s Disease Neuroimaging Initiative and is available in their public open-access repository.

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    Footnotes

    • Twitter @alvindasMD, @guroledip

    • Collaborators Part of the data used in preparation of this article was obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at the online supplemental file. These authors are members of the ADNI group who provided the comparator data.

    • Contributors MJH, EG, SMG and MEG contributed to the conception and design of the study; MJH, EG, AJB, ADW, ADNI, KS, JNG, AB, JR, JRP, AV, SMG and MEG contributed to the acquisition and analysis of the data; and MJH, EG, AJB, ASD, SMG and MEG contributed to drafting of the manuscript and/or figures. MEG acted as the guarantor.

    • Funding This study was supported by National Institutes of Health (NINDS R01NS114526 (MEG) and NINDS AG26484 (SMG)).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.