Background: Dementia is a disease known to cause chronic deterioration of intellectual functions severe enough to interfere with the ability to perform activities of daily living. Alzheimer’s disease (AD) is the most frequent cause of dementia and is expected to have a substantial impact on the health care system as the Canadian population ages. Current therapies are ineffective at halting disease progression; thus, investigations examining risk factors for AD have become a popular avenue of research. A relationship between cerebrovascular disease and the risk of AD has been established, but the underlying mechanisms on how these morbidities are related remain unclear. The apolipoprotein E gene (ApoE) influences the development of AD with the apolipoprotein E-e4 allele (ApoE-e4) conferring increased risk. The underlying mechanism by which the ApoE-e4 allele influences AD is unclear. Since the ApoE-e4 allele is related to both AD and stroke, the impact of cerebral infarcts on AD may vary by ApoE-e4 allele status. Objective: The objective of this study was to assess if ApoE-e4 allele status modified the relationship between cerebral infarcts and AD. Methods: Secondary data from the Nun Study, a longitudinal clinico-pathologic study of aging representing 678 female participants 75+ years were used for this investigation. AD was diagnosed using criteria for clinical dementia and AD pathology. Dementia was diagnosed using standard criteria, including the Consortium to Establish a Registry for Alzheimer’s Disease battery of neuropsychological tests and performances on activities of daily living. AD pathology was diagnosed using a modified version of the National Institute on Aging and Reagan Institute criteria. Infarcts were identified during gross neuropathologic assessment at autopsy. Logistic regression was used to assess the relationship between AD and the presence, location, and size of cerebral infarcts. Regression models were then stratified by ApoE-e4 allele status to determine if this variable was a significant effect modifier. The relationship of ApoE-e4 allele status with AD, as well as presence of cerebral infarcts, was also explored. All regression models were adjusted for age at death, educational level, and, when appropriate, ApoE-e4 allele status. A sensitivity analysis using different definitions for the outcome AD was performed and showed that varying criteria for AD pathology did not change study results; however, the use of clinical dementia (regardless of pathology) as an outcome did produce significantly different results. Thus, the research questions were repeated using clinical dementia as an outcome. Results: The presence of cerebral infarcts was not significantly associated with AD; this relationship did not change when location and size of infarcts were examined. ApoE-e4 was significantly associated with an increased risk of AD. ApoE-e4 was not associated with presence of cerebral infarcts. ApoE-e4 did not modify the relationship between presence of cerebral infarcts and AD. When the outcome clinical dementia was investigated, presence of cerebral infarcts significantly increased the risk of dementia. This relationship remained when location and size of infarcts were analyzed. ApoE-e4 allele status slightly modified the relationship between presence of cerebral infarcts and dementia. Conclusions: The findings from this study suggest that individuals with severe AD pathology are unlikely to be affected by cerebral infarcts. Future studies should focus on examining levels of severity of AD pathology in relation to cerebral infarcts. Cerebral infarcts appear to have an impact on dementia and this relationship was found to slightly vary by ApoE-e4 status. Future studies are recommended to examine how ApoE interacts with a variety of age-related risk factors to increase the risk of AD.

Background: Dementia is a disease known to cause chronic deterioration of intellectual functions severe enough to interfere with the ability to perform activities of daily living. Alzheimer’s disease (AD) is the most frequent cause of dementia and is expected to have a substantial impact on the health care system as the Canadian population ages. Current therapies are ineffective at halting disease progression; thus, investigations examining risk factors for AD have become a popular avenue of research. A relationship between cerebrovascular disease and the risk of AD has been established, but the underlying mechanisms on how these morbidities are related remain unclear. The apolipoprotein E gene (ApoE) influences the development of AD with the apolipoprotein E-e4 allele (ApoE-e4) conferring increased risk. The underlying mechanism by which the ApoE-e4 allele influences AD is unclear. Since the ApoE-e4 allele is related to both AD and stroke, the impact of cerebral infarcts on AD may vary by ApoE-e4 allele status. Objective: The objective of this study was to assess if ApoE-e4 allele status modified the relationship between cerebral infarcts and AD. Methods: Secondary data from the Nun Study, a longitudinal clinico-pathologic study of aging representing 678 female participants 75+ years were used for this investigation. AD was diagnosed using criteria for clinical dementia and AD pathology. Dementia was diagnosed using standard criteria, including the Consortium to Establish a Registry for Alzheimer’s Disease battery of neuropsychological tests and performances on activities of daily living. AD pathology was diagnosed using a modified version of the National Institute on Aging and Reagan Institute criteria. Infarcts were identified during gross neuropathologic assessment at autopsy. Logistic regression was used to assess the relationship between AD and the presence, location, and size of cerebral infarcts. Regression models were then stratified by ApoE-e4 allele status to determine if this variable was a significant effect modifier. The relationship of ApoE-e4 allele status with AD, as well as presence of cerebral infarcts, was also explored. All regression models were adjusted for age at death, educational level, and, when appropriate, ApoE-e4 allele status. A sensitivity analysis using different definitions for the outcome AD was performed and showed that varying criteria for AD pathology did not change study results; however, the use of clinical dementia (regardless of pathology) as an outcome did produce significantly different results. Thus, the research questions were repeated using clinical dementia as an outcome. Results: The presence of cerebral infarcts was not significantly associated with AD; this relationship did not change when location and size of infarcts were examined. ApoE-e4 was significantly associated with an increased risk of AD. ApoE-e4 was not associated with presence of cerebral infarcts. ApoE-e4 did not modify the relationship between presence of cerebral infarcts and AD. When the outcome clinical dementia was investigated, presence of cerebral infarcts significantly increased the risk of dementia. This relationship remained when location and size of infarcts were analyzed. ApoE-e4 allele status slightly modified the relationship between presence of cerebral infarcts and dementia. Conclusions: The findings from this study suggest that individuals with severe AD pathology are unlikely to be affected by cerebral infarcts. Future studies should focus on examining levels of severity of AD pathology in relation to cerebral infarcts. Cerebral infarcts appear to have an impact on dementia and this relationship was found to slightly vary by ApoE-e4 status. Future studies are recommended to examine how ApoE interacts with a variety of age-related risk factors to increase the risk of AD.

Background: Patients with carotid artery dissection (CAD) have been reported to have different vascular risk factor profiles and clinical outcomes to those with vertebral artery dissection (VAD). However, there are limited data from recent, large international studies comparing risk factors and clinical features in patients with cervical artery dissection (CeAD) with other TIA or ischemic stroke (IS) patients of similar age and sex. Methods: We analysed demographic, clinical and risk factor profiles in TIA and IS patients ≤ 55 years of age with and without CeAD in the large European, multi-centre, Stroke In young FAbry Patients 1 (sifap1) study. Patients were further categorised according to age (younger: 18–44 years; middle-aged: 45–55 years), sex, and site of dissection. Results: Data on the presence of dissection were available in 4,208 TIA and IS patients of whom 439 (10.4%) had CeAD: 196 (50.1%) had CAD, 195 (49.9%) had VAD, and 48 had multiple artery dissections or no information regarding the dissected artery. The prevalence of CAD was higher in women than in men (5.9 vs. 3.8%, p < 0.01), whereas the prevalence of VAD was similar in women and men (4.6 vs. 4.7%, n.s.). Patients with VAD were younger than patients with CAD (median = 41 years (IQR = 35–47 years) versus median = 45 years (IQR = 39–49 years); p < 0.01). At stroke onset, about twice as many patients with either CAD (54.0 vs. 23.1%, p < 0.001) or VAD (63.4 vs. 36.6%, p < 0.001) had headache than patients without CeAD and stroke in the anterior or posterior circulation, respectively. Compared to patients without CeAD, hypertension, concomitant cardiovascular diseases and a patent foramen ovale were significantly less prevalent in both CAD and VAD patients, whereas tobacco smoking, physical inactivity, obesity and a family history of cerebrovascular diseases were found less frequently in CAD patients, but not in VAD patients. A history of migraine was observed at a similar frequency in patients with CAD (31%), VAD (27.8%) and in those without CeAD (25.8%). Conclusions: We identified clinical features and risk factor profiles that are specific to young patients with CeAD, and to subgroups with either CAD or VAD compared to patients without CeAD. Therefore, our data support the concept that certain vascular risk factors differentially affect the risk of CAD and VAD.