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. 2013 May 23;16(3):88. doi: 10.1136/eb-2013-101292

Alzheimer's disease is associated with increased risk of haemorrhagic stroke

PMCID: PMC13421621  PMID: 23704703

Question

Question: Are community-dwelling people with Alzheimer's disease at increased risk of stroke, and is there a difference by type of stroke?

People: All 28 093 community-dwelling adults with Alzheimer's disease living in Finland on 31 December 2005, who were each matched to a person without Alzheimer's disease by age, sex and region of residence (total n=56 186; mean age 79.6 years; 67.8% were female; age range 42–101). People with strokes prior to 1 January 2006 or to their Alzheimer's diagnosis were excluded along with their matched controls, as were pairs where the matched controls had been entitled to reimbursed Alzheimer's medication before enrolment. This left 25 404 pairs of individuals for analysis. Individuals in the control group who developed Alzheimer's during follow-up (1766 people) were included in the Alzheimer's group from the date of diagnosis.

Setting: Finland; December 2005–December 2009.

Risk factors: Diagnosis of Alzheimer's disease was based on National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria. People with Alzheimer's disease were identified from national prescription and reimbursement registers that were linked to a statutory register (HILMO) containing information on the use of inpatient and outpatient healthcare services in Finland. Analyses were adjusted for cancer, diabetes and cardiovascular disease. Associations were investigated by: age at follow-up (<75, 75–79, 80–85 and ≥86 years); quartiles of approximate age at diagnosis (calculated from the diagnosis of Alzheimer's disease or first reimbursement purchase of Alzheimer's medication, depending on which occurred first).

Outcomes: The three main outcomes of interest were: incidence of all strokes due to haemorrhage or cerebral infarction (International Classification of Diseases (ICD)-10 classification I60–I64); incidence of ischaemic strokes (I63); incidence of haemorrhagic strokes (I60–I62). Strokes were identified from the HILMO statutory register.

Methods

Design: Cohort study.

Follow-up period: 4 years.

Main results

There were 2947 incident strokes during follow-up. Of these 2414 (82%) were ischaemic strokes, 516 (17.5%) were haemorrhagic and 17 (0.6%) had unclear aetiology. Alzheimer's disease was not associated with an increased overall risk of stroke (adjusted HR 1.02, 95% CI 0.94 to 1.10) or of ischaemic stroke (adjusted HR 0.93, 95% CI 0.86 to 1.01). However, Alzheimer's disease was associated with an increased risk of haemorrhagic stroke (adjusted HR 1.34, 95% CI 1.12 to 1.61). In the analysis by age at follow-up, Alzheimer's disease was associated with significantly higher overall risk of stroke in the youngest age group (>75 years, HR 1.42, 95% CI 1.12 to 1.80), but not for people in older age groups (80–85 and <85 years) when compared to people without Alzheimer's disease. In the analysis by age at diagnosis, compared to people without Alzheimer's, the risk of strokes was highest among people who were the youngest (38.9–73.9 years) when they were diagnosed with Alzheimer's (all stroke: adjusted HR 1.41, 95% CI 1.16 to 1.71; ischaemic stroke: adjusted HR 1.63, 95% CI 1.08 to 2.45; haemorrhagic stroke: adjusted HR 1.29, 95% CI 1.03 to 1.62).

Conclusions

People with Alzheimer's disease are at increased risk of haemorrhagic stroke but not ischaemic stroke compared to people without disease. Compared to people without Alzheimer's, the risk of any stroke appears higher among younger people with Alzheimer's disease.

Abstracted from:

Tolppanen AM, Lavikainen P, Solomon A, et al. Incidence of stroke in people with Alzheimer disease: a national register-based approach. Neurology 2013; 80: 353– 8.

Footnotes

Sources of funding: University of Eastern Finland.

Evid Based Ment Health. 2013 May 23;16(3):88.

Commentary

Jonathan Stone 1, Jack C De La Torre 2

A large body of evidence from epidemiological and neuroimaging studies indicates that vascular factors contribute strongly to age-related cognitive decline and Alzheimer's disease. Vascular risk factors (VRF) for dementia, including hypertension, atherosclerosis and type 2 diabetes, are also risk factors for ischaemic and haemorrhagic stroke, raising the question of whether sporadic Alzheimer's disease (usually considered distinct from stroke-induced vascular dementia) also has a vascular basis?

Tolppanen and colleagues address a question that can be seen as abstruse, but makes a significant contribution to the question: do individuals with a diagnosis of Alzheimer's disease have a raised risk of stroke? Their findings indicate an increased risk for haemorrhagic stroke but not for ischaemic stroke. As the authors note, their question is the converse of a question more often asked: do people with a history of stroke have a raised risk of dementia? The evidence indicates that they do.

The strengths of the paper include (1) a huge cohort from a single register of a relatively homogeneous Finnish population and (2) a careful differentiation of questions, and some provocative answers. The study also has weaknesses, particularly the lack of data on ApoE4, the most common genetic risk factor for late-onset sporadic Alzheimer's disease, and on cerebral amyloid angiopathy, found postmortem in about 80% of cases of Alzheimer's disease. Either condition can increase the chances of haemorrhagic stroke.

The importance of the present study is both scientific and clinical. Scientifically, it adds to the case for revisiting the view, which goes back to Alzheimer's first publication on the dementia which now bears his name, that age-related dementia is not vascular in origin, but a distinctive disease. Clinically, it may hasten the testing of vascular-targeted therapies to prevent, delay and treat this still-intractable dementia. Amyloid-targeted therapies for Alzheimer's disease are failing; risk factor analyses implicate vascular involvement; the millions already afflicted, and the millions who will soon be afflicted, need effective therapy. This study adds significantly to the case for the clinical testing of a new, vascular-focused approach.

Footnotes

Correspondence to: Dr Jonathan Stone, Professor of Retinal and Cerebral Neurobiology, Director, Bosch Institute, Save Sight Institute and Discipline of Physiology, University of Sydney F13, NSW 2006 Australia

Competing interests: None.

Articles from Evidence-Based Mental Health are provided here courtesy of BMJ Publishing Group

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