0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Association of Cerebral Microbleeds With Cognitive Decline and Dementia

Saloua Akoudad, MD, PhD1,2,3; Frank J. Wolters, MD1,3; Anand Viswanathan, MD, PhD4; Renée F. de Bruijn, MD, PhD1,3; Aad van der Lugt, MD, PhD2; Albert Hofman, MD, PhD1; Peter J. Koudstaal, MD, PhD3; M. Arfan Ikram, MD, PhD1,2,3; Meike W. Vernooij, MD, PhD1,2
[+] Author Affiliations
1Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
2Department of Radiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
3Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
4Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
JAMA Neurol. 2016;73(8):934-943. doi:10.1001/jamaneurol.2016.1017.
Text Size: A A A
Published online

Importance  Cerebral microbleeds are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. To date, whether their presence is associated with cognitive deterioration in the general population remains unclear.

Objective  To determine whether microbleeds, and more specifically microbleed count and location, are associated with an increased risk for cognitive impairment and dementia in the general population.

Design, Setting, and Participants  The Rotterdam Study, a prospective population-based study set in the general community, assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on magnetic resonance imaging studies of the brain in 4841 participants 45 years or older. Participants underwent neuropsychological testing at 2 points a mean (SD) of 5.9 (0.6) years apart and were followed up for incident dementia throughout the study period until January 1, 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed-effects modeling, and Cox proportional hazards.

Exposures  Cerebral microbleed presence, location, and number.

Main Outcomes and Measures  Cognitive decline measured by a decrease in neuropsychological test battery scores (Mini-Mental State Examination, Letter Digit Substitution Task, Word Fluency Test, Stroop test, 15-word Verbal Learning Test, and Purdue Pegboard Test) and compound scores (eg, G factor, executive function, information processing speed, memory, motor speed) and dementia.

Results  In total, 3257 participants (1758 women [54.7%]; mean [SD] age, 59.6 [7.8] years) underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3% (median [interquartile range] count, 1 [1-88]). The presence of more than 4 microbleeds was associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with a decline in executive functions (mean difference in z score, −0.31; 95% CI, −0.51 to −0.11; P = .003), information processing (mean difference in z score, −0.44; 95% CI, −0.65 to −0.22; P < .001), and memory function (mean difference in z score, −0.34; 95% CI, −0.64 to −0.03; P = .03), whereas microbleeds in other brain regions were associated with a decline in information processing and motor speed (mean difference in z score, −0.61; 95% CI, −1.05 to −0.17; P = .007). After a mean (SD) follow-up of 4.8 (1.4) years, 72 participants developed dementia, of whom 53 had Alzheimer dementia. The presence of microbleeds was associated with an increased risk for dementia after adjustment for age, sex, and educational level (hazard ratio, 2.02; 95% CI, 1.25-3.24), including Alzheimer dementia (hazard ratio, 2.10; 95% CI, 1.21-3.64).

Conclusions and Relevance  In the general population, a high microbleed count was associated with an increased risk for cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Figures

Place holder to copy figure label and caption
Figure.
Cerebral Microbleeds and Decline in Specific Cognitive Domains

Age-, sex-, educational level–, and baseline cognition-adjusted z scores are shown for decline in specific cognitive domains for categories of lobar and deep or infratentorial microbleed count compared with a reference group without cerebral microbleeds. The cognitive domains are described in the Assessment of Cognitive Functioning subsection of the Methods section. Error bars represent 95% CIs.

Graphic Jump Location

Tables

References

Correspondence

CME


You need to register in order to view this quiz.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

1,841 Views
0 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Evidence to Support the Update

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Evidence to Support the Update

brightcove.createExperiences();