Multiple microbleeds are related to cerebral network disruptions in patients with early Alzheimer's disease.
BACKGROUND
Cerebral microbleeds are a manifestation of small vessel disease and are common in patients with Alzheimer's disease (AD). However, their clinical significance in this condition is uncertain. We hypothesized that microbleeds contribute to disturbances of the cerebral network in AD and as such may affect cognition.


OBJECTIVE
The goal of this study was to examine the relationship between microbleeds and brain networks in patients with amnestic mild cognitive impairment (aMCI) or early AD.


METHODS
Sixty-seven patients (77.9 ± 7.5 years) with aMCI (n = 29) or early AD (n = 38) underwent cognitive testing and 3Tesla MRI. Microbleeds were rated visually. Diffusion tensor imaging and graph theoretical analysis were used to reconstruct brain networks and to quantify network efficiency for each patient. Network measures were compared between patients without and with ≥1 microbleeds and between patients without or with ≥3 microbleeds. In secondary analyses, cognitive functioning was compared between groups. Analyses were adjusted for age and gender, and additionally for other markers of small vessel disease and atrophy.


RESULTS
Network measures did not differ between patients with ≥1 microbleed (n = 26) and patients without microbleeds (n = 41). However, patients with ≥3 microbleeds (n = 11) showed significant white matter disruptions, longer path length, and less global efficiency than patients without microbleeds, independent of other markers of small vessel disease and atrophy. Cognitive functioning did not differ between patients without microbleeds and patients with ≥1 or ≥3 microbleeds.


CONCLUSIONS
Multiple microbleeds are related to structural network disruption in patients with early AD, but their direct impact on cognitive functioning appears to be limited.
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Sophie M
SM
Heringa
Yael D
YD
Reijmer
Alexander
A
Leemans
Huiberdina L
HL
Koek
L Jaap
LJ
Kappelle
Geert Jan
GJ
Biessels
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000473:pathology*; D016009:Chi-Square Distribution; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D056324:Diffusion Tensor Imaging; D056344:Executive Function; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008606:Mental Processes; D009415:Nerve Net / Q000473:pathology*; D009483:Neuropsychological Tests; D014706:Verbal Learning
Alzheimer's disease; cerebral amyloid angiopathy; cerebral small vessel disease; cognition; diffusion tensor imaging; magnetic resonance imaging; microbleeds; mild cognitive impairment; network