"Curiouser and Curiouser:"
The increasingly complex relationship of Cardiovascular Disease and Dementia.
"Curiouser and curiouser!" Cried Alice (she was so much surprised, that for the moment she quite forgot how to speak good English).- Alice's Adventures in Wonderland, Lewis Carroll, 1865
It used to be so easy. If a person had a heavy burden of cardiovascular, and hence cerebrovascular, risk factors and then developed dementia, multi-infarct dementia could be readily assumed to be the cause. However, a growing body of evidence, including numerous presentations from the more than 5000 attendees at the July 2011 Alzheimer's Association International Conference in Paris, points to an important role for vascular risk factors in increasing risk for Alzheimer's disease, independent of their role for stroke.
Among dozens of papers that addressed the topic, Emmanuelle Duron and colleagues from Broca Hospital in Paris [Poster P2-130] found that metabolic syndrome was twice almost as frequent in patients with AD (17%) than in healthy controls (9%). Similarly, Charles Bernick and investigators from the Cardiovascular Health Study's Cognition Study [Poster P2-120] showed that markers of peripheral vascular disease, such as ankle-arm index and coronary calcium score were associated with accelerated progression to AD among 445 subjects who were not demented at the beginning of the 7 year study. Although the reasons for the faster progression remain unclear, Natalie Marchant from UC-Berkeley [Presentation F2-02-04] provided a hint in her report that vascular risk factors (but not strokes) led to increased cerebral deposition of the beta amyloid peptide responsible for Alzheimer plaques. Another possibility emerges from data presented by Schantel Williams from NYU [Poster P1-488], who reported that hypertension itself is associated with poorer performance in cognitive domains like attention and working memory that predict AD. Thus, the hypertension may act to step the clock forward for AD and lead to an earlier onset of symptoms.
However, several papers found limited effects of hypertension on AD risk. One possibility, addressed by Carole Dufouil and a team from the French INSERM research institute [Presentation S1-03-06], is that the duration of hypertension is the key factor. Other confounding factors include the relationships between lifestyle, general health, and genetic factors. For example, Denise Head and colleagues from Washington University in St. Louis [Poster P1-377], found that sedentary lifestyle and Apolipoprotein E genotype influenced Alzheimer risk. Of course, sedentary lifestyle is itself associated with hypertension. Therefore, it might not be the vascular risk factors themselves that increase AD risk, but rather a common origin of both vascular and Alzheimer risks. That possibility was supported by a presentation by Manuela Padurariu from Romania [Poster P2-056] illustrating that hypertension was more likely to be observed in patients with mild cognitive impairment and Alzheimer's disease than in controls, but total cholesterol levels were lower.
The new information from the 2011 Alzheimer's conference probably won't lead to major changes in how practicing clinicians approach treatment of cardiovascular risk factors. However, it may be useful to add Alzheimer's disease risk reduction to the list of benefits from early intervention and good adherence to treatment plans for patients with the well-recognized risk factors for cardiovascular disease.
Abstracts for these presentations are published in Alzheimer's and Dementia 2011;7 (4) Suppl. 1.