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Cerebral Microbleeds, CSF p-Tau, and Cognitive Decline: Significance of Anatomic Distribution
G C Chiang1, J C Cruz Hernandez2, K Kantarci3
1From the Department of Radiology (G.C.C.), Division of Neuroradiology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, New York gcc9004@med.cornell.edu.
Background And Purpose:
Cerebral microbleeds are associated with aging, hypertension, and Alzheimer disease. Microbleeds in a lobar distribution are believed to reflect underlying amyloid angiopathy, whereas microbleeds in the deep gray matter and infratentorial brain are commonly seen with hypertension. However, it is unknown how microbleeds in either distribution are related to Alzheimer pathogenesis. The purpose of this analysis was to test whether lobar and deep gray/infratentorial microbleeds demonstrate differential associations with CSF amyloid-β and phosphorylated tau 181 protein levels and longitudinal cognitive decline.
Materials And Methods:
A total of 626 subjects (151 cognitively normal, 389 with mild cognitive impairment, and 86 with Alzheimer disease) from the Alzheimer's Disease Neuroimaging Initiative who had undergone 3T MR imaging and lumbar puncture were included in the analysis. The number and location of microbleeds were assessed visually. Associations between lobar or deep gray/infratentorial microbleeds with CSF amyloid-β levels, abnormal CSF phosphorylated tau 181 protein levels, and longitudinal cognitive decline were assessed by using ordinary least-squares, logistic, and mixed-effects regression models while adjusting for covariates.
Results:
Having ≥3 lobar microbleeds was associated with lower levels of CSF amyloid-β (P = .001). After adjusting for CSF amyloid-β level, lobar microbleeds were independently associated with a higher likelihood of having an abnormal CSF phosphorylated tau 181 protein level (P = .004). Lobar microbleeds were associated with accelerated longitudinal cognitive decline (P = .007). Deep gray/infratentorial microbleeds revealed no significant associations.
Conclusions:
The distribution of microbleeds revealed different associations with amyloid-β and phosphorylated tau 181 protein levels and cognition. Lobar and deep gray/infratentorial microbleeds should be considered separately with regard to Alzheimer disease pathogenesis.
Insights
Lobar microbleeds, not deep ones, are linked to Alzheimer's disease markers and faster cognitive decline. This suggests distinct roles for microbleed locations in Alzheimer's pathogenesis.
Area of Science:
- Neurology
- Neuroimaging
- Biomarkers
Background:
- Cerebral microbleeds are linked to aging, hypertension, and Alzheimer's disease (AD).
- Lobar microbleeds suggest amyloid angiopathy; deep microbleeds suggest hypertension.
- The relationship between microbleed distribution and AD pathogenesis is unclear.
Purpose of the Study:
- To investigate differential associations of lobar versus deep/infratentorial microbleeds.
- To examine relationships with cerebrospinal fluid (CSF) amyloid-beta (Aβ) and phosphorylated tau 181 (p-tau181) levels.
- To assess associations with longitudinal cognitive decline in AD.
Main Methods:
- Analysis of 626 participants (cognitively normal, MCI, AD) from the Alzheimer's Disease Neuroimaging Initiative.
- 3T MR imaging and lumbar puncture were used.
- Visual assessment of microbleed number and location; regression models adjusted for covariates.
Main Results:
- ≥3 lobar microbleeds associated with lower CSF Aβ levels (P=.001).
- Lobar microbleeds independently linked to abnormal CSF p-tau181 (P=.004) and accelerated cognitive decline (P=.007).
- Deep/infratentorial microbleeds showed no significant associations.
Conclusions:
- Microbleed distribution impacts associations with AD biomarkers and cognition.
- Lobar and deep/infratentorial microbleeds have distinct roles in AD pathogenesis.
- Separate consideration of microbleed locations is crucial for understanding AD.
