Application of an amyloid and tau classification system in subcortical vascular cognitive impairment patients

Abstract

Objective

To apply an AT (Aβ/tau) classification system to subcortical vascular cognitive impairment (SVCI) patients following recently developed biomarker-based criteria of Alzheimer’s disease (AD), and to investigate its clinical significance.

Methods

We recruited 60 SVCI patients who underwent the neuropsychological tests, brain MRI, and 18F-florbetaben and 18F-AV1451 PET at baseline. As a control group, we further recruited 27 patients with AD cognitive impairment (ADCI; eight Aβ PET-positive AD dementia and 19 amnestic mild cognitive impairment). ADCI and SVCI patients were classified as having normal or abnormal Aβ (A−/A+) and tau (T−/T+) based on PET results. Across the three SVCI groups (A−, A+T−, and A+T+SVCI), we compared longitudinal changes in cognition, hippocampal volume (HV), and cortical thickness using linear mixed models.

Results

Among SVCI patients, 33 (55%), 20 (33.3%), and seven (11.7%) patients were A−, A+T−, and A+T+, respectively. The frequency of T+ was lower in A+SVCI (7/27, 25.9%) than in A+ADCI (14/20, 70.0%, p = 0.003) which suggested that cerebral small vessel disease affected cognitive impairments independently of A+. A+T−SVCI had steeper cognitive decline than A−SVCI. A+T+SVCI also showed steeper cognitive decline than A+T−SVCI. Also, A+T−SVCI had steeper decrease in HV than A−SVCI, while cortical thinning did not differ between the two groups. A+T+SVCI had greater global cortical thinning compared with A+T−SVCI, while declines in HV did not differ between the two groups.

Conclusion

This study showed that the AT system successfully characterized SVCI patients, suggesting that the AT system may be usefully applied in a research framework for clinically diagnosed SVCI.

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Data availability

Anonymous data are available to qualified investigators upon request to the corresponding author.

Abbreviations

Aβ:

Amyloid-β

SVCI:

Subcortical vascular cognitive impairment

HV:

Hippocampal volume

AD:

Alzheimer’s disease

NIA-AA:

National Institute on Aging and Alzheimer’s Association

PET:

Positron emission tomography

CSF:

Cerebrospinal fluid

CSVD:

Cerebral small vessel disease

MCI:

Mild cognitive impairment

ADCI:

Alzheimer’s disease–related cognitive impairment

WMH:

White matter hyperintensities

MRI:

Magnetic resonance imaging

NC:

Normal control

ADD:

Alzheimer’s disease dementia

SUVR:

Standardized uptake value ratios

ROI:

Region of interest

PVE:

Partial volume effect

FLAIR:

Fluid-attenuated inversion recovery

GRE:

Gradient echo

CMBs:

Cerebral microbleeds

BAPL:

Brain Aβ plaque load

SNSB:

Seoul Neuropsychological Screening Battery

SVLT:

Seoul Verbal Learning Test

RCFT:

Rey–Osterrieth Complex Figure Test

KBNT:

Korean version of the Boston Naming Test

MMSE:

Mini-Mental State Examination

CDR-SB:

Clinical Dementia Rating sum of boxes

ICV:

Intracranial volume

ANOVA:

Analysis of variance

ANCOVA:

Analysis of covariance

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Funding

This research was supported by funds (2018-ER6202-01) from Research of Korea Centers for Disease Control and Prevention; the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3C7A1913844); NRF grant funded by the Korea government (2017R1A2B2005081)

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Correspondence to Sang Won Seo.

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Jang, H., Kim, H.J., Park, S. et al. Application of an amyloid and tau classification system in subcortical vascular cognitive impairment patients. Eur J Nucl Med Mol Imaging 47, 292–303 (2020). https://doi.org/10.1007/s00259-019-04498-y

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Keywords

  • Amyloid-β
  • Tau
  • Classification
  • Subcortical vascular cognitive impairment
  • Longitudinal changes