The Overlap Between Vascular Disease and Alzheimer's Disease

The flexibility and structural integrity of blood vessel networks declines with age. Metabolic waste products accumulate in blood vessel walls, and separately a combination of damaged cells, damaged proteins, and chronic inflammation leads to harmful restructuring. Other mechanisms are at work also, such as those involved in hypertension. This all means that ever more tiny blood vessels fail in one way or another, either bleeding into brain tissue or not delivering oxygen efficiently. The resulting damage builds up, a bit at a time. Thus there is every reason to consider a causal link between vascular issues and forms of dementia such as Alzheimer's: vascular problems eating away at the brain's integrity are going to worsen the effects of an emerging dementia even if it is caused by entirely different mechanisms. Further, there is the possibility that issues with blood flow in the brain can directly impact clearance of the misfolded proteins called amyloids implicated in the progression of Alzheimer's disease. Other links may yet be discovered.

The interaction between cerebrovascular disease (CVD) and Alzheimer's disease (AD) is a topic of considerable current interest. With age there is an increasing prevalence of coincident AD and CVD that is well recognized. Since 50% to 84% of the brains of persons who die aged 80 to 90+ show appreciable cerebrovascular lesions (CVL), a specific problem is their impact in relation to AD pathology. CVD frequently occurs in brains of both non-demented elderly and AD patients. The burden of vascular and AD-type pathologies are leading and independent causes of dementia in the elderly, suggesting additive or synergistic effects of both types of lesions on cognitive impairment.

The most frequent vascular pathologies in the aging brain and in AD are cerebral amyloid angiopathy and small vessel disease. AD brains with minor CVD, similar to pure vascular dementia, show subcortical vascular lesions in about two-thirds, while in mixed type dementia (AD plus vascular dementia), multiple larger infarcts are more frequent. Small infarcts in patients with full-blown AD have no impact on cognitive decline but are overwhelmed by the severity of Alzheimer pathology, while in early stages of AD, cerebrovascular lesions may influence and promote cognitive impairment, lowering the threshold for clinically overt dementia.

Link: http://dx.doi.org/10.1186/s12916-014-0206-2

Comments

Slightly off-topic, but - Reading through your linked articles, I eventually arrived at the SENS page describing GlycoSENS, in which Michael Rae refers to the Ending Aging book.

Has anyone involved with SENS broached the subject of printing a second edition that's been updated with discoveries and advances since the first print?

I feel like a reprint that highlights progress could do much to advance the cause.

Posted by: Seth at November 14th, 2014 11:19 AM

Hi Seth,

First, there already IS a second edition ;) . The paperback contains an Afterword, which gives major updates up through 2008.

We've bandied about the idea of doing THIRD ;) and more thoroughly revised and updated version a few times, but have so far decided against it: it is such an investment of time and thought to do a true revision, and of course it's then outdated not long after you release it once again.

Equally, if conversely, it's also true that while there has certainly been a lot of exciting progress since we first released the book, the core of the platform hasn't changed, and the long-term plan remains the same – it's just the details of which branches in the path have opened or been weeded over. Moreover, we still encounter a surprising number of people who support our mission to apply regenerative medicine to the diseases and disabilities of aging and yet haven't even read the first edition, so there is a lot more lack of information about the core of the plan than the up-to-date details and immediate next steps.

And, progress will only really take off once there is a more serious investment — financial, societal, and in human capital — into rejuvenation research, so the bottom line of the book remains the same: humanity desperately needs to wake up to the immediate daily crisis of death and disease brought to us daily by the degenerative aging process, and to the civilizational threat that global demographic aging will entail if we don't start making those commitments post haste.

Posted by: Michael at November 14th, 2014 1:05 PM
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