Late Dementia After ICH a 'Critical Issue'

June 28, 2016

Dementia that develops early after an intracerebral hemorrhage (ICH) is directly related to the size and location of the bleed, but dementia also develops in many patients much later, a new study shows, and this appears to be due to a different mechanism, possibly the underlying disease process itself.

"We think we are dealing with two different mechanisms when it comes to dementia following ICH. It is not just the hemorrhage itself that is causing the problem," lead author, Alessandro Biffi, MD, Massachusetts General Hospital, Boston, told Medscape Medical News.

"Dementia prevention efforts need to be increased in ICH patients," he said. "Ideally we need new therapies to target the underlying disease process — the degeneration of the microscopic vessels in the brain. This is an active area of research. But in the meantime, patients and their carers need to be made aware that there is a high risk of developing dementia in the next few years after an ICH."

Patients should be advised to follow generic interventions to maintain cognitive health, such as healthy diet and social and cognitive stimulation, he added. "And while we don't have definite data, I would argue that close control of blood pressure in patients who have had an ICH is recommended to reduce recurrent hemorrhage and reduce the risk of later dementia."

The results were published online in JAMA Neurology on June 13.

The analysis involved 738 patients (mean age, 74 years) without pre-ICH dementia, who presented to a tertiary care academic institution with primary ICH and were included in the analyses of early post-ICH dementia (within 6 months of the event). After accounting for incident dementia and mortality at 6 months, 435 participants were included in the analyses of delayed post-ICH dementia.

For assessments of both early and late dementia, cognitive performance was measured by using the modified Telephone Interview for Cognitive Status test.

Results showed that 140 of the 738 patients (19%) developed dementia within 6 months of the ICH. The 435 patients without dementia at 6 months were followed up longitudinally for a median of 47.4 months, with an estimated yearly incidence of dementia of 5.8%.

Factors significantly associated with early dementia were larger hematoma size (hazard ratio [HR], 1.47 per 10-mL increase) and lobar location of ICH (HR, 2.04). However, these two factors were not associated with delayed dementia. Rather, delayed dementia correlated with educational level (HR, 0.60), incident mood symptoms (HR, 1.29), and white matter disease as defined via computed tomography (HR, 1.70).

"Our findings showing a higher risk of early dementia with larger bleeds and if the bleed occurred in the cortical area of the brain make sense and are to be expected. But they have not been shown in quite such detail before," Dr Biffi commented. "What we don't know is whether the hemorrhage directly causes the dementia or if it is the tipping point of the underlying process."

He added: "We clearly show that dementia often develops later after ICH. Even patients not cognitively compromised in the short term have an increased risk of developing dementia long term. Of the 40% of patients who developed dementia in our study, it occurred in the first 6 months in only half of them."

Dr Biffi estimates that after the acute phase, dementia develops in 5% to 6% of patients with ICH each year. "That is much higher than in the normal population of similar age, in which the rate is around 1% to 3% per year. The question is, why?"

He believes it is the disease process responsible for the ICH that also causes the longer-term dementia.

"It is thought that ICH normally occurs as a result of degeneration of microscopic blood vessels in the brain (cerebral small-vessel disease)," he said. "We identified several markers which are associated with cerebral small-vessel disease and with an increased risk of delayed dementia after ICH. These include APOE ε4, white matter disease, and cerebral microbleeds. This suggests that the underlying degenerative process that is responsible for ICH is also responsible for the delayed dementia."

The authors conclude that their findings have "immediate clinical relevance" to healthcare professionals and patients with ICH.

"Assuming replication of our findings in future studies, adequate communication of the risk of cognitive decline (especially beyond the immediate period after ICH) will represent a critical issue for physicians, their patients who have experienced ICH, and patients' family and caregivers," they write.

β-Amyloid the Culprit?

In an accompanying editorial, Rebecca F. Gottesman, MD, PhD, from Johns Hopkins University, Baltimore, Maryland, points out that lobar microbleeds and the APOE ε4 allele are both associated with cerebral amyloid angiopathy — the deposition of β-amyloid in the small and mid-sized arteries in the brain — suggesting this may well be the cause of the hemorrhage and the delayed dementia.

She agrees with Dr Biffi and colleagues that more emphasis needs to be focused on cognitive function after ICH.

"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 concludes.

This study was supported by the US National Institutes of Health. The authors have disclosed no relevant financial relationships.

JAMA Neurol. Published online June 13, 2016. Abstract Editorial 

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