Eric wrote: If you have any real research about dementia though, please send. I will read it for sure.
My choice for atorvastatin is based on my doctor's recommendation, the apparent safety and efficacy numbers and my own results. It gets my numbers down into a good range and I have a clear coronary artery scan, so from a cardiac standpoint, I feel fairly confident about avoiding major issues.
As for brain health, it's much harder to know! I am a strong believer in lifestyle, environmental and judicious supplement choices for prevention or amelioration of risk, although I'm far from perfect in my habits. I take 500 mcg of methylcobalamin, recommended by the Generation Study Site Doctor to bring my levels above 500. I also take 2000 mg of Vitamin D3 daily to get that above 50, which seems to be important to brain health. (Don't have the citation at my finger tips.)
I also think clinical trials are a necessary path to expand knowledge of mechanisms of pathology, development of blood-based biomarkers to reduce the need for PET scans and MRI for clinical diagnosis, and determination of the efficacy of numerous "novel targets" for prevention and therapeutic treatment. I was in the Generations I clinical trial of people with ApoE 4/4 for two years. It involved a double-blind, randomized (32% placebo vs 68% CNP520 pill) study of a BACE-1 inhibitor of abnormal cleaving of the amyloid precursor protein. I will find out in early summer if I was on CNP520 or placebo, but was shown various test results early this month that confirmed my cognitive skills had not changed over the trial period. Which also means that I couldn't draw before and still can't, but have decent verbal skills!
Since you have MCI, and asked for "real research about dementia", I'll copy a few things that seem relevant to those of us with ApoE 4/4, who are likely to have elevated amyloid beta, considered to be a key biomarker signifying 'preclinical Alzheimer's disease". Like coronary plaques signifying preclinical heart disease, they are neither necessary nor sufficient for dementia, but seem to me to be a clear canary in the coal mine of increased risk.
This is from a February 2020 paper in the journal Aging
, studying "association of job demand-control combinations with dementia, ...APOE ɛ4 and work duration... A total of 2,579 dementia-free individuals aged 60+ years from Sweden were followed over 12 years." Here are their encouraging result for someone with a Ph.D in economics:
The role of Apolipoprotein E epsilon4 in the association between psychosocial working conditions and dementia
...it has been shown that education, job complexity, leisure activities, and social network may attenuate the genetic risk of dementia due to APOE ɛ4 , possibly by enhancing cognitive reserve and reducing stress levels. Similarly, in this study, active jobs appeared to nullify the detrimental effect of genetic predisposition, as the risk of dementia among APOE ɛ4 carriers with active jobs was similar to that of the non-APOE ɛ4 carriers with active jobs.
If you are interested in clinical studies directly targeting intervention in people with MCI, this is from the 2018 CTAD (Clinical Trials for Alzheimer's Disease) conference, with a report on tramiprosate, an anti-amyloid drug that specifically targets amyloid beta oligomers, not the monomers targeted in earlier anti-amyloid trials. Here is the link, with the topic title, and an excerpt: CLINICAL BENEFITS OF TRAMIPROSATE IN ALZHEIMER’S DISEASE ARE ASSOCIATED WITH HIGHER NUMBER OF APOE4 ALLELES: THE “APOE4 GENE-DOSE EFFECT”
Results: Highest efficacy was observed in APOE4/4 homozygotes receiving 150 mg BID of tramiprosate, showing statistically significant effects on ADAS-cog and positive trends on CDR-SB (respectively, 40-66% and 25-45% benefit compared to placebo). APOE4 heterozygotes showed intermediate efficacy, and non-carriers showed no benefit. In 426 patients with MRI scans, no cases of treatment-emergent vasogenic edema were observed. In the three subgroups, the most common adverse events were nausea, vomiting, and decreased weight.
Conclusions: The “APOE4 Gene-Dose effect” is likely explained by the high prevalence of amyloid pathology in symptomatic APOE4 carriers. In APOE4/4 Alzheimer’s disease patients, the high dose of tramiprosate showed favorable safety and clinically meaningful efficacy in addition to standard of care.
This isn't research, but it is a link to a summary of the development of ALZ-801. the current
trial drug for tramiprosate, that includes a link to the company website and the NIH Clnical Trials. gov website. https://www.alzforum.org/therapeutics/alz-801
Here's a February 2020 summary of an adopted 2018 revised framework to guide research (not clinical practice) in diagnosing and studying Alzheimer's disease (AD). It's not specifically about ApoE 4/4, but does have useful information about thinking of AD progression as likely to involve a triad of key biomarkers (and maybe many more), which may signal important variations in what we call "Alzheimer's Disease".
The effect of ApoE ε 4 on clinical and structural MRI markers in prodromal Alzheimer’s disease
In 2018, the National Institute on Aging and Alzheimer’s Association (NIA-AA) proposed a new research framework focusing on diagnoses of AD with biomarkers for living persons (17). The scheme [which is labeled AT (N)] is based on grouping biomarkers into 3 categories: β amyloid deposition (A), pathologic tau (T), and neurodegeneration (N) (17). ...ApoE ε 4 (+) prodromal AD participants had lower levels of CSF Aβ 1-42, higher levels of t-Tau, more memory and global cognitive impairment, and faster decline of global cognition, compared to ApoE ε 4 (−) prodromal AD. ApoE ε 4 (+) prodromal AD participants had a thinner cortical thickness of bilateral entorhinal, smaller subcortical volume of the left amygdala, bilateral hippocampus, and left ventral diencephalon (DC) relative to ApoE ε 4 (−) prodromal AD. Furthermore, the cortical thickness average of bilateral entorhinal was highly correlated with memory and global cognition.
Another source of information on clinical trials, as well as information I only recently came to appreciate as important on pre-planning for those of us at risk. The Alzheimer's Association spends millions each year to support research on prevention and treatment of AD, and has a Trial Match of studies that include non-drug trials. You can read more here: Trial Match
The Alzheimer's Clinical Trial Consortium (ACTC) is a network of dozens of academic research centers collaborating to accelerate research, with funding from the National Institute on Aging (NIA/NIH). They have an online Alzheimer's Prevention Trial web study called for people who are 50 years or older. You can find information about it here: APT Webstudy Welcome
(Full disclosure: I am on the Research Participant Advisory Board for the ACTC, although I am not in any ACTC-sponsored clinical trial.)
To search for clinical trials (large and small) by your region, try the advanced search function on the NIH Clinical Trials website. Each trial has detailed information about its purpose, the criteria to join and contacts for study sites. Clinical Trials.gov
Apologies for a very long reply! I would love to hear what you think are the best textbooks or sources for people like me to develop some competency with statistics. I have read a great short book on reading medical studies, written by a British researcher based on his work with primary care docs seeking to be better consumers of research. I have the privilege to sit with researchers and biostatisticians once a year as a reviewer of grant proposals, They are always kind to this "consumer reviewer", and make me regret my decision to avoid statistics in favor of psychology in college!
If you have specific areas of dementia research you're looking into, let me know. We can both show that people with ApoE 4/4 continue to learn throughout our lives!