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Original Investigation
August 2016

Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage

Author Affiliations
  • 1Center for Human Genetic Research, Massachusetts General Hospital, Boston
  • 2J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston
  • 3Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts
  • 4Division of Stroke, Department of Neurology, Massachusetts General Hospital, Boston
  • 5Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston
  • 6Division of Behavioral Neurology, Department of Neurology, Massachusetts General Hospital, Boston
  • 7Division of Neuropsychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston
JAMA Neurol. 2016;73(8):969-976. doi:10.1001/jamaneurol.2016.0955

Importance  Patients who have experienced intracerebral hemorrhage (ICH) appear to develop cognitive impairment at high rates, both early after ICH and over the long term.

Objective  To identify and compare risk factors for early and delayed dementia after ICH.

Design, Setting, and Participants  A longitudinal study enrolled patients who had experienced ICH from January 1, 2006, to December 31, 2013. A total of 738 participants 18 years or older, without pre-ICH dementia, who presented to a tertiary care academic institution with primary ICH were included in the analyses of early post-ICH dementia (EPID). After accounting for incident dementia and mortality at 6 months, 435 participants were included in the analyses of delayed post-ICH dementia (DPID).

Exposures  Intracerebral hemorrhage.

Main Outcomes and Measures  Cognitive performance was captured using the modified Telephone Interview for Cognitive Status test. Outcomes included EPID, diagnosed within 6 months after ICH, and DPID, diagnosed beyond 6 months after ICH.

Results  Among 738 patients who had experienced ICH (mean [SD] age, 74.3 [12.1] years; 384 men [52.0%]), 140 (19.0%) developed dementia within 6 months. A total of 435 patients without dementia at 6 months were followed up longitudinally (median follow-up, 47.4 months; interquartile range, 43.4-52.1 months), with an estimated yearly incidence of dementia of 5.8% (95% CI, 5.1%-7.0%). Larger hematoma size (hazard ratio [HR], 1.47 per 10-mL increase; 95% CI, 1.09-1.97; P < .001 for heterogeneity) and lobar location of ICH (HR, 2.04; 95% CI, 1.06-3.91; P = .02 for heterogeneity) were associated with EPID but not with DPID. Educational level (HR, 0.60; 95% CI, 0.40-0.89; P < .001 for heterogeneity), incident mood symptoms (HR, 1.29; 95% CI, 1.02-1.63; P = .01 for heterogeneity), and white matter disease as defined via computed tomography (HR, 1.70; 95% CI, 1.07-2.71; P = .04 for heterogeneity) were associated with DPID but not EPID.

Conclusions and Relevance  Incident dementia early after ICH is strongly associated with hematoma size and location. Delayed incident dementia is frequent among patients who have experienced ICH and is not prominently associated with acute characteristics of ICH. These findings suggest the existence of heterogeneous biological mechanisms accounting for early vs delayed cognitive decline among patients who have experienced ICH.