Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage

Abstract

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 PARTICIPANTSA 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.

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“…Biffi et al [33] report a high incidence of dementia (5.8% per year), which could be an overestimation, perhaps through the use of TICS-m rather than in-person assessment, although the concordance between telephone and in-person assessments was high. Despite this, it is clear that cognitive impairment or dementia following ICH is under-recognized.…”

“…One recent study sought to establish whether different factors were associated with early ( 6 months) or delayed (>6 months) dementia following ICH [33]. Dementia diagnosis was based on International Classification of Diseases-9 (ICD-9) codes established from electronic medical records and/or modified Telephone Interview for Cognitive Status (TICS-m) scores <20.…”

“…Of the 738 people with ICH recruited, 279 (37.8%) developed dementia during the median follow-up of 47.4 months; 140 patients developed dementia within 6 months, with the remaining 139 being diagnosed more than 6 months post-ICH. Risk factors for early and delayed dementia after ICH varied significantly [33]. ICH volume, lobar location and presence of 1 copy of apolipoprotein E (APOE) ε2 were associated with early dementia but not delayed dementia.…”

“…The APOE ε2 variant has been reported to be associated with larger haematoma volumes and/or expansion and therefore poor functional outcome at 90 days [34,35]. Conversely, educational level, pre-morbid mood disturbance, imaging markers of SVD [white matter disease on computed tomography (CT) and cerebral microbleeds (CMB)] and presence of 1 copy of APOE ε4 were associated with delayed but not early dementia [33].…”

“…Despite this, it is clear that cognitive impairment or dementia following ICH is under-recognized. In summary, ICH characteristics were associated with early and not late dementia after ICH, and markers associated with both SVD and late-onset AD were associated with delayed onset dementia [33]. Further Increased volume of stroke lesion [195] Early post-stroke complications [196] Seizure Delirium Hypoxia Hypotension…”