Midlife Vitamin D Levels Linked to Later Tau-PET Deposition

 I just exited midlife at age 70, so my stuff is already baked in. But then I have way more than 16 years to go, so maybe still time.

Midlife Vitamin D Levels Linked to Later Tau-PET Deposition

 Higher circulating vitamin D levels in early midlife are associated with lower tau deposition on brain positron emission tomography (PET) imaging in later midlife among adults without dementia, according to a study published in Neurology Open Access. In a prospective cohort study of adults without dementia from the Framingham Heart Study Generation 3 cohort, researchers evaluated whether serum 25-hydroxyvitamin D measured in early midlife is associated with later tau and amyloid burden on brain PET imaging.Serum 25-hydroxyvitamin D levels were assessed at examination cycle 1 between 2002 and 2005. Participants subsequently underwent amyloid PET and/or tau PET imaging between 2016 and 2019. [H]igher vitamin D levels in midlife may offer protection against pathologic tau deposition in the brain, while low vitamin D may represent a potentially modifiable risk factor for healthy middle-aged individuals seeking to reduce dementia risk. A total of 793 participants were included, of whom 53% were women, and the mean [SD] age was 39 [8] years. Of the participants, 424 underwent amyloid PET imaging, and 369 underwent tau PET. The mean (SD) interval between vitamin D measurement and PET imaging was 16.2 (2.4) years. Outcomes included global and composite tau-PET burden and amyloid-PET burden. In fully adjusted models, higher serum 25-hydroxyvitamin D levels were associated with lower global tau-PET burden (β=−0.022; 95% CI, −0.040 to −0.004;P=.010) and lower composite tau-PET burden (β=−0.023; 95% CI, −0.043 to −0.003;P=.016). In contrast, serum 25-hydroxyvitamin D levels were not associated with amyloid-PET burden (β=0.001; 95% CI, −0.024 to 0.024;P=.987). When analyzed using a clinical cutoff (<30 vs ≥30 ng/mL), serum 25-hydroxyvitamin D levels were not significantly associated with tau or amyloid PET outcomes in fully adjusted models. Baseline mean (SD) serum 25-hydroxyvitamin D level was 38 (15) ng/mL, with 34% of participants below 30 ng/mL. Sensitivity analyses excluding individuals taking vitamin D supplements yielded similar findings, with persistent associations between higher serum 25-hydroxyvitamin D and lower tau burden. Study limitations include a lack of repeated vitamin D measurements over time, and the long interval between vitamin D assessment and PET imaging, which may introduce exposure misclassification. This study suggests that higher vitamin D levels in midlife may offer protection against pathologic tau deposition in the brain, while low vitamin D may represent a potentially modifiable risk factor for healthy middle-aged individuals seeking to reduce dementia risk,” concluded the authors.

Adherence to the MIND diet and longitudinal brain structural changes over a decade: evidence from the Framingham heart study offspring cohort

 Ask your competent? doctor for EXACT DIET PROTOCOLS! None of this MIND diet guidelines; they have NO specifics! You need SPECIFICS!

 Adherence to the MIND diet and longitudinal brain structural changes over a decade: evidence from the Framingham heart study offspring cohort

1. http://orcid.org/0000-0003-2866-7811Hui Chen1,2,
2. Gulisiya Hailili1,
3. Lu-sha Tong3,
4. Leqi Fei1,
5. http://orcid.org/0000-0002-5024-2652Yaying Cao4,
6. Xin Xu1,
7. Xue Li1,5,
8. http://orcid.org/0000-0002-7392-9289Debora Melo van Lent6,7,8,
9. http://orcid.org/0000-0002-2389-8752Changzheng Yuan1,2

1. Correspondence to Professor Changzheng Yuan; chy478@zju.edu.cn

Abstract

Background The MIND diet was favourably linked to lower risk of neurodegenerative diseases. While previous cross-sectional studies implied its beneficial associations with brain imaging markers, its associations with long-term brain structural changes remained unclear.

Methods We included 1647 middle-aged and older individuals from the Framingham Heart Study Offspring cohort (FOS). MIND diet score was calculated from a validated FFQ, repeatedly administered at Exams 5, 6, and 7. Brain imaging markers were acquired between 1999 and 2019, with a median repetition (interquartile range, IQR) of 3 (2-3) times. We used linear mixed models to assess the associations of the MIND diet score and its components with longitudinal brain structural changes.

Results Over a median follow-up of 12.3 years (IQR 6.8–13.8 years), greater adherence to the MIND diet was associated with slower decline in total grey matter volume. Specifically, each three-unit increase in the MIND diet score was linked to a 0.279 cm³/year (95% CI 0.089 to 0.469) slower decline in total grey matter volume, corresponding to a 20.1% attenuation in age-related change that was equivalent to 2.5 years of reduced brain ageing during the 12.3-year follow-up. Additionally, higher MIND diet score was associated with slower increases in lateral ventricular volume (−0.071 cm³/year, 95% CI −0.125 to −0.017), notably in the left lateral ventricle (−0.041 cm³/year, 95% CI −0.070 to −0.013), reflecting approximately 8.0% and 8.8% attenuation of age-related changes, equivalent to roughly 1.0 year of delayed brain ageing during follow-up.

Conclusions In this prospective cohort study, greater adherence to the MIND diet was associated with slower brain structural atrophy, particularly regarding grey matter loss and ventricular enlargement. These findings support the potential of the MIND diet as a strategy to support brain health and delay structural brain ageing.

Data availability statement

Data may be obtained from a third party and are not publicly available. The Framingham Heart Study data are shared at the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC, https://biolincc.nhlbi.nih.gov/home/) on reasonable request.

https://doi.org/10.1136/jnnp-2025-336957

Physical Activity Over the Adult Life Course and Risk of Dementia in the Framingham Heart Study

 

3 years post stroke at a physical I had a resting heart rate of 54 at age 53, level of an athlete. My doctor asked what exercises I was doing, 'I've done no exercises for the past 3 years'. So now after 19 years of little exercise I'm no longer that athlete. Hopefully that physical activity in my midlife is enough to prevent dementia

Physical Activity Over the Adult Life Course and Risk of Dementia in the Framingham Heart Study

Francesca R. Marino, PhD¹ Chenglin Lyu,MS¹ Yuqing Li,MPH² Author Affiliations  

1 Department of Anatomy and Neurobiology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts 

2 Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts 

3 Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts 

4 Department of Neurology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts 

5 Slone Epidemiology Center, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts 

6 The Framingham Heart Study, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts 

7 Boston University Alzheimer’s Disease and Chronic Traumatic Encephalopathy Center, Department of Neurology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts 

Key Points

 Question When during the adult life course is physical activity most associated with risk of incident dementia? 

Findings

 In this cohort study of 1526 early adult–life, 1943 midlife, and 855 late-life participants in the Framingham Heart Study, individuals with the highest levels of physical activity at midlife and late life had 41% and 45% lower risk of all-cause dementia, respectively, compared with those with the lowest levels of physical activity, a statistically significant difference. Early adult–life physical activity was not associated with dementia risk. 

Meaning

  These findings suggest that timing efforts to promote physical activity during midlife or late life may be warranted to help delay or prevent dementia. 

Importance

 Being physically active is protective against dementia. Yet, it is unknown when during the adult life course physical activity is most associated with dementia risk. 

Objective

 To determine whether higher physical activity levels in early adult life, midlife, or late life are associated with lower risk of all-cause or Alzheimer disease (AD) dementia. 

Design, Setting, and Participants

 This prospective cohort study used data from the Framingham Heart Study Offspring cohort. The offspring of participants in the original Framingham Heart Study cohort who were dementia free and had physical activity measured at baseline (early adult life [1979-1983], midlife [1987-1991], or late life [1998-2001]) were followed up for a mean (SD) of 37.2 (7.1), 25.9 (8.5), or 14.5 (6.6) years for the development of incident all-cause or AD dementia until December 31, 2023. 

Exposure

 Physical activity was self-reported using the physical activity index, a composite score weighted by hours spent sleeping and in sedentary, slight, moderate, or heavy activities. Physical activity was divided into quintiles (Q). 

Main Outcome and Measure

 All-cause and AD dementia were classified by expert consensus based on established diagnostic criteria. 

Results

 This study included 1526 early adult–life (mean [SD] age, 36.7 [4.7] years; 821 [53.8%] female), 1943 midlife (mean [SD] age, 54.0 [5.8] years; 1010 [52.0%] female), and 885 late-life (mean [SD] age, 71.0 [4.5] years; 473 [53.4%] female) participants. There were 567 cases of incident all-cause dementia during follow-up. Higher levels of midlife and late-life physical activity were associated with lower risk of all-cause dementia. Midlife and late-life physical activity levels in Q4 or Q5 were associated with lower risk of all-cause dementia compared with Q1 (midlife Q4: HR, 0.60; 95% CI, 0.41-0.89; midlife Q5: HR, 0.59; 95% CI, 0.40-0.88; late-life Q4: HR, 0.64; 95% CI, 0.42-1.00; late-life Q5: HR, 0.55; 95% CI, 0.35-0.87). There were no associations between early adult–life physical activity and dementia risk. Findings were similar for incident AD (369 cases). 

Conclusions and Relevance

 In this cohort study of adults in the Framingham Heart Study Offspring cohort, higher levels of midlife and late-life physical activity were associated with similar reductions in risk of all-cause and AD dementia. These findings may inform future efforts to delay or prevent dementia through timing interventions during the most relevant stages of the adult life course.

AI Helps Predict Dementia Using Speech Patterns

 Can your competent? doctor test this on you and if found positive hand you the EXACT DEMENTIA PREVENTION PROTOCOLS they've known for decades are needed? NO? So you don't have a functioning stroke doctor!

Your chances of getting dementia.

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

The latest here:

AI Helps Predict Dementia Using Speech Patterns

Voice recordings may spot who's likely to progress to Alzheimer's dementia in 6 years

by Judy George, Deputy Managing Editor, MedPage Today June 26, 2024

Key Takeaways

• Voice recordings helped predict which patients with mild cognitive impairment developed Alzheimer's dementia in 6 years.
• The study leveraged AI methods for speech recognition and processed the resulting text using language models.
• Further prospective studies with larger populations are necessary to validate the findings.

Voice recordings helped predict which patients with mild cognitive impairment developed Alzheimer's dementia in 6 years.

Combined with basic demographic information, speech patterns recorded in neuropsychological exams achieved an accuracy of 78.5% and a sensitivity of 81.1% in predicting progression from mild cognitive impairment to dementia in a 6-year window, reported Ioannis Paschalidis, PhD, of Boston University, and colleagues in Alzheimer's & Dementia.

"However, the specificity of predicting whether an individual with mild cognitive impairment will progress to Alzheimer's disease within 6 years was moderate, at 75%," Paschalidis and co-authors wrote. "To reduce the costs associated with recruiting subjects for clinical trials, it is important to improve the specificity."

The study leveraged AI methods for speech recognition and processed the resulting text using language models. The researchers used the content of the interview -- words spoken and how they were structured -- not acoustic features like enunciation or talking speed.

The approach could be developed into a remote screening tool for predicting progression to Alzheimer's dementia, the researchers noted. "If you can predict what will happen, you have more of an opportunity and time window to intervene with drugs, and at least try to maintain the stability of the condition and prevent the transition to more severe forms of dementia," Paschalidis said in a statement.

In previous work, Paschalidis and colleagues reported that a model using natural language processing (NLP) discerned normal cognition from mild cognitive impairment and dementia based on voice recordings. Other researchers have found that speech patterns in phone conversations could spot people with early-to-moderate Alzheimer's dementia.

The current study evaluated neuropsychological test interviews of 166 Framingham Heart Study participants, including 90 people who had progressed from mild cognitive impairment to dementia within 6 years, and 76 people who had stable mild cognitive impairment in that period. The median age was 81, and nearly two-thirds of participants were women.

Neuropsychological test interviews were digitally recorded in the Framingham Heart Study. These hour-long interviews include cognitive tests like the Boston Naming Test, the Hooper Visual Organization Test, and the Wechsler Memory Scale.

"The neuropsychological test, triggered by patient history and in conjunction with a clinical examination, provides a comprehensive evaluation of cognitive function, including attention, memory, language, and visuospatial abilities," Paschalidis and co-authors observed.

"Researchers have explored computer-based approaches to predict the progression from mild cognitive impairment to dementia using neuropsychological tests, primarily relying on hand-crafted features and cognitive scores extracted from the neuropsychological test by clinicians," they pointed out. "However, these approaches have not yet achieved full automation, limiting their potential for more precise and efficient cognitive evaluations."

Paschalidis and colleagues used recorded neuropsychological test interviews to predict the likelihood of participants transitioning to Alzheimer's, training a model to spot connections among speech, demographics, diagnosis, and disease progression. The analysis used text automatically transcribed from the recordings.

The model's accuracy and sensitivity outperformed other measures at predicting progression to dementia in 6 years. Standard neuropsychological tests had an accuracy of 74.7% and sensitivity of 77.2%, for example. The Mini-Mental State Examination (MMSE) had an accuracy of predicting progression to dementia over 6 years of 62.9% and a sensitivity of 66.7%.

The study demonstrates the potential of automatic speech recognition and NLP techniques to develop a prediction tool to identify which patients with mild cognitive impairment are at risk of dementia, the researchers said.

"Our method achieved high accuracy and outperformed other non-invasive approaches," Paschalidis and co-authors wrote. "However, further prospective studies with larger populations are necessary to validate the generalizability of our models."

The definition of mild cognitive impairment needs to be standardized to better compare results, they noted. "With continued development and refinement, our approach may contribute to early intervention and selection in clinical trials for novel Alzheimer's disease treatments, ultimately improving patient outcomes," they wrote.

• Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

This research was funded in part by the National Science Foundation, National Institutes of Health, and Boston University Rajen Kilachand Fund for Integrated Life Science and Engineering.

Researchers reported relationships with Signant Health, Novo Nordisk, Biogen, Davos Alzheimer's Collaborative, NIH, American Heart Association, the Alzheimer's Drug Discovery Foundation, Alzheimer's Disease Data Initiative, Gates Ventures, Karen Toffler Charitable Trust, Johnson & Johnson, and AstraZeneca.

Primary Source

Alzheimer's & Dementia

Source Reference:Amini S, et al "Prediction of Alzheimer's disease progression within 6 years using speech: a novel approach leveraging language models" Alzheimers Dement 2024; DOI: 10.1002/alz.13886.

Can cocoa lower your heart disease risk?

Well shit I identified these from research years ago. I bet your stroke hospital still doesn't have a 24 hour coffee/cocoa station. Incompetence in action, I'd suggest firing the board of directors for not setting proper goals. 

Was this earlier research not good enough to write up protocols? Do they even know about this earlier research?

Flavanol-rich chocolate acutely improves arterial function and working memory performance counteracting the effects of sleep deprivation in healthy individuals June 2016

Cocoa Flavanols: Scientifically proven health benefits  Feb. 2016

 

Boosting Cocoa's Dementia-Fighting Benefits  Oct. 2015 

 

2 Cups of Hot Cocoa-a-Day Keeps the Neurologist Away  June 2015

 

 

Sweet dreams: eating chocolate prevents heart disease  June 2015

 

 Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) Study—a randomized controlled trial  Jan. 2015 

 

Blueberries, Avocados and Cocoa Beans May Keep Cardiologists at Bay  Jan. 2015

 

This Common Beverage Reversed Normal Age-Related Memory Loss in Three Months - Cocoa  Oct. 2014 

 

Cocoa Extract May Counter Specific Mechanisms of Alzheimer’s Disease  June 2014 

 

Could Hot Cocoa Improve Brainpower in Seniors?  Aug. 2013

 

Chocolate-loving countries produce more Nobel laureates  Oct. 2012

 

Eating small bar of chocolate cuts risks of stroke in men  Sept. 2012

 

Hot Cocoa May Boost Seniors' Brain Power  Aug. 2012

 

Dark Chocolate: Sweet Prevention for CV Events  June 2012

 The latest here:

 

Can cocoa lower your heart disease risk?

In a recent study published in Nutrients, researchers reviewed the effects of cocoa consumption on anthropometric measurements, blood pressure, and glycemic and lipid profiles to elucidate its impact on the risk of cardiovascular disease (CVD).

Study: Effects of Cocoa Consumption on Cardiometabolic Risk Markers: Meta-Analysis of Randomized Controlled Trials. Image Credit: iprachenko / Shutterstock.com

CVDs and the need for dietary interventions

Current estimates indicate that CVDs claim over 17.9 million lives each year, thus making these diseases the leading global cause of human mortality. In Brazil, over 397,000 individuals died due to CVDs in 2019, 43% of whom succumbed to coronary artery diseases.

The Framingham Heart Study is considered the pioneer of cardiometabolic research, as a significant portion of current cardiometabolic risk stratification has been based on its concepts. This study stratifies CVD risk based on age, sex, systolic and diastolic blood pressure, cholesterol, body mass index (BMI), and behaviors, including smoking and alcohol dependence. Notably, many of these factors have shown strong associations with diet, with a growing body of literature highlighting the role of healthy diets, such as the Mediterranean diet, in reducing CVD risk.

Cocoa is a fruit that is rich in polyphenols, the majority of which are flavonoids that have been shown to reduce the risk of both CVDs and artherosclerosis by reducing inflammation, improving endothelial function, and lowering blood pressure. More specifically, cocoa appears to activate nitric oxide (NO) and neutralize free radicals, thereby reducing oxidative stress and protecting cells from damage.  

To date, previous studies aimed at revealing the potential benefits of cocoa consumption on the Framingham risk score, a measure of cardiometabolic risk, have produced mixed results.

About the study

The present study involved a systematic review and meta-analysis of randomized control trials (RCTs) evaluating the associations between cocoa consumption and cardiometabolic risk markers.

RCTs that included individuals 18 years of age and older that used cocoa, its extracts, or dark chocolate, with a cocoa content of 70% or higher, were eligible for review inclusion. Studies conducted on pregnant or post-menopausal women, animal models, and those investigating the association between cardiometabolic risk and other comorbidities like cancer were excluded from the study.

Relevant publications were identified using six electronic scientific databases including MEDLINE, Web of Science, EMBASE, SciELO, LILACS, and Cochrane. The Rayyan reference manager was used for study data extraction and management.

Data on the reviewer, author, journal, publication year, country, methodology, cohort size, and participant details, including age, sex, amount of cocoa supplementation, follow-up period, and reported outcomes, were collected. The Cochrane risk of bias (RoB) tool was used to calculate bias risk between included studies.

The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to determine the strength of evidence of each included study against other studies in a paired-effects fashion. Higgins (I²) was used to test the degree of heterogeneity of included publications.

Study findings

Of the 3,807 studies initially identified in the database search, 31 met the study inclusion criteria and were included in the meta-analysis. Taken together, these studies included a cohort size of 1,110 cases and 876 controls.

Thirteen studies assessed the effects of cocoa supplementation on healthy participants, three on participants with metabolic syndrome, two on hypertension or pre-hypertension, seven with T2D, one on insulin resistance, and four on dyslipidemia or excess weight.

Cocoa consumption had no statistically significant effects on total body mass, waist circumference, or BMI. While abdominal circumference was reduced following cocoa supplementation interventions, these findings were borderline and were associated with high heterogeneity.

However, cocoa polyphenol consumption was found to reduce adverse lipid profiles, fasting blood glucose levels, and blood pressure, with the degree of reductions positively correlated with the dosage of cocoa intake. These findings may explain previously contrasting reports between studies, as cocoa elicited cardioprotective effects despite showing no improvements in some historic CVD risk markers.

Taken together, cocoa consumption, including cocoa supplements and dark chocolate, appears to impart protective effects on cardiometabolic risk markers and have a clinically significant impact on CVD risk reduction.

We suggest that the consumption of polyphenol-rich cocoa could be part of a strategy aimed at promoting cardiovascular health.”

Journal reference:

• Arisi, T. O. P., da Silva, D. S., Stein, E., et al. (2024). Effects of Cocoa Consumption on Cardiometabolic Risk Markers: Meta-Analysis of Randomized Controlled Trials. Nutrients 16(12):1919. doi:10.3390/nu16121919

Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria

How long before your competent? doctor puts together an EXACT DIET PROTOCOL that produces this beneficial gut microbiome? Or don't you have a functioning stroke doctor?

Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria

• Chenhao Li ¹¹
• Martin Stražar ¹¹
• Ahmed M.T. Mohamed
• 
  
• Stanley Y. Shaw
• Damian R. Plichta
• Ramnik J. Xavier ¹²
• Show all authors
• Show footnotes

Published:April 02, 2024DOI:https://doi.org/10.1016/j.cell.2024.03.014

Highlights

• •
  Multiomic profiling in FHS reveals microbes and metabolites associated with CVD
• •
  Oscillibacter species are associated with decreased blood and stool cholesterol
• •
  Homology searches and molecular networking predict cholesterol enzymes and products
• •
  Oscillibacter species encode for conserved cholesterol-metabolizing enzymes

Summary

Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multiomic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health.

Graphical abstract

• View Large Image
• Figure Viewer
• Download Hi-res image

BU researchers awarded $7.2 million to continue stroke surveillance research at the Framingham Heart Study

Ask your doctor what they have learned about stroke from the Framingham Heart Study. They know nothing; you don't have a functioning stroke doctor!

RUN AWAY!

BU researchers awarded $7.2 million to continue stroke surveillance research at the Framingham Heart Study 

Grant and Award Announcement

Boston University School of Medicine

(Boston)— Jose Rafael Romero, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, along with Hugo Javier Aparicio, MD, MPH, assistant professor of neurology, and Sudha Seshadri, MD, adjunct profess of neurology, have been awarded a five-year, $7.2 million grant from the National Institute of Neurological Disorders and Stroke. The funds will continue stroke surveillance research in Framingham Heart Study (FHS) cohorts and expand the research program to study post-stroke vascular cognitive impairment and dementia (PS-VCID), a critical public health challenge that contributes to nearly one-third of Alzheimer’s disease and related dementias.

 

The investigators seek to leverage FHS resources toward a better understanding of PS-VCID trends and determinants, study the causal relations of obesity and dyslipidemia with PS-VCID, and explore repurposing of available drug treatments. They will collaborate with the Reasons for Geographic and Racial Differences in Stroke (REGARDS) and Atherosclerosis Risk in Communities (ARIC) studies for development and validation of novel PS-VCID risk prediction tools, incorporating genetic, imaging, social and clinical data, for application in clinical practice and research.

 

Romero has been an FHS investigator since 2006. His research interests center on the study of cerebrovascular disease in subclinical stages, prevention of stroke, cognitive impairment and dementia and use of neuroimaging in the epidemiological study of cerebrovascular disease. Much of his current work centers on the epidemiological study of brain MRI markers of cerebral small vessel disease, their determinants and clinical consequences. As a board-certified neurologist and vascular neurologist, his clinical interests are in the prevention, diagnosis, treatment and rehabilitation of patients with stroke, with particular emphasis on under-represented racial and ethnic groups.

 

Aparicio has been a researcher at FHS since 2014. His research interests include the identification of lifestyle risk factors, biomarkers, neuroimaging markers and genetic influences associated with cerebrovascular diseases. He is particularly interested in the contributions of vascular risk factors to stroke, brain injury and aging, cognitive dysfunction and the development of Alzheimer’s disease, and the influence of sex, race, and ethnic disparities on these outcomes.

 

Seshadri has been a senior investigator at the Framingham Heart Study since 1998 and is founding director of the Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases at University of Texas Health San Antonio. She has led neurology research programs at FHS since 2005 and is a renowned expert in Alzheimer’s disease, dementia, stroke epidemiology and the genetics of stroke and vascular brain injury.

 

Launched in 1948, the goal of the FHS was to identify common factors or characteristics that contribute to cardiovascular disease. Over the years, the FHS has become a successful, multigenerational study that analyzes family patterns of cardiovascular and other diseases, while gathering more genetic information from the two generations that followed the original study participants. The FHS also has expanded to include diverse populations so that risk factors in these different groups can be understood. Boston University Chobanian & Avedisian School of Medicine has served as National Heart, Lung, and Blood Institute contractor and academic partner for the FHS study since 1971.

Midlife Omega-3 Levels Tied to Brain Structure, Cognition

What is your doctor doing to test for this and what protocol exists to make sure you are ingesting the right amounts? Since I'm going to live to 100, I'm in midlife at age 66 right now.

But all this risk for your doctor to explain:

Routine fish oil supplementation increases risk for incident AF

But this:

Fish oils do not prevent heart attack or strokes in people with diabetes

August 2018

And this:

Study: Fish Oil Supplements May Not Combat Stroke

March 2018 

And this:

Long-term consumption of sunflower and fish oils damages the liver

January 2018

And this:

Omega-3 Fatty Acid Supplementation and Warfarin: A Lethal Combination in Traumatic Brain Injury

 

The latest here:

Midlife Omega-3 Levels Tied to Brain Structure, Cognition

Larger hippocampal volume, better abstract reasoning for people in their 40s

by Judy George, Deputy Managing Editor, MedPage Today October 5, 2022

Omega-3 fatty acid concentrations in red blood cells were linked with brain structure and cognitive function in midlife, an exploratory cross-sectional study showed.

In about 2,200 people with an average age of 46, a higher omega-3 index was associated with a larger hippocampal volume and better abstract reasoning, according to Claudia Satizabal, PhD, of the University of Texas Health Science Center at San Antonio, and colleagues.

In addition, APOE4 carriers with a higher omega-3 index had a lower white matter hyperintensity burden, they reported in Neurology.

The omega-3 index combined docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations measured by gas chromatography.

The study is one of the first to identify relationships between omega-3 polyunsaturated fatty acids (PUFA), like DHA and EPA, and brain health in a younger population.

"The new contribution here is that, even at younger ages, if you have a diet that includes some omega-3 fatty acids, you are already protecting your brain for most of the indicators of brain aging that we see at middle age," Satizabal said in a statement.

Omega-3 fatty acids are obtained largely from dietary sources like cold-water, oily fish or omega-3 fortified foods, or through nutritional supplements. In the brain, DHA is incorporated into neuronal and glial cell membranes. Both DHA and EPA are metabolized into bioactive molecules involved in neurogenesis, neurotransmission, and inflammation resolution.

In older adults, observational studies have suggested that higher DHA and EPA intake may be protective for Alzheimer's disease. Omega-3 fatty acid levels also may protect older brains from environmental exposures like air pollution. Studies have linked pro-inflammatory diets, which are low in omega-3s, to brain volume and other markers of brain aging in older people.

"Despite the beneficial associations observed for brain outcomes in population-based and experimental studies, results from dietary intervention studies using omega-3 PUFA supplementation have been inconsistent," Satizabal and colleagues pointed out.

"These studies may be hampered in part by interventions that are deemed too late in the course of the disease, when individuals may have already experienced significant neuronal damage," they noted.

The researchers evaluated 2,183 predominantly middle-aged people in the Framingham Heart Study Third-Generation and Omni 2 cohorts who were dementia-free and stroke-free at baseline. Overall, 53% were women and 22% were APOE4 carriers.

Participants had brain MRI and cognitive function tests for episodic memory, processing speed, executive function, and abstract reasoning.

Higher levels of all omega-3 predictors -- EPA, DHA, and the omega-3 index -- were linked with larger hippocampal volumes when modeled continuously. Every standard deviation unit increase of log-transformed omega-3 index was related to 0.003 cm³ larger hippocampal volume relative to intracranial volume. Associations between higher omega-3 PUFA and larger hippocampal volumes remained significant after accounting for vascular risk factors.

All three omega-3 predictors were tied to better abstract reasoning test scores. Participants in the top three quartiles of EPA levels had better abstract reasoning performance than those in the bottom EPA quartile. Again, associations remained after adjusting for vascular risk factors.

Higher levels of all omega-3 predictors also were linked with reduced white matter hyperintensity volume in APOE4 carriers. Increasing EPA levels were tied to better performance in abstract reasoning tests in APOE4 carriers, but not in non-carriers.

The findings suggest that modest omega-3 consumption may be enough to preserve brain function, the researchers noted. "This is in line with the current American Heart Association dietary guidelines to consume at least two servings of fish per week to improve cardiovascular health," Satizabal said.

"These results need to be confirmed with additional research, but it's exciting that omega-3 levels could play a role in improving cognitive resilience, even in middle-aged people," she added.

Limitations include a largely white population in the study cohort and the cross-sectional design of the study, which provided only a snapshot in time, the researchers acknowledged.

• Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

The study was supported by the National Heart, Lung, and Blood Institute, National Institute on Aging, and National Institute of Neurological Disorders and Stroke.

Satizabal disclosed no relationships with industry. Co-authors disclosed relationships with Novartis Pharmaceuticals, OmegaQuant Analytics, Brainspan, Eisai, and Biogen.

Primary Source

Neurology

Source Reference: Satizabal CL, et al "Association of red blood cell omega-3 fatty acids with MRI markers and cognitive function in midlife: The Framingham Heart Study" Neurology 2022; DOI: 10.1212/WNL.0000000000201296.

Blood Profile at Age 35 Linked to Subsequent Alzheimer's Dementia

 I have zero clue what my readings were 30 years ago. It makes zero difference, your doctor is responsible to have EXACT Alzheimer's prevention protocols right now at your current age.

Blood Profile at Age 35 Linked to Subsequent Alzheimer's Dementia

Associations extend much earlier in life than previously thought

by Judy George, Senior Staff Writer, MedPage Today March 24, 2022

High-density lipoprotein (HDL) cholesterol and triglyceride levels in people as young as age 35 were linked with Alzheimer's dementia decades later in life, longitudinal data from the Framingham Heart Study showed.

Risk of Alzheimer's dementia fell by 15.4% during early adulthood (ages 35 to 50) and by 17.8% during middle adulthood (ages 51 to 60) for every 15 mg/dL increase in HDL cholesterol, reported Xiaoling Zhang, MD, PhD, of Boston University School of Medicine, and co-authors in Alzheimer's & Dementia.

A 15 mg/dL increase in blood glucose measured during middle adulthood was associated with a 14.5% increased Alzheimer's risk, they added. Triglyceride levels were associated with Alzheimer's only in the early adulthood group. Findings remained significant after adjusting for treatment.

"These findings show for the first time that cardiovascular risk factors, including HDL, which has not been consistently reported as a strong risk factor for Alzheimer's disease, contribute to future risk of Alzheimer's disease starting as early as age 35," Zhang said in a statement.

"While our findings confirm other studies that linked cholesterol and glucose levels measured in blood with future risk of Alzheimer's disease, we have shown for the first time that these associations extend much earlier in life than previously thought," added co-author Lindsay Farrer, PhD, also of Boston University.

The researchers looked at the influence of vascular risk factors on incident Alzheimer's dementia over time among Framingham Heart Study Offspring participants, a group that's been evaluated since 1971. Data on lipid fractions, glucose, blood pressure, BMI, and smoking were obtained prospectively from participants across nine quadrennial examinations.

Age-, sex-, and education-adjusted models were tested for each risk factor measured at each exam and within three adult age groups: early adults (ages 35 to 50, median 41), middle adults (ages 51 to 60, median 54), and late adults (ages 61 to 70, median 63.5).

A total of 271 participants (167 women, 104 men) diagnosed with Alzheimer's dementia were included in the analysis as cases. Of these, 225 people were without stroke, 24 people had Alzheimer's and stroke, and 24 people had mixed Alzheimer's and vascular dementia. People with a diagnosis of non-Alzheimer's dementia were excluded. Controls included 4,867 cognitively normal participants.

Mean follow-up periods for people in the early, middle, and late age groups were 35.2 years, 25.8 years, and 18.5 years, respectively. As participants grew older, they tended to have higher triglyceride and glucose levels, higher systolic and diastolic blood pressure, and lower HDL cholesterol levels. They also were more likely to be treated for diabetes, hypertension, and dyslipidemia.

Incident Alzheimer's dementia was negatively associated with HDL cholesterol for every 15 mg/dL increase in early adulthood (HR 0.85, 95% CI 0.72-0.99, P=0.041) and in middle adulthood (HR 0.82, 95% CI 0.70-0.96, P=0.014). This association remained significant with a similar effect size in the middle adulthood group when adjusted for dyslipidemia treatment (P=0.022).

Analyses also showed:

• Triglyceride levels were associated with Alzheimer's dementia only in the early adulthood group, before (HR 1.33, 95% CI 1.02-1.57, P=0.0013) and after (HR 1.30, 95% CI 1.10-1.54, P=0.0018) adjusting for dyslipidemia treatment
• Blood glucose in middle adulthood was associated with Alzheimer's dementia per 15 mg/dL increase, before (HR 1.15, 95% CI 1.06-1.23, P=0.00029) and after (HR 1.18, 95% CI 1.08-1.29, P=0.00036) adjusting for diabetes treatment
• Diastolic blood pressure in late adulthood was associated with Alzheimer's dementia per 10 mm increase, before (HR 1.14, 95% CI 1.01-1.29, P=0.041) and after (HR 1.14, 95% CI 1.00-1.29, P=0.044) adjusting for treatment
• Other vascular risk factors, including low-density lipoprotein (LDL) cholesterol, total cholesterol, BMI, smoking, and systolic blood pressure, were not associated with Alzheimer's dementia in any stage of adulthood (P>0.05)

Future development of Alzheimer's dementia was progressively higher and likely to occur earlier among people who had blood glucose in pre-diabetic (100 to 126 mg/dL) and diabetic (>126 mg/dL) ranges in early adulthood and middle adulthood.

"Intervention targeting cholesterol and glucose management starting in early adulthood can help maximize cognitive health in later life," Farrer suggested.

That idea is supported by previous studies of Framingham Offspring participants showing that elevated coronary heart disease risk and metabolic syndrome were associated with lower cognitive performance at age 55, Zhang and co-authors noted.

"However, our results do not distinguish whether the influences of these risk factors on the development of Alzheimer's disease may be particularly damaging during early adulthood and midlife or reflect longer accumulated risk exposure," they wrote.

The study had several limitations, the researchers acknowledged. All participants were white, and some early measurements of lipids and glucose were not under fasting conditions. In addition, the findings were based on analyses of one-time measurements.

• Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

This work was supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract, Boston University School of Medicine, the NIH, and the Alzheimer's Association.

Zhang had no disclosures.

Co-authors reported relationships with the Alzheimer's Drug Discovery Foundation, American Heart Association, Gates Ventures, Mass Mutual Insurance, Signant Health, Biogen, GlaxoSmithKline, Novo Nordisk, High Lantern, and the NIH.

Primary Source

Alzheimer's & Dementia

Source Reference: Zhang X, et al "Midlife lipid and glucose levels are associated with Alzheimer's disease" Alzheimer's Dement 2022; DOI: 10.1002/alz.12641.

 

 

Mid- to late- life body mass index and dementia risk: 38 years of follow-up of the Framingham Study

 You may have to double your dementia prevention protocols if this is you. I was never beyond a BMI of 25 until after my stroke at 50. And since my doctor did nothing that could get me back to all the activities I did to keep in shape I gained 30 pounds posts stroke.

Mid- to late- life body mass index and dementia risk: 38 years of follow-up of the Framingham Study

Li J, Joshi P, Fang T, et al.

American Journal of Epidemiology|April 14, 2021

Journal Summary

Given that growing evidence links body mass index (BMI) with poorer health, to explore this link, researchers analyzed 3,632 Framingham Offspring participants aged 20 to 60 years at their second health exam (1979-1982), with 190 cases of incident dementia detected by 2017. A higher risk of dementia that got lower after 70 years was observed in relation to each 1 kg/m ² increase in BMI at 40-49 years. A higher risk of dementia was noted in relation to obesity at 40-49 years. Overall, heterogeneity in the link between BMI and dementia risk was evident across the adult age range. The risk of dementia across an individual’s lifetime may be mediated by BMI monitoring at different age.

Journal Summary

Read the full article on American Journal of Epidemiology.

 

Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort

 Other analysis of this: found that low intake of anthocyanins in particular was associated with a four-fold increase in dementia risk. We don’t need to eat buckets of berries to tip the balance, however. High intake of flavonoids was equal to roughly 7.5 cups of blueberries or strawberries a month, or 8 apples or 19 cups of tea. 

Since I'm in Michigan, blueberries are abundant, I just freeze extra pints for winter use. I probably eat 1/3-1/2 cup each morning for breakfast.

Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort

Esra Shishtar, Gail T Rogers, Jeffrey B Blumberg, Rhoda Au, Paul F Jacques

The American Journal of Clinical Nutrition, Volume 112, Issue 2, August 2020, Pages 343–353, https://doi.org/10.1093/ajcn/nqaa079

Published:

22 April 2020

Article history

• PDF
• Split View
• Cite
• Permissions Icon Permissions
• Share

ABSTRACT

Background

Findings from existing prospective observational studies on the protective associations of flavonoid intake and the risk of Alzheimer disease and related dementias (ADRD) are inconsistent largely due to limitations of these studies.

Objectives

To examine the prospective relation between total and 6 classes of dietary flavonoid intake and risk of ADRD and Alzheimer disease (AD) while addressing limitations of earlier observational studies.

Methods

We used data from the Framingham Heart Study Offspring Cohort exams 5 through 9. Participants were ADRD-free with a valid FFQ at baseline. Flavonoid intakes were updated at each exam to represent the cumulative average intake across the 5 exams, and were expressed as percentile categories of intake (≤15th, >15th to 30th, >30th to 60th, >60th) to handle their nonlinear relation with ADRD and AD. Cox proportional hazards regression was used to estimate the HRs for the association between the flavonoid intakes and incidence of ADRD and AD.

Results

Over an average follow-up of 19.7 y in 2801 participants (mean baseline age = 59.1 y; 52% females), there were 193 ADRD events of which 158 were AD. After multivariate and dietary adjustments, individuals with the highest (>60th percentile) intakes of flavonols, anthocyanins, and flavonoid polymers had a lower risk of ADRD relative to individuals with the lowest intakes (≤15th percentile), with HRs (95% CI; P-trend) of 0.54 (0.32, 0.90; P = 0.003) for flavonols, 0.24 (0.15, 0.39; P < 0.001) for anthocyanins, and 0.58 (0.35, 0.94; P = 0.03) for flavonoid polymers. The same pattern of associations was seen with AD for flavonols and anthocyanins but not for flavonoid polymers.

Conclusions

Our findings imply that higher long-term dietary intakes of flavonoids are associated with lower risks of ADRD and AD in US adults.

 

Flavonoid intake and MRI markers of brain health in the Framingham Offspring cohort

Notice that this doesn't apply to us and our fucking failures of stroke associations

won't do the necessary studies to see how this might help stroke survivors. Don't do anything with this unless your doctor prescribes it. And since quartiles are not explained here your doctor needs to get the full clinical research so you know exactly how many bottles of red wine you should be consuming. My doctor told me I had a bunch of white matter hyperintensities but never showed me them on any scan, so I don't know the size or any intervention needed, because my doctor knew nothing.

The main dietary sources of flavonoids include tea, citrus fruit, citrus fruit juices, berries, red wine, apples, and legumes. Individual flavonoid intakes may vary considerably depending on whether tea, red wine, soy products, or fruit and vegetables are commonly consumed.

Flavonoid intake and MRI markers of brain health in the Framingham Offspring cohort

The Journal of Nutrition — Shishtar E, et al. | March 26, 2020

Researchers assessed MRI measures of brain health, including total brain tissue volume, white matter hyperintensities volume (WMHV), and hippocampal volume, in correlation with the intake of dietary flavonoid. Participants included members of the Framingham Heart Study Offspring Cohort who were free of stroke at exam 7 and had at least 1 valid food frequency questionnaire from exams 5, 6, or 7 (n = 2,086; mean age at exam 7, 60.6 y). Flavonoid intakes were grouped according to quartiles categories of consumption. In the highest quartile category of flavan-3-ols and flavonoid polymers intake vs in the lowest quartile category, the mean (95% CI) of the WMHV of participants was found to be significantly smaller after accounting for crucial demographic, lifestyle, and clinical factors. For flavan-3-ols and flavonoid polymers as well as for total flavonoids, inverse trend links with WMHV were also noted. The findings revealed a likely impact of higher flavonoid intakes on the risk of Alzheimer disease and related dementias (ADRD) in middle-aged and older adults, by causing a decrease in WMHV, a marker strongly related to ADRD. These findings contribute to the literature on flavonoids and ADRD.

Read the full article on The Journal of Nutrition