After Hemorrhagic Stroke, Patients at High Risk of Early and Delayed Dementia Interview with:

Alessandro Biffi, MD Behavioral Neurology and Neuropsychiatry Departments of Neurology and Psychiatry Massachusetts General Hospital / Harvard Medical School

Dr. Alessandro Biffi

Alessandro Biffi, MD
Behavioral Neurology and Neuropsychiatry
Departments of Neurology and Psychiatry
Massachusetts General Hospital / Harvard Medical School What is the background for this study?

Dr. Biffi: Intracerebral Hemorrhage (ICH) is the most severe form of stroke. It is a form of hemorrhagic (i.e. bleeding) stroke that accounts for ~ 15% of all acute cerebrovascular conditions, affecting ~ 70,000 Americans every year. However, because of its severity it is responsible for almost half of all stroke-related disability worldwide. Survivors of ICH are at very high risk for cognitive impairment (up to and including dementia) following the acute cerebral bleeding event. However, we possess very limited understanding of the time dynamics and risk factors for post-ICH dementia. In particular, prior to our study it was unclear whether the acute cerebral injury due to ICH would be the only mechanism potentially responsible for subsequent development of dementia.

This question is motivated by prior observations suggesting that Intracerebral Hemorrhage represents the acute manifestation of cerebral small vessel disease, a progressive degenerative disorder of small caliber arteries of the central nervous system.

There exist two major subtypes of small vessel disease:

1) cerebral amyloid angiopathy, caused by the deposition of a toxic protein product, beta-amyloid, in the blood vessels (in a process similar to the formation of beta-amyloid plaques that cause Alzheimer’s disease);

2) arteriolosclerosis, caused by long-standing elevated blood pressure. ICH survivors have been previously shown to harbor very severe small vessel disease, which has been linked to dementia in patients without cerebral bleeding.

Our hypothesis was that early-onset dementia (occurring in the first 6 months after ICH) is a manifestation of the acute neurological damage associated with cerebral bleeding, whereas delayed onset dementia (developing beyond 6 months from the acute ICH event) is associated with known markers of small vessel disease, including imaging findings on CT/MRI and genetic markers (such as the APOE gene). What are the main findings?

Response: We studied 738 survivors of Intracerebral Hemorrhage cared for at Massachusetts General Hospital in Boston from 2006 to 2013, all of which had no history of cognitive impairment before their hemorrhagic stroke. Of these, 140 were diagnosed with dementia within 6 months of ICH (representing about 19% of the overall study population), thus representing the early-onset dementia group. An additional 139 patients developed dementia beyond 6 months from the acute ICH, at a rate of approximately 6% every year. Therefore, in our study about half of the dementia diagnoses were formulated shortly after an hemorrhagic stroke, and the remaining half over a period of several months to years. Overall, a total of 279 ICH survivors in our study developed dementia, accounting for almost 40% of our study population.

We identified as risk factors for early-onset dementia after ICH the size of the bleeding (with larger bleeds being more likely to cause dementia); however, larger bleeds were not a risk factor for delayed dementia after ICH. Instead we found that the risk of developing dementia long after ICH was associated with known markers of small vessel disease, chiefly cerebral white matter disease. Lower educational level, African-American ancestry and having a mood disorder also increase risk for delayed post-ICH dementia. What should readers take away from your report?

Response: Patients suffering from Intracerebral Hemorrhage are at very high risk of developing dementia, and over half of these occur months to years after the initial stroke. Caregivers and clinicians should therefore be on the lookout for evidence of cognitive impairment in this very high-risk patient population. Patients themselves must receive adequate counseling on the risk of developing dementia following ICH and (pending further studies in this field) work with their doctors to control all the risk factors (high blood pressure, diabetes, smoking, exposure to alcohol and other toxins) that can affect cognitive health in general. What recommendations do you have for future research as a result of this study?

Response: We need additional studies focused on identifying risk factors and mechanisms for dementia following Intracerebral Hemorrhage, and in particular for delayed dementia – since it appears to account for half of all cognitive impairment cases among these patients. Specifically, future studies should focus on whether prevention of cerebral small vessel disease by controlling risk factors (mainly, blood pressure) can result in decreased risk of dementia after ICH. Furthermore, African-American patients appear to be at highest risk for delayed post-ICH dementia, and this disparity in outcome deserves additional investigation, looking for potential underlying biological explanations as well as tailored interventions. Thank you for your contribution to the community.


Alessandro Biffi, Destiny Bailey, Christopher D. Anderson, Alison M. Ayres, Edip M. Gurol, Steven M. Greenberg, Jonathan Rosand, Anand Viswanathan. Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage. JAMA Neurology, 2016; DOI: 10.1001/jamaneurol.2016.0955

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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