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Cerebral Microbleeds in Different Brain Regions and Their Associations With the Digital Clock-Drawing Test: Secondary
Samia C Akhter-Khan1,2, Qiushan Tao2,3, Ting Fang Alvin Ang2,4,5,6
1Department of Global Health & Social Medicine, King's College London, London, United Kingdom.
Background:
Cerebral microbleeds (CMB) increase the risk for Alzheimer disease. Current neuroimaging methods that are used to detect CMB are costly and not always accessible.
Objective:
This study aimed to explore whether the digital clock-drawing test (DCT) may provide a behavioral indicator of CMB.
Methods:
In this study, we analyzed data from participants in the Framingham Heart Study offspring cohort who underwent both brain magnetic resonance imaging scans (Siemens 1.5T, Siemens Healthcare Private Limited; T2*-GRE weighted sequences) for CMB diagnosis and the DCT as a predictor. Additionally, paper-based clock-drawing tests were also collected during the DCT. Individuals with a history of dementia or stroke were excluded. Robust multivariable linear regression models were used to examine the association between DCT facet scores with CMB prevalence, adjusting for relevant covariates. Receiver operating characteristic (ROC) curve analyses were used to evaluate DCT facet scores as predictors of CMB prevalence. Sensitivity analyses were conducted by further including participants with stroke and dementia.
Results:
The study sample consisted of 1020 (n=585, 57.35% female) individuals aged 45 years and older (mean 72, SD 7.9 years). Among them, 64 (6.27%) participants exhibited CMB, comprising 46 with lobar-only, 11 with deep-only, and 7 with mixed (lobar+deep) CMB. Individuals with CMB tended to be older and had a higher prevalence of mild cognitive impairment and higher white matter hyperintensities compared to those without CMB (P<.05). While CMB were not associated with the paper-based clock-drawing test, participants with CMB had a lower overall DCT score (CMB: mean 68, SD 23 vs non-CMB: mean 76, SD 20; P=.009) in the univariate comparison. In the robust multiple regression model adjusted for covariates, deep CMB were significantly associated with lower scores on the drawing efficiency (β=-0.65, 95% CI -1.15 to -0.15; P=.01) and simple motor (β=-0.86, 95% CI -1.43 to -0.30; P=.003) domains of the command DCT. In the ROC curve analysis, DCT facets discriminated between no CMB and the CMB subtypes. The area under the ROC curve was 0.76 (95% CI 0.69-0.83) for lobar CMB, 0.88 (95% CI 0.78-0.98) for deep CMB, and 0.98 (95% CI 0.96-1.00) for mixed CMB, where the area under the ROC curve value nearing 1 indicated an accurate model.
Conclusions:
The study indicates a significant association between CMB, especially deep and mixed types, and reduced performance in drawing efficiency and motor skills as assessed by the DCT. This highlights the potential of the DCT for early detection of CMB and their subtypes, providing a reliable alternative for cognitive assessment and making it a valuable tool for primary care screening before neuroimaging referral.
Insights
The digital clock-drawing test (DCT) can identify cerebral microbleeds (CMB), a risk factor for Alzheimer disease. This accessible cognitive assessment shows promise for early CMB detection, especially deep and mixed types, aiding primary care screening.
Area of Science:
- Neurology
- Neuroimaging
- Cognitive Science
Background:
- Cerebral microbleeds (CMB) are linked to increased Alzheimer disease risk.
- Current neuroimaging methods for CMB detection are expensive and not widely accessible.
Purpose of the Study:
- To investigate the digital clock-drawing test (DCT) as a potential behavioral indicator for cerebral microbleeds (CMB).
Main Methods:
- Analysis of Framingham Heart Study offspring cohort data, including brain MRI for CMB and DCT.
- Exclusion of individuals with dementia or stroke history.
- Application of multivariable linear regression and ROC curve analyses to assess the association between DCT scores and CMB prevalence.
Main Results:
- 6.27% of 1020 participants had CMB; they were older and had higher rates of mild cognitive impairment.
- CMB presence was associated with lower overall DCT scores (P=.009).
- Deep CMB correlated with lower drawing efficiency (P=.01) and simple motor scores (P=.003) on the DCT. ROC analysis showed high accuracy for subtype discrimination (AUC up to 0.98).
Conclusions:
- The DCT demonstrates significant associations with CMB, particularly deep and mixed types.
- Reduced performance in drawing efficiency and motor skills on the DCT may indicate CMB.
- The DCT offers a promising, accessible tool for early CMB detection and cognitive screening in primary care settings.
