Cerebrovascular Disease Linked to Alzheimer’s

Summary: Diseases blood vessels in the brain could contribute to the onset of Alzheimer’s disease, a new study reports.

Source: Rush University Medical Center.

Study finds association between diseases in brain blood vessels and dementia.

While strokes are known to increase risk for dementia, much less is known about diseases of large and small blood vessels in the brain, separate from stroke, and how they relate to dementia. Diseased blood vessels in the brain itself, which commonly is found in elderly people, may contribute more significantly to Alzheimer’s disease dementia than was previously believed, according to new study results published in June in The Lancet Neurology, a British medical journal.

“Cerebral vessel pathology might be an under-recognized risk factor for Alzheimer’s disease dementia,” the researchers wrote.

The study by researchers from the Rush Alzheimer’s Disease Center analyzed medical and pathologic data on 1,143 older individuals who had donated their brains for research upon their deaths, including 478 (42 percent) with Alzheimer’s disease dementia. Analyses of the brains showed that 445 (39 percent) of study participants had moderate to severe atherosclerosis — plaques in the larger arteries at the base of the brain obstructing blood flow — and 401 (35 percent) had brain arteriolosclerosis — in which there is stiffening or hardening of the smaller artery walls.

The study found that the worse the brain vessel diseases, the higher the chance of having dementia, which is usually attributed to Alzheimer’s disease. The increase was 20 to 30 percent for each level of worsening severity. The study also found that atherosclerosis and arteriolosclerosis are associated with lower levels of thinking abilities, including in memory and other thinking skills, and these associations were present in persons with and without dementia.

“Both large and small vessel diseases have effects on dementia and thinking abilities, independently of one another, and independently of the common causes of dementia such as Alzheimer’s pathology and strokes,” said Dr. Zoe Arvanitakis. A neurologist and researcher at the Rush Alzheimer’s Disease Center, Arvanitakis led the study, which was funded by the National Institutes of Health.

Part of Rush University Medical Center, the Rush Alzheimer’s Disease Center is dedicated to the study of Alzheimer’s, a neurological condition that is the most common cause of dementia. It is one of 29 designated centers in the United States funded by the National Institute on Aging.

The study was not designed to determine causation of Alzheimer’s dementia, or even whether vascular disease or Alzheimer’s developed first. “But it does suggest that vessel disease plays a role in dementia,” Arvanitakis said. “We found that blood vessel diseases are very common in the brain, and are associated with dementia that is typically attributed to Alzheimer’s disease during life.”

Does preventing cerebrovascular disease also prevent Alzheimer’s?

The study examined which cognitive difficulties are caused by vessel diseases and whether vessel disease and Alzheimer’s are more destructive in tandem than they would be alone. An editorial in The Lancet Neurology that accompanied the study findings noted that while other studies have indicated that proactive measures like eating a selective diet and getting regular exercise might protect people against getting Alzheimer’s, those interventions might actually be acting on non-Alzheimer’s disease processes, such as cerebrovascular disease.

Image shows neurons.
The study found that the worse the brain vessel diseases, the higher the chance of having dementia, which is usually attributed to Alzheimer’s disease. NeuroscienceNews.com image is adapted from the Rush University press release.

Arvanitakis says they don’t know yet. “They may decrease actual Alzheimer’s, and possibly even work by yet other pathways,” Arvanitakis said. “We hope to better distinguish how the clinical expression of vessel diseases in the brain differ from those of Alzheimer’s, so that we may eventually use earlier and more targeted treatments for dementia.”

Nearly 47 million people now live with dementia worldwide, according Alzheimer’s Disease International, the international federation of Alzheimer associations around the world. By 2050, that number is projected to be 132 million. Therefore, finding ways to treat or prevent the disease “is a major goal,” Arvanitakis said.

About this Alzheimer’s disease research article

The participants in the study published in Lancet Neurology came from two (RADC) cohort studies, the Religious Orders Study and the Rush Memory and Aging Project, which have followed people older than 65, in their communities, for more than two decades. Participants receive annual health assessments and agree to donate their brains for research upon their deaths. The Lancet Neurology study used clinical data gathered from participants from 1994 to 2015, and pathologic data obtained from examination of the brains donated for autopsy, and used regression analyses to determine the odds of Alzheimer’s dementia and levels of cognitive function, for increasing levels of brain vessel diseases.

Source: Rush University Medical Center
Image Source: This NeuroscienceNews.com image is adapted from the Rush University press release.
Original Research: Abstract for “Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study” by Zoe Arvanitakis, Ana W Capuano, Sue E Leurgans, David A Bennett, and Julie A Schneider in Lancet Neurology. Published online June 13 2016 doi:10.1016/S1474-4422(16)30029-1

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Rush University Medical Center. “Cerebrovascular Disease Linked to Alzheimer’s.” NeuroscienceNews. NeuroscienceNews, 5 July 2016.
<https://neurosciencenews.com/alzheimers-cerebrovascular-disease-4613/>.[/cbtab][cbtab title=”APA”]Rush University Medical Center. (2016, July 5). Cerebrovascular Disease Linked to Alzheimer’s. NeuroscienceNews. Retrieved July 5, 2016 from https://neurosciencenews.com/alzheimers-cerebrovascular-disease-4613/[/cbtab][cbtab title=”Chicago”]Rush University Medical Center. “Cerebrovascular Disease Linked to Alzheimer’s.” https://neurosciencenews.com/alzheimers-cerebrovascular-disease-4613/ (accessed July 5, 2016).[/cbtab][/cbtabs]


Abstract

Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study

Background
Few data on the pathology of cerebral vessel disease, dementia, and cognition are available. We examined the association of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer’s disease dementia and cognitive function.

Methods
This cross-sectional study included men and women aged 65 years or older who had yearly clinical assessments and had agreed to brain autopsy at the time of death, as part of one of two cohort studies of ageing (The Religious Orders Study and the Rush Memory and Aging Project). Individuals without dementia or with Alzheimer’s disease dementia, and with complete neuropathological data, are included in our analyses. We used neuropsychological data proximate to death to create summary measures of global cognition and cognitive domains. Clinical data recorded between 1994 and 2015 were used to determine presence of Alzheimer’s disease dementia. Systematic neuropathological assessments documented the severity of cerebral large vessel (atherosclerosis) and small vessel (arteriolosclerosis) disease. By use of regression analyses adjusted for demographics, gross and microscopic infarcts, and Alzheimer’s disease pathology, we examined associations of vessel disease severity (mild, moderate, and severe) with odds of probable and possible Alzheimer’s disease dementia and cognitive function.

Findings

Study enrolment began in January, 1994, and two cohort studies are ongoing. 1143 individuals were included in our analyses (median age at death 88·8 years; 478 [42%] with Alzheimer’s disease dementia). Moderate-to-severe atherosclerosis was present in 445 (39%) individuals, and arteriolosclerosis in 401 (35%) individuals. Each level increase in the severity of atherosclerosis or arteriolosclerosis was associated with significantly higher odds of Alzheimer’s disease dementia (odds ratio [OR] for atherosclerosis 1·33, 95% CI 1·11–1·58; OR for arteriolosclerosis 1·20, 1·04–1·40). Atherosclerosis was associated with lower scores for global cognition (estimate −0·10 [SE 0·04], p=0·0096) and four cognitive domains (episodic memory −0·10 [0·04], p=0·017; semantic memory −0·11 [0·05], p=0·018; perceptual speed −0·14 [0·04], p=0·00080; and visuospatial abilities −0·13 [0·04], p=0·0080), but not working memory (−0·05 [0·04], p=0·21). Arteriolosclerosis was associated with lower scores for global cognition (estimate −0·10 [0·03], p=0·0015) and four domains (episodic memory −0·12 [0·04], p=0·00090; semantic memory −0·10 [0·04], p=0·013; working memory −0·07 [0·03], p=0·045; perceptual speed −0·12 [0·04], p=0·0012), and a non-significant association was noted for visuospatial abilities (−0·07 [0·03], p=0·052). Findings were unchanged in analyses controlling for the presence of APOE ε4 allele or vascular risk factors.

Interpretation
Cerebral atherosclerosis and arteriolosclerosis are associated with Alzheimer’s disease dementia, and are also associated with low scores in most cognitive domains. Cerebral vessel pathology might be an under-recognised risk factor for Alzheimer’s disease dementia.

Funding
US National Institutes of Health.

“Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study” by Zoe Arvanitakis, Ana W Capuano, Sue E Leurgans, David A Bennett, and Julie A Schneider in Lancet Neurology. Published online June 13 2016 doi:10.1016/S1474-4422(16)30029-1

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