Research Spotlight: Diagnostic Accuracy of the Boston Criteria v2.0 in Memory Clinic Patients
Abstract
Background and Objectives: Cerebral amyloid angiopathy (CAA) is common in older adults and frequently contributes to cognitive impairment and dementia. Existing in vivo diagnostic criteria for CAA (Boston Criteria) were developed primarily in patients with intracerebral hemorrhage, and their performance in memory clinic populations remains uncertain. The updated Boston Criteria v2.0 incorporate nonhemorrhagic MRI markers intended to improve case detection. We evaluated the diagnostic accuracy of the Boston Criteria v1.5 and v2.0 against neuropathologically confirmed CAA in memory clinic patients.
Methods: We performed a retrospective diagnostic accuracy study of participants from the Alzheimer’s Disease Neuroimaging Initiative and National Alzheimer’s Coordinating Center, selected based on availability of required brain MRI and autopsy-based neuropathology data. Patients were classified as no, possible, or probable CAA according to the Boston Criteria v1.5 and v2.0. The primary reference standard was moderate-to-severe neuropathologic CAA; analyses using any neuropathologic CAA were secondary/exploratory. Diagnostic performance was assessed using sensitivity, specificity, predictive values, likelihood ratios, F1 scores, accuracy, and area under the (receiver-operating characteristic) curve (AUC), with formal comparisons between criteria versions.
Results: Eighty patients were included (mean age: 81 years, interquartile range 74–86 years; 36.2% female, ;80% with dementia and Alzheimer disease). Using moderate-to-severe CAA as the neuropathologic reference standard, probable CAA by Boston Criteria v1.5 had a sensitivity of 32% (95% CI 15%–50%), specificity 87% (77%–95%), and AUC 0.59 (0.49–0.69). Using the Boston Criteria v2.0, the corresponding values were 43% (25%–62%), 83% (72%–92%), and 0.63 (0.52–0.74), respectively. No overall performance measures were significantly different between the criteria versions. Secondary analyses using any neuropathologic CAA showed similar patterns.
Discussion: In memory clinic patients, both Boston Criteria versions showed only modest overall diagnostic performance against neuropathology. Compared with v1.5, Boston Criteria v2.0 showed a numerical shift toward greater sensitivity at the expense of specificity but no clear overall gain in accuracy. These findings support cautious, context-dependent interpretation of MRI-based CAA criteria in memory clinic settings and highlight the need for additional biomarkers to improve in vivo diagnosis in nonhemorrhagic populations.
Classification of Evidence: This study provides Class II evidence that, in memory clinic populations, Boston Criteria v2.0 show a trade-off between sensitivity and specificity for probable CAA diagnosis, with only modest overall diagnostic accuracy for identifying moderate-to-severe neuropathologically defined CAA.
Q&A with Author: Antreas Charidimou
What is this paper about and why are the results important?
Cerebral amyloid angiopathy, or CAA, is a common disease of the brain’s small blood vessels in older adults and frequently coexists with Alzheimer disease. We tested how well the widely used Boston Criteria can identify CAA in memory clinic patients by comparing MRI-based diagnoses with the “gold standard” of CAA found at brain autopsy. In this population, the updated Boston Criteria v2.0 identified somewhat more patients with CAA than the previous criteria, but this came at the cost of more false-positive diagnoses, and overall diagnostic accuracy remained modest.
The key message is that CAA does not look the same in every clinical setting. The Boston Criteria perform very well in patients with the more classic hemorrhagic forms of CAA, but they are less effective at detecting the often subtler, nonhemorrhagic CAA encountered in patients being evaluated for cognitive impairment. This is increasingly important as clinicians need to recognize CAA not only to understand contributors to cognitive decline but also to assess the safety of newer anti-amyloid treatments, for which underlying CAA can increase the risk of amyloid-related imaging abnormalities, or ARIA.
How do the findings relate to the brain and recovery?
CAA affects the health of the brain’s small blood vessels and can contribute to cognitive decline, brain injury, and the brain’s vulnerability to additional disease or treatment-related complications. Accurately identifying this vascular pathology is therefore an important part of understanding an individual’s overall brain health and the biological factors that may influence cognitive function and recovery.
Although this was a diagnostic rather than a rehabilitation study, its findings have important implications for brain recovery research. They show that we need better biomarkers of vascular brain health, particularly for patients who do not have the classic hemorrhagic manifestations of CAA. More accurate detection of CAA could ultimately improve patient stratification, treatment selection, assessment of treatment risk, and our ability to understand how vascular and neurodegenerative pathologies interact to influence cognitive trajectories and the brain’s capacity to maintain or recover function. The study therefore points toward a broader goal central to brain recovery research: moving beyond a single MRI finding or diagnostic label toward more precise, multimodal characterization of the brain’s underlying health.
Kropp, E., Varkanitsa, M., Stein, T. D., Turk, K., Alosco, M. L., Tripodis, Y., Romero, J. R., Kiran, S., Budson, A. E., & Charidimou, A. (2026). Diagnostic Accuracy of the Boston Criteria v2.0 in Memory Clinic Patients: An MRI-Neuropathology Validation Study. Neurology, 107(4), e218314. https://doi.org/10.1212/WNL.0000000000218314
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