Intracranial Atherosclerotic Plaques May Signify Mild Cognitive Impairment, Dementia

The association between intracranial atherosclerotic disease and dementia should be the focus of future studies.

The presence of any kind of atherosclerotic plaque or stenosis in the brain is associated with a higher risk of mild cognitive impairment (MCI) or dementia, according to results of the ARIC study (Atherosclerosis Risk in Communities) reported by Dearborn and colleagues1 in a recent issue of Neurology.

Of the 1744 patients enrolled in the population-based ARIC study from 4 US sites, 601 had MCI and 83 had dementia (weighted prevalence 22% and 3%, respectively). Women had lower rates of both MCI and dementia, although they made up 58.6% of the total cohort. Prior to enrollment in the ARIC Neurocognitive study, patients had completed 4 previous study visits with magnetic resonance imaging (MRI) and cognitive evaluations during the period from 1987 to 1999.

For the ARIC trial visit conducted between 2011 and 2013 (when the participants were all between 66 and 90 years of age), they underwent high-resolution 3-D black blood (BB) magnetic resonance imaging (MRI) of the vessel walls, a technique known to detect the thickness and burden of intracranial atherosclerotic disease (ICAD). At that time, 56% of patients with dementia had MRI-confirmed ICAD compared with 37.9% of patients with MCI and 35% of cognitively normal participants.

Specific markers by location on BBMRI correlated with different cognitive states. There were significant correlations between the prevalence of MCI with any plaque, particularly plaques involving the posterior circulation of the brain; plaques of the anterior cerebral artery (ACA); or with more than 50% stenosis. The prevalence of dementia was significantly associated with any plaque isolated to a single location other than the basilar artery, and the presence of more than 50% or 70% stenosis.

In multivariate analysis, the presence of posterior cerebral artery (PCA) plaques was strongly associated with MCI but not dementia, and the number of territories affected by plaques did not significantly influence the prevalence of MCI.

The prevalence of dementia did correlate with the presence of ACA plaques, even after controlling for vascular risk factors. The investigators also found the presence of plaques in more than 2 vascular territories or more than 50% stenosis to be strongly associated with dementia.

The ARIC study indicated that the number of plaques was a potential factor in the prevalence of dementia, supporting the results of previous autopsy studies.2-5 Nearly half (46%; n=291) of the patients with ICAD in the ARIC study were shown to have plaque in more than 1 of the 4 territories, with increased association with both MCI and dementia (mean number of plaques 1.0 and 1.7, respectively, compared with 0.9 for normal cognition).

The investigators wrote that the ARIC study “highlights that it may be important to investigate the associations with ICAD and dementia because many people have ICAD alone.” A planned follow-up of the ARIC cohort will hopefully confirm ICAD as a useful biomarker for risk of future cognitive decline.


  1. Knopman DS, Guallar E, Wasserman BA. Intracranial atherosclerosis and dementia: The Atherosclerosis Risk in Communities (ARIC) study. Neurology. 2017;88:1556-1563.
  2. Roher AE, Tyas SL, Maarouf CL, et al. Intracranial atherosclerosis as a contributing factor to Alzheimer’s disease dementia. Alzheimer’s Demen. 2011;7:436-444.
  3. Beach TG, Wilson JR, Sue LI, et al. Circle of Willis atherosclerosis: association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathol. 2007;113:13-21.
  4. KalbackW, Esh C, Castano EM, et al. Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer’s disease. Neurol Res. 2004;26:525-539.
  5. Honig LS, Kukull W, Mayeux R. Atherosclerosis and AD: analysis of data from the US national Alzheimer’s coordinating center. Neurology. 2005;64:494–500.