Predicting Alzheimers & Dementia (and minimizing risk)

[RapAdmin]

A recent Nature Medicine research report is sounding an alarm. The risk of developing dementia by the age of 95 is 42%. The finding that the risk of dementia increases with age is well described. What’s new and startling about this result is the number. It’s double prior estimates.

The investigator team, led by researchers at New York University and funded by the National Institutes of Health, reported even higher risk estimates for women, people who self-report Black racial identity, and carriers of a form of a gene associated with Alzheimer’s disease, one of the common causes of dementia.

Dementia cases expected to double by 2060; are you at risk?

United States Dementia Cases Estimated to Double by 2060

Dementia risk, higher than thought, requires a national strategy

[L_H]

I wonder what the effect size of having a wife who listens to you is?

[RapAdmin]

Researchers in China dug into the data and published their findings in January 2025 in The American Journal of Clinical Nutrition .5 Here’s what they found.

Data was pulled from the UK Biobank, a long-running database that houses anonymized health information and genetic data on half a million people living in the United Kingdom. For this study, more than 125,000 participants from the database met the inclusion criteria. One of these criteria included having completed a web-based 24-hour food diary at least twice during the 12-year follow-up period. This allowed researchers to determine how much dietary choline and choline-related compounds participants consumed on average. About 56% of the participants were women, and all participants had an average age of 56.

For dementia and Alzheimer’s, researchers found a U-shaped association with total choline intake. This means that people at the first and fourth quartiles experienced higher odds of developing dementia or Alzheimer’s. Those with the lowest odds of developing dementia and Alzheimer’s consumed, on average, about 354 mg/day and 338 mg/day of choline respectively. For context, that’s about as much choline as you would get from having two large eggs for breakfast in the morning.7

This Underrated Nutrient Could Help Lower Your Dementia Risk by 23%, New...

Source:

1. Zuk E, Nikrandt G, Chmurzynska A. Dietary choline intake in European and non-European populations: current status and future trends—a narrative review. Nutrition Journal. 2024. doi:10.1186/s12937-024-00970-0
2. National Institutes of Health. Choline.
3. Dymek A, Oleksy Ł, Stolarczyk A, Bartosiewicz A. Choline—an underappreciated component of a mother-to-be’s diet. Nutrients. 2024. doi:10.3390/nu16111767
4. Derbyshire E. Could we be overlooking a potential choline crisis in the United Kingdom? BMJ Nutrition, Prevention & Health. 2019. doi:10.1136/bmjnph-2019-000037
5. Niu Y, Yan H, Zhong J, et al. Association of dietary choline intake with incidence of dementia, Alzheimer disease, and mild cognitive impairment: a large population-based prospective cohort study. The American Journal of Clinical Nutrition. 2025. doi:10.1016/j.ajcnut.2024.11.001
6. Dementia Society of America. MCI.
7. U.S. Department of Agriculture. FoodData Central. Eggs, Grade A, Large, egg whole.
8. Gatarek P, Kaluzna-Czaplinska J. Trimethylamine N-oxide (TMAO) in human health. EXCLI Journal. 2021. doi: 10.17179/excli2020-3239
9. National Institutes of Health. Choline.

[DeStrider]

Galantamine is a drug used to prevent dementia that reduces the breakdown of choline in the brain. Which also gives you amazing dreams and could prevent sarcopenia when taken with Metformin.

[RapAdmin]

Mindfulness and social engagement are the two lifestyle factors that offer protection for those who carry the gene with the greatest risk for developing Alzheimer’s disease, according to a new study by researchers at the University of Miami Miller School of Medicine.

The researchers at the Comprehensive Center for Brain Health found that carriers of the APOE4 gene who practiced mindfulness and engaged in social activities had greater cognitive reserve than those who did not.

“The implications of this study are that it supports integrating APOE4 screening into personalized cognitive health strategies as specific lifestyle interventions that might offer particular benefits for individuals at risk due to having this allele,” said lead author Deirdre O’Shea, Ph.D., assistant professor and clinical neuropsychologist at the Miller School.

Dr. O’Shea’s research focuses on understanding risk and resilience factors in cognitive dementia, especially by looking at cognitive reserve.

Worried About Alzheimer's? Meditate and Mingle, Study Says - InventUM

[RapAdmin]

Source: x.com

[RapAdmin]

Perhaps relevant for humans too…

Source: x.com

全文：Enhancing cognitive functions in aged dogs and cats: a systematic review of enriched diets and nutraceuticals

[RapAdmin]

Summary: The microbial ecosystems in our mouths may impact cognitive function as we age, with pathogenic bacteria linked to cognitive decline. Researchers found that beneficial bacteria, such as Neisseria, are associated with improved memory and attention, while harmful bacteria like Porphyromonas correlate with mild cognitive impairment.

These findings suggest that diet, particularly nitrate-rich foods, could promote beneficial bacteria and support brain health. Further research may reveal how oral health interventions could help delay cognitive decline and reduce the risk of dementia or Alzheimer’s disease.

Key Facts:

• Microbial Connection: Beneficial oral bacteria, like Neisseria, support cognitive functions, while harmful bacteria, such as Porphyromonas, predict cognitive decline.
• Dietary Influence: A nitrate-rich diet fosters beneficial oral bacteria linked to better cognitive outcomes.
• APOE4 Link: Specific harmful bacteria (Prevotella intermedia) are associated with the APOE4 allele, a known risk factor for Alzheimer’s.

Oral Microbiome May Influence Cognitive Decline and Brain Health -...

Open Access Paper:

Oral microbiome and nitric oxide biomarkers in older people with mild cognitive impairment and APOE4 genotype

Apolipoprotein E4 (APOE4 ) genotype and nitric oxide (NO) deficiency are risk factors for age-associated cognitive decline. The oral microbiome plays a critical role in maintaining NO bioavailability during aging. The aim of this study was to assess interactions between the oral microbiome, NO biomarkers, and cognitive function in 60 participants with mild cognitive impairment (MCI) and 60 healthy controls using weighted gene co-occurrence network analysis and to compare the oral microbiomes between APOE4 carriers and noncarriers in a subgroup of 35 MCI participants. Within the MCI group, a high relative abundance of Neisseria was associated with better indices of cognition relating to executive function (Switching Stroop, rs = 0.33, P = 0.03) and visual attention (Trail Making, rs = −0.30, P = 0.05), and in the healthy group, Neisseria correlated with working memory (Digit Span, rs = 0.26, P = 0.04). High abundances of Haemophilus (rs = 0.38, P = 0.01) and Haemophilus parainfluenzae (rs = 0.32, P = 0.03), that co-occurred with Neisseria correlated with better scores on executive function (Switching Stroop) in the MCI group. There were no differences in oral nitrate (P = 0.48) or nitrite concentrations (P = 0.84) between the MCI and healthy groups. Linear discriminant analysis Effect Size identified Porphyromonas as a predictor for MCI and Prevotella intermedia as a predictor of APOE4 -carrier status. The principal findings of this study were that a greater prevalence of oral P. intermedia is linked to elevated genetic risk for dementia (APOE4 genotype) in individuals with MCI prior to dementia diagnosis and that interventions that promote the oral Neisseria–Haemophilus and suppress Prevotella -dominated modules have potential for delaying cognitive decline.

https://academic.oup.com/pnasnexus/article/4/1/pgae543/7960038?login=false

[RapAdmin]

Higher levels of amyloid, tau

Researchers followed 128 people with an average age of 70 from the neurology unit of the China-Japan Friendship Hospital in Beijing. Half had Alzheimer’s, and about one-third had mild cognitive impairment, a frequent precursor to Alzheimer’s. The rest had normal cognition.

The participants in the study slept overnight in the clinic, so researchers could measure their brainwave activity, eye movement, heartrate and breathing. Fitness trackers can capture some of this information, but it is less precise.

The researchers divided the participants into early and delayed REM sleep. On average, the early group reached REM less than 98 minutes after falling asleep, while the late group reached it more than 193 minutes after falling asleep.

Those with Alzheimer’s were more likely to have delayed REM sleep, and they also tended to have higher levels of the two toxic proteins, amyloid and tau, found in people with the condition.

Those with delayed REM sleep had 16% more amyloid and 29% more tau than those with early REM sleep. They also had 39% less of a healthy protein called brain derived neurotrophic factor (BDNF), which drops in Alzheimer’s.

Delayed REM Sleep Could Be an Early Sign of Alzheimer’s

[CronosTempi]

Important result! Maybe finally all those gizmos that claim to detect what phase of sleep you are in can earn their keep, insofar as predicting the approach of AD, so you can take emergency measures desperately trying to avoid dementia, as excess tau is bad regardless of AD.

[L_H]

Interesting speculation as to why high choline intake might correlate with dementia incidence:

“Wondering why a high intake of choline seemed to increase the odds of dementia and Alzheimer’s almost as much as the lowest intake did? Researchers explain that when choline intake exceeds the intestine’s capacity to absorb it all, the unabsorbed choline is changed into a compound called trimethylamine (TMA), which is further changed by the liver into trimethylamine N-oxide (TMAO). These substances are linked to heart disease, stroke and, yes, Alzheimer’s disease.8 Another explanation, according to the researchers, is that some common foods rich in choline are also high in saturated fat, and there has been a link between high saturated fat intake and dementia in previous studies.”

[L_H]

an argument for phosphatidylcholine…?

"Participants’ plasma TMAO levels increased significantly in all 3 intervention arms containing choline bitartrate (all P < .0001), but daily ingestion of 4 large eggs (P = .28) or phosphatidylcholine supplements (P = .27) failed to increase plasma TMAO levels.

Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in...

[Josh]

Taking tmg reduces need for choline as well. I take 1g a day and it lowered my homocysteine without raising my blood tmao levels at all, quite low, but my dietary choline intake is probably too low since tmg lowered my homocysteine so much…
Maybe half gram tmg and supplementing choline would be even better for me? (Hit all pathways and still not raise tmao)

Wikipedia says:
Nutritionally, betaine is not needed when sufficient dietary choline is present for synthesis.[18] When insufficient betaine is available, elevated homocysteine levels and decreased SAM levels in blood occur. Supplementation of betaine in this situation would resolve these blood marker issues, but not compensate for other functions of choline

[RapAdmin]

Cannabis use causes memory problems, and they may be permanent

Largest Study Ever Done on Cannabis and Brain Function Finds Impact on...

Cannabis use causes memory problems, and they may be permanent

[amuser]

Narrative violation -

‘…propensity of ind(ividual)s with certain traits to pursue more education.’

https://x.com/AndersFjell/status/1884887398707826741

Reevaluating the Role of Education in Cognitive Decline and Brain Aging:...

[adssx]

@amuser

Narrative violation

How is this a narrative violation? For me this has always been the definition of the cognitive reserve. (Also smart people find ways to cope with mild cognitive impairment, such as note taking, and can delay the dementia diagnosis in practice, I saw that with my grandfather.)

[RapAdmin]

Fluctuating Cholesterol Tied to Higher Dementia Risk

Unexplained lipid changes in older adults may foretell cognitive decline, study suggests

Year-to-year fluctuations in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were tied to higher risks of cognitive decline and dementia, a study of nearly 10,000 older adults showed.

Participants with the highest variability in total cholesterol had a 60% higher risk of incident dementia (HR 1.60, 95% CI 1.23-2.08) and a 23% higher risk of cognitive decline without dementia (HR 1.23, 95% CI 1.08-1.41), reported Zhen Zhou, PhD, of Monash University in Melbourne, Australia, and co-authors in Neurologyopens in a new tab or window.

https://www.medpagetoday.com/neurology/dementia/114002

[amuser]

I think the study has implications for the validity of the oft-made assertion that ‘mental exercise’ into old age will stave off cognitive decline.

[adssx]

No the study is about early life education (did you go to high school, undergrad, master, PhD, etc.) It is unrelated to late life cognitive exercise.

[RapAdmin]

Open Access Paper:

Bioaccumulation of microplastics in decedent human brains

Rising global concentrations of environmental microplastics and nanoplastics (MNPs) drive concerns for human exposure and health outcomes. Complementary methods for the robust detection of tissue MNPs, including pyrolysis gas chromatography–mass spectrometry, attenuated total reflectance–Fourier transform infrared spectroscopy and electron microscopy with energy-dispersive spectroscopy, confirm the presence of MNPs in human kidney, liver and brain. MNPs in these organs primarily consist of polyethylene, with lesser but significant concentrations of other polymers. Brain tissues harbor higher proportions of polyethylene compared to the composition of the plastics in liver or kidney, and electron microscopy verified the nature of the isolated brain MNPs, which present largely as nanoscale shard-like fragments. Plastic concentrations in these decedent tissues were not influenced by age, sex, race/ethnicity or cause of death; the time of death (2016 versus 2024) was a significant factor, with increasing MNP concentrations over time in both liver and brain samples (P = 0.01). Finally, even greater accumulation of MNPs was observed in a cohort of decedent brains with documented dementia diagnosis, with notable deposition in cerebrovascular walls and immune cells. These results highlight a critical need to better understand the routes of exposure, uptake and clearance pathways and potential health consequences of plastics in human tissues, particularly in the brain.

https://www.nature.com/articles/s41591-024-03453-1

Eric Topol’s Analysis:

This issue of Ground Truths sums ups a worrisome new report on brain accumulation of microplastics, increasing over time assessed, with much higher levels in people with dementia, including Alzheimer’s disease. It comes on top of a new study in the experimental model showing microplastics impair brain blood vessel flow and induce blood clots. While these reports do not establish cause-and-effect, they add to a growing body of deeply concerning evidence on the toxic effects of these pervasive substances for our health.

The Microplastic Concerns Elevate—To the Brain

Plastic shards permeate human brains