Risk Factors for Dementia Vary After Intracerebral Hemorrhage

Risk factors differ for early vs late-onset dementia after ICH.

Location and volume of intracerebral hemorrhage (ICH) have been identified as risk factors for dementia within 6 months of the event. Notably, delayed dementia after ICH had distinctly different risk factors.

Nearly half of all stroke-related disability and mortality is attributed to ICH, despite ICH accounting for only 15% of strokes. ICH and the associated morbidity is thought to be tied to underlying cerebral small-vessel disease. Further, it is thought that patients who develop ICH are at higher risk for progressive cognitive decline. However, there is limited data to explain this association.

To understand the early and long-term risk for dementia after ICH, Alessandro Biffi, MD, of the Center for Human and Genetic Research at Massachusetts General Hospital in Boston, and colleagues conducted a longitudinal study of patients with ICH. The study included 738 patients (mean age 74.3 years) with a diagnosis of ICH and no evidence of dementia. Cognitive performance was assessed by the Telephone Interview for Cognitive Status test. Outcomes were analyzed  6 months post-ICH and then every 6 months thereafter. The location of ICH and severity of white matter disease was obtained from the indexed CT scan.  Patients were tested for APOE genotype and a subset of patients underwent MRI within 90 days of ICH.

The telephone assessment was found to have a specificity of 94% and sensitivity of 90% when compared to ICD-9 codes of the attending neurologist (n=522 patients). Overall, 37.8% (n=279) of the study participants developed dementia.

The investigators identified 140 participants (19%) with incident dementia within 6 months of the ICH event. Of the 435 participants who were followed for a mean of 47.4 months, the estimated yearly incidence of dementia was approximately 5.8% per year (95% CI: 5.1-7.0%).

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Risk factors associated with early post-ICH dementia (EPID) included location of hemorrhage (HR 2.04, 95% CI: 1.06-3.91, P=.02) and ICH volume (HR 1.47 per 10 mL increase, 95% CI: 1.09-1.97, P<.001). Risk factors identified for delayed post-ICH dementia (DPID) included a mood disorder diagnosis (HR 1.29, 95% CI: 1.02-1.63, P=.01), white matter disease on CT scan (HR 1.07, 95% CI: 1.07-2.71, P=.04), and education level (HR 0.60, 95% CI: 0.40-0.89, P<.001).

Interestingly, APOE ε2 variant appeared to be tied to EPID (HR 1.69, 95% CI 1.14-2.50, P=.009) whereas the APOE ε4 variant appeared to be tied to DIPD (HR 2.12, 95% CI: 1.45-3.09, P<.001).

The study was limited by a lack of in-person cognitive assessment; however the authors highlight that the telephone-based assessment has been shown to correlate with several in-person assessments including the Mini-Mental State Examination.

In an accompanying editorial, Rebecca Gottesman, MD, PhD, of the Department of Neurology at Johns Hopkins University in Baltimore, MD, noted that the results suggest that post-ICH cognitive decline could be underrecognized.

“The frequency of dementia reported in this study emphasizes that it may be helpful to routinely incorporate questions about cognitive status and functional recovery after ICH,” she wrote.


  1. Biffi A, Bailey D, Anderson CD, et al. Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage. JAMA Neurol. 2016; doi:10.1001/jamaneurol.2016.0955.
  2. Gottesman RF. Dementia After Intracerebral Hemorrhage. JAMA Neurol. 2016; doi:10.1001/jamaneurol.2016.1538.