Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission

Your competent? doctor distilled these 57 pages from 2024 into understandable protocols, right! Oh no, NOTHING HAPPENED, LIKE USUAL!

Do you prefer your doctor and hospital incompetence NOT KNOWING? OR NOT DOING?

The reason you need dementia prevention: 

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. 

 Dementia prevention, intervention, and care: 2024 report of
the Lancet standing Commission

 I liked this diagram on page 22.

Figure 9: Population attributable fraction of potentially modifiable risk factors for dementia

You can slow cognitive decline as you age, large study finds. Here’s how

 Have your competent? doctors get the EXACT TRAINING PROTOCOLS! Oh, your doctor won't do that? FIRE THEM!

You can slow cognitive decline as you age, large study finds. Here’s how

             At 62, Phyllis Jones felt trapped in darkness. She was traumatized by her mother’s recent death, ongoing pandemic stress and an increasingly toxic work environment. A sudden panic attack led to a medical leave.

Her depression worsened until the day her 33-year-old son sadly told her, “Mom, I didn’t think I would have to be your caregiver at this stage in your life.”

“For me, that was the wake-up call,” Jones, now 66, told CNN. “That’s when I found the POINTER study and my life changed. What I accomplished during the study was phenomenal — I’m a new person.”

The Protect Brain Health Through Lifestyle Intervention to Reduce Risk, or US POINTER study, is the largest randomized clinical trial in the United States designed to examine whether lifestyle interventions can protect cognitive function in older adults.

“These are cognitively healthy people between the ages of 60 and 79 who, to be in the study, had to be completely sedentary and at risk for dementia due to health issues such as prediabetes and borderline high blood pressure,” said principal investigator Laura Baker, a professor of gerontology, geriatrics and internal medicine at Wake Forest University School of Medicine in Winston-Salem, North Carolina.

Approximately one-half of the 2,111 study participants attended 38 structured team meetings over two years in local neighborhoods near Chicago, Houston, Winston-Salem, Sacramento, California, and Providence, Rhode Island. During each session, a trained facilitator provided guidance on how to exercise and eat for the brain, and explained the importance of socialization, the use of brain-training games, and the basics of brain health. The team leader also held the group accountable for logging blood pressure and other vitals. Physical and cognitive exams by a physician occurred every six months.

At six team meetings, the other half of the study’s participants learned about brain health and were encouraged to select lifestyle changes that best suited their schedules. This group was self-guided, with no goal-directed coaching. These participants also received physical and cognitive exams every six months.

The two-year results of the $50 million study, funded by the Alzheimer’s Association, were simultaneously presented Monday at the 2025 Alzheimer’s Association International Conference in Toronto and published in the journal JAMA.

“We found people in the structured program appeared to delay normal cognitive aging by one to nearly two years over and above the self-guided group — people who did not receive the same degree of support,” Baker said. “However, the self-guided group improved their cognitive scores over time as well.”

Exercise, diet and socializing are key

Exercise was the first challenge. Like the other groups across the country, Jones and her Aurora, Illinois, team received YMCA memberships and lessons on how to use the gym equipment. Jones was told to use aerobic exercise to raise her heart rate for 30 minutes a day while adding strength training and stretching several times a week.

At first, it wasn’t easy.

The study participants wore fitness trackers that monitored their activity, Jones said. “After that first 10 minutes, I was sweating and exhausted,” she said. “But we went slow, adding 10 minutes at a time, and we kept each other honest. Now I just love to work out.”

Four weeks later, teams were given a new challenge — beginning the Mediterranean-DASH Intervention for Neurodegenerative Delay, or MIND diet. The diet combines the best of the Mediterranean diet with the salt restrictions of the DASH diet, which stands for Dietary Approaches to Stop Hypertension.

“They gave us a refrigerator chart with foods to limit and foods to enjoy,” Jones said. “We had to eat berries and vegetables most days, including green leafy veggies, which was a separate item. We had to have 2 tablespoons of extra-virgin olive oil once every day.”

Foods to limit included fried food, processed meat, dairy, cheese and butter. Restrictions were also in place for sugary sweets. “But we could have dessert four times a week,” Jones added. “That’s awesome because you’re not completely depriving yourself.”

Another pillar of the program was requiring study participants to familiarize themselves with their vital signs, Wake Forest’s Baker said. “If at any point we asked them, ‘What’s your average blood pressure?’ they should be able to tell us,” she said. “We encouraged people to monitor their blood sugar as well.”

Later came brain training, via memberships to a popular, Web-based cognitive training app. While some scientists say the benefits of such online brain programs have yet to be proven, Jones said she enjoyed the mental stimulation.

Becoming better at socializing was another key part of the program. The researchers tasked teams with assignments, such as speaking to strangers or going out with friends.(My socialization is live jazz at bars and trivia, I'm sure no-nos since alcohol is involved))

“I found my best friend, Patty Kelly, on my team,” Jones said. “At 81, she’s older than me, but we do all sorts of things together — in fact, she’s coming with me to Toronto when I speak at the Alzheimer’s conference.

“Isolation is horrible for your brain,” she added. “But once you get to a point where you are moving and eating healthy, your energy level changes, and I think you automatically become more social.”

As the study progressed, the researchers reduced check-ins to twice a month, then once a month, Baker said.

“We were trying to get people to say, ‘I am now a healthy person,’ because if you believe that, you start making decisions which agree with the new perception of yourself,” she said.

“So in the beginning, we were holding their hands, but by the end, they were flying on their own,” Baker added. “And that was the whole idea — get them to fly on their own.”

‘Brain health is a long game’

Because researchers tracked each team closely, the study has a wealth of data that has yet to be mined.

“On any given day, I could go into our web-based data system and see how much exercise someone’s doing, whether they’ve logged into brain training that day, what’s their latest MIND diet score, and whether they’d attended the last team meeting,” Baker said.

“We also have sleep data, blood biomarkers, brain scans and other variables, which will provide more clarity on which parts of the intervention were most successful.”

Digging deeper into the data is important, Baker says, because the study has limitations, such as the potential for a well-known phenomenon called the practice effect.

“Even though we use different stimuli within tests, the act of taking a test over and over makes you more familiar with the situation — you know where the clinic is, where to park, you’re more comfortable with your examiner,” she said.

“You’re not really smarter, you’re just more relaxed and comfortable, so therefore you do better on the test,” Baker said. “So while we’re thrilled both groups in US POINTER appear to have improved their global cognition (thinking, learning and problem-solving), we have to be cautious in our interpretations.”

It’s important to note the POINTER study was not designed to provide the more immersive lifestyle interventions needed for people with early stages of Alzheimer’s, said Dr. Dean Ornish, a professor of medicine at the University of California, San Francisco.

Ornish published a June 2024 clinical trial that found a strict vegan diet, daily exercise, structured stress reduction and frequent socialization could often stop the decline or even improve cognition in those already experiencing from early-stage Alzheimer’s disease, not just for those at risk for it.

“The US POINTER randomized clinical trial is a landmark study showing that moderate lifestyle changes in diet, exercise, socialization and more can improve cognition in those at risk for dementia,” said Ornish, creator of the Ornish diet and lifestyle medicine program and coauthor of “Undo It!: How Simple Lifestyle Changes Can Reverse Most Chronic Diseases.”

“It complements our randomized clinical trial findings which found that more intensive multiple lifestyle changes often improve cognition in those already diagnosed with early-stage Alzheimer’s disease,” Ornish said. “But the US POINTER study showed that more moderate lifestyle changes may be sufficient to help prevent it.”

In reality, two years isn’t sufficient to track brain changes over time, said study coauthor Maria Carillo, chief science officer of the Alzheimer’s Association.

“We really want to make recommendations that are evidence based,” Carillo told CNN. “That’s why we have invested another $40 million in a four-year follow-up, and I believe over 80% of the original participants have joined.

“Brain health is a long game,” she added. “It’s hard to track, but over time, change can be meaningful.”     

Copper Intake Linked to Cognitive Health in Older Adults, suggests study

 One line in there is important; 'beneficial connections were more strong in people with a history of stroke'. Ask your doctor for EXACT AMOUNTS TO GET! NO answer; you DON'T have a functioning stroke doctor, do you?

But your incompetent? doctor did nothing with this; correct? Almost 2 full years of incompetence!

Brain copper may protect from cognitive decline and Alzheimer’s disease pathology: a community-based study October 2022 

The latest here:

Copper Intake Linked to Cognitive Health in Older Adults, suggests study

The yin and yang of safety and risk: a content analysis and critical narrative synthesis exploring the conceptualisation of risk in the stroke rehabilitation literature

My risk taking started my first day release from the hospital; went to watch a whitewater slalom race with a quarter mile rough path to get to the banks. Nurses found out about it and I got a stern visit from one of my doctors highly recommending against it. I totally ignored her since she obviously knew nothing about my risk taking. I was damn good at OC1 and OC2 slaloms and wasn't going to miss it.

The trophies are from the Buttercup series of whitewater slalom races(6 races in Wisconsin and Minnesota).

Left is 1rst place OC1(Open Canoe 1 person) 2004

Middle is 2nd place OC1(Open Canoe 1 person) 2003

Right is 3rd place OC1(Open Canoe 1 person) 2005, stroke was in May 2006

Missing are the two first place finishes in OC2(Open Canoe 2 person) in consecutive years with different paddling partners, they have the trophies.

One of my main reasons for my excellent balance is this: Don't follow me, I'm not medically trained, is your doctor?

bar stool rehab (3 posts to January 2014)

 The yin and yang of safety and risk: a content analysis and critical narrative synthesis exploring the conceptualisation of risk in the stroke rehabilitation literature

Sharon Jackson

,

Sara Demain

,

Francine O’Malley

 &

Dorit Kunkel

Received 04 Oct 2024, Accepted 11 Jul 2025, Published online: 25 Jul 2025

• Cite this article
 
• https://doi.org/10.1080/13698575.2025.2535973
 
• CrossMark

(open in a new window)

Abstract

Many people feel unprepared for life following discharge from stroke services. Rehabilitation occurs within a harm-reduction framework, but evidence suggests risk-taking is crucial for recovery. The aims of this review study were to explore how risk is conceptualised in the stroke rehabilitation literature and to develop a critical narrative synthesis of articles exploring and challenging dominant conceptualisations of risk, in the context of post-stroke identity and engagement in valued activities. We undertook a literature search (including Embase, PubMed, CINHAL and PsycINFO), including qualitative, quantitative and mixed-methods studies in post-stroke adults > 18 years. Phase 1 involved a content analysis, with 1420 articles screened and 246 included. Most (n = 233) were described by the theme ‘Safety first’, divided into sub-themes: i) Physical safety; ii) Societal and organisational protection; and iii) Cognitive, affective and communication risks. Remaining articles were described by Theme 2: ‘Taking risks as necessary and subjective’. Critical narrative synthesis in Phase 2 included fifteen articles, demonstrating the imposition of ‘rules’ for safety, despite risk-taking being important. The predominant narrative prioritised safety and harm-reduction during stroke rehabilitation, overlooking unintended consequences for post-stroke identity and engagement in valued activities. The voice of people post-stroke was largely absent(So, not listening to the experts in the field.) in decision-making around risk prioritisation and management, which often failed to acknowledge the inherent uncertainties and sociocultural factors influencing beliefs and behaviours in relation to risk. Further qualitative research is needed to understand the experiences of people post-stroke and to inform service co-design and shared decision-making in relation to risk in stroke rehabilitation.

Retina is a Marker for Cerebrovascular Heath

Whomever wrote this didn't know that stroke has been called neurological disease by the WHO since 2006 not cerebrovascular, once again proving the stroke medical world doesn't keep up to date in their field!

Retina is a Marker for Cerebrovascular Heath

ClinicalTrials.gov ID NCT04753970

Sponsor:Mayo Clinic 

Information Provided by:Michelle P Lin, MD, MPH 

Study Start (Actual)2021-02-09 

Primary Completion (Estimated) 2026-06 

Study Completion (Estimated)2026-06 

Enrollment (Estimated)100 

Study Type: Interventional 

Last Update Posted2025-07-23 Study Overview

Brief Summary

Cerebral small vessel disease (SVD), present in 80-94% of adults over age 65 years, increases the risk of stroke by 2-fold, and dementia by 2.3-fold. There is currently no treatment to slow SVD progression. This study aims to test whether impaired cerebral and retinal vasoreactivity may serve as biomarker for SVD progression, and to evaluate the safety and efficacy of cilostazol (antiplatelet agent with vasodilatory and anti-inflammatory properties) for the treatment of SVD.

ClinicalTrials.gov

Distal Ischemic Stroke Treatment With Adjustable Low-profile Stentriever

 From the start you can see that the stroke medical world has the wrong goals for research! Restoring blood flow IS NOT THE SURVIVORS PRIMARY GOAL! 100% RECOVERY IS!

As you can see the stroke medical world has NO understanding of how to run the business of stroke recovery!

You're not even trying for 100% recovery! You're fired!

“What's measured, improves.” So said management legend and author Peter F. Drucker 

Distal Ischemic Stroke Treatment With Adjustable Low-profile Stentriever

ClinicalTrials.gov ID NCT05152524

 Sponsor Rapid Medical 

Information Provided by 

Study Start (Actual)2022-03-25 

Primary Completion (Estimated) 2025-11 

Study Completion (Estimated)2026-01 

Enrollment (Estimated)168

Study TypeInterventional

Last Update Posted2025-07-23

Study Overview

Brief Summary

The objective of the DISTALS Study is to evaluate the safety and effectiveness of the Tigertriever 13 Revascularization Device in restoring blood flow in the neurovasculature by removing thrombus in patients presenting within 24 hours of onset with an ischemic stroke with disabling neurological deficits due to a primary distal vessel occlusion (DVO), as compared to medical management.ClinicalTrials.gov

Your Gut May Be the Key to Chronic Fatigue, Long COVID

Will your competent? doctor be studying this closely to see if stroke fatigue can be solved via this intervention? Oh NO, you DON'T have a functioning stroke doctor, do you?

At least half of all stroke survivors experience fatigue Known since March 2017

Or is it 70%? Known since March 2015

Or is it 40%? Known since September 2017

Your Gut May Be the Key to Chronic Fatigue, Long COVID

Q: A: The study revealed that ME/CFS disrupts key interactions between the gut microbiome, immune system, and metabolism, identifying biological markers that distinguish patients from healthy individuals with up to 90% accuracy.Q: >How does the AI platform, BioMapAI, help?A:

 BioMapAI integrates thousands of data points—including microbiome profiles, blood tests, immune markers, and symptoms—to identify patterns and disruptions unique to ME/CFS, making precision medicine approaches more feasible.

Q: Why are these findings important for patients?
A: The research not only strengthens the biological legitimacy of ME/CFS but also offers personalized insight into symptom origins, potentially guiding future dietary, lifestyle, and therapeutic interventions—especially for long COVID and related conditions.

Summary: A groundbreaking study using AI has revealed how ME/CFS disrupts critical connections between the immune system, gut microbiome, and metabolism. The new platform, BioMapAI, achieved 90% accuracy in identifying ME/CFS patients based on stool, blood, and symptom data—offering long-overdue validation for millions living with this debilitating illness.

Researchers found that patients had distinct biological signatures, including lower levels of beneficial fatty acids, disrupted immune cell activity, and metabolic imbalances. These findings could guide personalized treatments and provide a scientific foundation for future therapies, especially for long COVID sufferers with overlapping symptoms.

Key Facts:

• AI Breakthrough: BioMapAI distinguished ME/CFS patients with 90% accuracy using immune, microbiome, and metabolic data.
• Biological Signatures: Patients showed disrupted tryptophan metabolism, inflammatory immune cells, and reduced butyrate levels.
• Precision Medicine Potential: Findings may lead to targeted interventions for ME/CFS and long COVID.

Source: Jackson Laboratory

Millions suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a debilitating condition often overlooked due to the lack of diagnostic tools, may be closer to personalized care, according to new research that shows how the disease disrupts interactions between the microbiome, immune system, and metabolism.

The findings—potentially relevant to long COVID due to its similarity with ME/CFS—come from data on 249 individuals analyzed using a new artificial intelligence (AI) platform that identifies disease biomarkers from stool, blood, and other routine lab tests.

The researchers intend to share their dataset broadly with BioMapAI, which supports analyses across diverse symptoms and diseases, effectively integrating multi-omics data that are difficult to replicate in animal models. Credit: Neuroscience News“Our study achieved 90% accuracy in distinguishing individuals with chronic fatigue syndrome, which is significant because doctors currently lack reliable biomarkers for diagnosis,” said study author Dr. Derya Unutmaz, Professor in immunology at The Jackson Laboratory (JAX).

“Some physicians doubt it as a real disease due to the absence of clear laboratory markers, sometimes attributing it to psychological factors.”

The research was led by  Dr. Julia Oh, formerly at JAX and now a microbiologist and professor at Duke University, in collaboration with ME/CFS clinicians Lucinda Bateman and Suzanne Vernon of the Bateman Horne Center, and Unutmaz, who directs the JAX ME/CFS Collaborative Research Center. Details appear today in Nature Medicine.

Mapping the Invisible

Chronic fatigue syndrome is characterized by severe symptoms that significantly impair physical and mental activities, including persistent fatigue, sleep abnormalities, dizziness, and chronic pain.

Experts often compare ME/CFS to long COVID, as both conditions frequently follow viral infections, such as Epstein-Barr virus. In the United States, ME/CFS affects between 836,000 and 3.3 million individuals— many undiagnosed—and costs the economy $18 to $51 billion annually due to healthcare expenditures and lost productivity, according to the Centers for Disease Control and Prevention.

Prior studies have noted immune disruptions in ME/CFS, Unutmaz said. This new research builds upon those findings by investigating how the gut microbiome, its metabolites, and immune responses interact.

The team linked these connections to 12 classes of patient-reported symptoms, which were aggregated from hundreds of datapoints generated by patient health and lifestyle surveys.

These include sleep disturbances, headaches, fatigue, dizziness, and other symptoms the researchers  mapped in their entirety from microbiome changes to metabolites, immune responses, and clinical symptoms.

“We integrated clinical symptoms with cutting-edge omics technologies to identify new biomarkers of ME/CFS,” Oh said. “Linking symptoms at this level is crucial, because ME/CFS is highly variable. Patients experience a wide range of symptoms that differ in severity and duration, and current methods can’t fully capture that complexity.” 

To conduct the study, the researchers analyzed comprehensive data collected from the Bateman Horne Center, a leading ME/CFS, Long-Covid, and fibromyalgia research center in Salt Lake City, Utah.

Dr. Ruoyun Xiong, also a lead author on the study, developed a deep neural network model called BioMapAI. The tool integrates gut metagenomics, plasma metabolomics, immune cell profiles, blood test data, and clinical symptoms from 153 patients and 96 healthy individuals over four years.

Immune cell analysis proved most accurate in predicting symptom severity, while microbiome data best predicted gastrointestinal, emotional, and sleep disturbances. The model connected thousands of patient data points, reconstructing symptoms such as pain and gastrointestinal issues, among several others.

It also revealed that patients who were ill for less than four years had fewer disrupted networks than those who were ill for more than  ten years. “Our data indicate these biological disruptions become more entrenched over time,” Unutmaz said. “That doesn’t mean longer-duration ME/CFS can’t be reversed, but it may be more challenging.”The study included 96 age- and gender-matched healthy controls, showing balanced microbiome-metabolite-immune interactions, in contrast to significant disruptions in ME/CFS patients linked to fatigue, pain, emotional regulation issues, and sleep disorders.ME/CFS patients also had lower levels of butyrate, a beneficial fatty acid produced in the gut, along with other nutrients essential for metabolism, inflammation control, and energy.

Patients with elevated levels of tryptophan, benzoate, and other markers indicated a microbial imbalance. Heightened inflammatory responses, particularly involving MAIT cells sensitive to gut microbial health, were also observed.

“MAIT cells bridge gut health to broader immune functions, and their disruption alongside butyrate and tryptophan pathways, normally anti-inflammatory, suggests a profound imbalance,” said Unutmaz.

An Actionable Dataset Even though the findings require further validation, they significantly advance scientists’ understanding of ME/CFS and provide clearer hypotheses for future research, the authors said.

Since animal models can’t fully reflect the complex neurological, physiological, immune, and other system disruptions seen in ME/CFS, Oh said it will be crucial to study humans directly to identify modifiable factors and develop targeted treatments.

“The microbiome and metabolome are dynamic,” Oh said. “That means we may be able to intervene—through diet, lifestyle, or targeted therapies—in ways that genomic data alone can’t offer.”

BioMapAI also achieved roughly 80% accuracy in external data sets, confirming key biomarkers identified in the original group. This consistency across diverse data was striking, the authors said.

“Despite diverse data collection methods, common disease signatures emerged in fatty acids, immune markers, and metabolites,” Oh said. “That tells us this is not random. This is real biological dysregulation.”

The researchers intend to share their dataset broadly with BioMapAI, which supports analyses across diverse symptoms and diseases, effectively integrating multi-omics data that are difficult to replicate in animal models.

“Our goal is to build a detailed map of how the immune system interacts with gut bacteria and the chemicals they produce,” Oh said.

“By connecting these dots we can start to understand what’s driving the disease and pave the way for genuinely precise medicine that has long been out of reach.” 

Additional authors include Elizabeth Aiken, Ryan Caldwell, Lina Kozhaya, and Courtney Gunter (The Jackson Laboratory), and Suzanne D. Vernon and Lucinda Bateman (Bateman Horne Center).

Funding: Funding was provided by NIH grant 1U54NS105539.

About this chronic fatigue and microbiome research news

Author: Cara McDonough
Source: Jackson Laboratory
Contact: Cara McDonough – Jackson Laboratory
Image: The image is credited to Neuroscience News

Original Research: Closed access.
“AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome” by Derya Unutmaz et a;. Nature Medicine

---

Abstract

AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness with a multifactorial etiology and heterogeneous symptomatology, posing major challenges for diagnosis and treatment.

Here we present BioMapAI, a supervised deep neural network trained on a 4-year, longitudinal, multi-omics dataset from 249 participants, which integrates gut metagenomics, plasma metabolomics, immune cell profiling, blood laboratory data and detailed clinical symptoms. Biomarkers and classifies ME/CFS in both held-out and independent external cohorts.

Using an explainable AI approach, we construct a unique connectivity map spanning the microbiome, immune system and plasma metabolome in health and ME/CFS adjusted for age, gender and additional clinical factors.

This map uncovers altered associations between microbial metabolism (for example, short-chain fatty acids, branched-chain amino acids, tryptophan, benzoate), plasma lipids and bile acids, and heightened inflammatory responses in mucosal and inflammatory T cell subsets (MAIT, γδT) secreting IFN-γ and GzA.

Overall, BioMapAI provides unprecedented systems-level insights into ME/CFS, refining existing hypotheses and hypothesizing unique mechanisms—specifically, how multi-omics dynamics are associated to the disease’s heterogeneous symptoms.

Study Reveals Turning Point When Your Body's Aging Accelerates

 Will your competent? doctor get further human testing going to come up with a solution? Your doctor has done nothing in the past, why start now? My brain aging dropped off a cliff at age 50 instead of 55 in the diagram, so trying to be number 1 in that category.

Study Reveals Turning Point When Your Body's Aging Accelerates

he passage of time may be linear, but the course of human aging is not. Rather than a gradual transition, your life staggers and lurches through the rapid growth of childhood, the plateau of early adulthood, to an acceleration in aging as the decades progress.

Now, a new study has identified a turning point at which that acceleration typically takes place: at around age 50.

After this time, the trajectory at which your tissues and organs age is steeper than the decades preceding, according to a study of proteins in human bodies across a wide range of adult ages – and your veins are among the fastest to decline.

"Based on aging-associated protein changes, we developed tissue-specific proteomic age clocks and characterized organ-level aging trajectories. Temporal analysis revealed an aging inflection around age 50, with blood vessels being a tissue that ages early and is markedly susceptible to aging," writes a team led by scientists from the Chinese Academy of Sciences.

"Together, our findings lay the groundwork for a systems-level understanding of human aging through the lens of proteins."

Related: Study Finds Humans Age Faster at 2 Sharp Peaks – Here's When

Humans have a remarkably long lifespan compared to most other mammals, but it comes at some costs. One is a decline in organ function, leading to a rise in risk of chronic disease as the years mount up.

We don't have a very good understanding of the patterns of aging in individual organs, so the researchers investigated how proteins in different tissues change over time. They collected tissue samples from a total of 76 organ donors between the ages of 14 and 68 who had died of accidental traumatic brain injury.

These samples covered seven of the body's systems: cardiovascular (heart and aorta), digestive (liver, pancreas, and intestine), immune (spleen and lymph node), endocrine (adrenal gland and white adipose), respiratory (lung), integumentary (skin), and musculoskeletal (muscle). They also took blood samples.

The team constructed a catalogue of the proteins found in these systems, taking careful note of how their levels changed as the ages of the donors increased. The researchers compared their findings to a database of diseases and their associated genes, and found that expressions of 48 disease-related proteins increased with age.

These included cardiovascular conditions, tissue fibrosis, fatty liver disease, and liver-related tumors.

The most stark changes occurred between the ages of 45 and 55, the researchers found. It's at this point that many tissues undergo substantial proteomic remodeling, with the most marked changes occurring in the aorta – demonstrating a strong susceptibility to aging. The pancreas and spleen also showed sustained change.

Your body's organs according to ages they're most sensitive to aging. (Ding et al., Cell, 2025)

To test their findings, the researchers isolated a protein associated with aging in the aortas of mice, and injected it into young mice to observe the results. Test animals treated with the protein had reduced physical performance, decreased grip strength, lower endurance, and lower balance and coordination compared to non-treated mice. They also had prominent markers of vascular aging.

Previous work by other researchers showed another two peaks in aging, at around 44, and again at around 60. The new result suggests that human aging is a complicated, step-wise process involving different systems. Working out how aging is going to affect specific parts of the body at specific times could help develop medical interventions to make the process easier.

"Our study is poised to construct a comprehensive multi-tissue proteomic atlas spanning 50 years of the entire human aging process, elucidating the mechanisms behind proteostasis imbalance in aged organs and revealing both universal and tissue-specific aging patterns," the researchers write.

"These insights may facilitate the development of targeted interventions for aging and age-related diseases, paving the way to improve the health of older adults."

The research has been published in Cell.

Caffeine in Aging Brains: Cognitive Enhancement, Neurodegeneration, and Emerging Concerns About Addiction

 

I'm doing it to increase my healthspan, lower my chances of dementia and Parkinsons.

 If you provide research that tells me 3-4  cups a day reduces dementia and Parkinson's risk, then I'll change my habit, but until then this is occurring:

Research suggests caffeine is not the main reason for these other benefits, go ask your incompetent doctor for clarification.

Like Your Coffee Black? Congratulations, You Could Be a Psychopath I need to add milk

How coffee protects against Parkinson’s Aug. 2014 

Coffee May Lower Your Risk of Dementia Feb. 2013

Coffee drinkers rejoice! Drinking coffee could lower the risk of Alzheimer’s disease 

And this: Coffee's Phenylindanes Fight Alzheimer's Plaque December 2018

New research suggests drinking coffee may reduce the risk of frailty May 2025

I think I'm in this category:  I never get the jitters or flushed skin.

Genetics determine how much coffee you can drink before it goes wrong

I'm doing a 12 cup pot of coffee a day with full fat milk to lessen my chances of dementia and Parkinsons. Tell me EXACTLY how much coffee to drink for that and I'll change. Yep, that is a lot more than the 400mg. suggested limit, I don't care! Preventing dementia and Parkinsons is vastly more important than whatever problems it can cause! 

coffee (361 posts to February 2012)

The latest here:

Caffeine in Aging Brains: Cognitive Enhancement, Neurodegeneration, and Emerging Concerns About Addiction

by 

Manuel Glauco Carbone

 1,2,3,

Giovanni Pagni

 4,

Claudia Tagliarini

 5,

Icro Maremmani

 2,3,* and

Angelo Giovanni Icro Maremmani

 2,3

1

Division of Psychiatry, Department of Medicine and Surgery, University of Insubria, Viale Luigi Borri 57, 21100 Varese, Italy

2

VP Dole Research Group, G. De Lisio Institute of Behavioural Sciences, Via di Pratale 3, 56121 Pisa, Italy

3

Saint Camillus International University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy

4

Department of Psychiatry, North-Western Tuscany Local Health Unit, Tuscany NHS, Lunigiana Socio-Sanitary Area, Piazza Craxi 22, 54011 Aulla, Italy

5

Psychiatric Diagnosis and Treatment Service (S.P.D.C.), Sant’Elia Hospital, Provincial Health Authority 2, Via Luigi Russo 6, 93100 Caltanissetta, Italy

*

Author to whom correspondence should be addressed.

Int. J. Environ. Res. Public Health 2025, 22(8), 1171; https://doi.org/10.3390/ijerph22081171

Submission received: 20 June 2025 / Revised: 18 July 2025 / Accepted: 21 July 2025 / Published: 24 July 2025

(This article belongs to the Section Behavioral and Mental Health)

Downloadkeyboard_arrow_down Versions Notes

Abstract

This narrative review examines the effects of caffeine on brain health in older adults, with particular attention to its potential for dependence—an often-overlooked issue in geriatric care. Caffeine acts on central adenosine, dopamine, and glutamate systems, producing both stimulating and rewarding effects that can foster tolerance and habitual use. Age-related pharmacokinetic and pharmacodynamic changes prolong caffeine’s half-life and increase physiological sensitivity in the elderly. While moderate consumption may enhance alertness, attention, and possibly offer neuroprotective effects—especially in Parkinson’s disease and Lewy body dementia—excessive or prolonged use may lead to anxiety, sleep disturbances, and cognitive or motor impairment. Chronic exposure induces neuroadaptive changes, such as adenosine receptor down-regulation, resulting in tolerance and withdrawal symptoms, including headache, irritability, and fatigue. These symptoms, often mistaken for typical aging complaints, may reflect a substance use disorder yet remain under-recognized due to caffeine’s cultural acceptance. The review explores caffeine’s mixed role in neurological disorders, being beneficial in some and potentially harmful in others, such as restless legs syndrome and frontotemporal dementia. Given the variability in individual responses and the underestimated risk of dependence, personalized caffeine intake guidelines are warranted. Future research should focus on the long-term cognitive effects and the clinical significance of caffeine use disorder in older populations.

Keywords: 

caffeine dependence; neurodegenerative diseases; cognitive impairment; elderly

1. Introduction

The consumption of caffeine among the elderly represents a complex issue that warrants careful and nuanced examination. While it is acknowledged that caffeine intake can confer certain benefits, it is equally important to evaluate potential risks and the heightened sensitivity that this age group may develop. Caffeine is not solely found in coffee; it is also present in tea, chocolate, energy drinks, and even in some pharmaceuticals, which contributes to its widespread exposure across populations [1,2]. For the purposes of clarity and consistency in this review, we will use the term “elderly people” to refer to individuals aged 65 years or older, a definition that aligns with criteria commonly used by the World Health Organization (WHO) and in numerous studies in the field of geriatrics. It is important to acknowledge, however, that a universally accepted definition of “elderly” does not exist, and that the studies included in this review may employ varying age-based inclusion criteria (e.g., 60 years and older). We recognize that this variability could be a limitation when interpreting and comparing research findings.

In older adults, the metabolism of caffeine tends to slow, leading to prolonged biological half-life and amplification of its effects, thus necessitating a cautious approach to consumption [3].

A key factor contributing to this prolonged half-life is the age-related decline in metabolic rate. However, compromised renal function can further impair the clearance of caffeine metabolites, exacerbating this effect in older adults. Supporting the influence of genetic factors and their association with kidney function, recent research [4,5] has confirmed these relationships. Furthermore, a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES)—a nationally representative survey assessing the health and nutritional status of adults and children in the United States—by Gao et al. (2025) [6] highlighted an inverse association between the consumption of coffee, tea, and caffeine and the presence of CKD, further reinforcing the potential protective role of these dietary habits on renal health.

Moderate caffeine intake has generally been associated with cognitive benefits in elderly individuals, including improvements in short-term memory, attention, and verbal fluency [7,8,9]. Nonetheless, with advancing age, sensitivity to caffeine appears to increase, consequently elevating the risk of adverse effects [10]. These include sleep disturbances, heightened anxiety, gastrointestinal issues, cardiovascular problems, and an increased likelihood of developing osteoporosis [11,12,13,14,15]. Moreover, age-related decline in renal function, coupled with reduced hydration status and potential interactions with polypharmacy, may exacerbate adverse outcomes related to caffeine consumption [16,17,18].

Therefore, a careful assessment of caffeine intake is essential in elderly populations, considering individual health conditions, comorbidities, and medication regimens to balance potential benefits against risks accurately. An often underestimated aspect is the potential for dependence; even in late adulthood, habitual consumers may develop caffeine dependence, with abrupt reduction potentially provoking withdrawal symptoms, such as headaches, fatigue, and irritability [19,20,21].

The prevalence of caffeine consumption among older adults is considerable and warrants attentive awareness from healthcare professionals. Epidemiological studies have demonstrated that a significant proportion of individuals over 65 years consume caffeine regularly [22,23,24]. For instance, a 2018 survey conducted by the National Sleep Foundation reported that approximately 40% of Americans aged between 65 and 79, and about 35% of those aged 80 and above, consume caffeine on a daily basis [25,26,27]. Although research specifically targeting caffeine dependence in older populations remains limited, some evidence suggests that the risk of developing dependence may increase with age, particularly after 60 years [21,28,29,30,31]. This trend could be attributed to factors like decreased metabolic rate and physiological changes in body composition, which may render older adults more susceptible to the stimulating effects of caffeine [32,33].

Caffeine consumption is also widespread within the Italian elderly population, although data indicate that prevalence decreases with age [34]. A survey by the Italian National Institute of Statistics revealed that around 70% of Italians aged between 65 and 74 drink coffee daily [35]. Notably, compared to US figures, Italians tend to consume higher quantities of caffeine overall [36,37]. Nonetheless, it appears that elderly Italians may have a lower propensity to develop caffeine dependence compared to their American counterparts, possibly due to cultural differences in consumption patterns and genetic factors influencing caffeine metabolism [21,38,39,40]. It is important to acknowledge that environmental factors, particularly climate and humidity, can influence renal capacity and hydration, potentially impacting caffeine metabolism [41,42]. While these factors may contribute to population-level differences in caffeine sensitivity, definitive evidence remains limited.

To further elucidate individual variability, we considered research on genetic variations influencing caffeine metabolism. Studies have shown that CYP1A2 rs762551 AC/CC genotypes (associated with slower caffeine metabolism) are linked to increased risks of albuminuria, hyperfiltration, and hypertension with high coffee intake [43], supporting a genetic predisposition. These findings align with research demonstrating that CYP1A2 polymorphism impacts athletic performance [44,45], suggesting a broader influence on individual responses to caffeine. The interplay between climate, genetics, and individual factors likely shapes the complex response to caffeine, highlighting the need for personalized recommendations.

This narrative review aims to critically examine the role of caffeine in brain health among older adults, with a focus on its pharmacological mechanisms, cognitive and motor effects, potential neuroprotective properties in neurodegenerative diseases, and the often-overlooked issue of dependence. By integrating findings across diverse neurological domains, this review seeks to inform clinical awareness and public health strategies for safe and personalized caffeine consumption in later life.

2. Review Results

This narrative review presents an integrated synthesis of current evidence regarding the effects of caffeine on brain health in older adults. The findings are organized into thematic sections to reflect the most clinically and biologically relevant domains.

First, the pharmacokinetic and pharmacodynamic characteristics of caffeine are reviewed, with particular attention to age-related changes that influence its absorption, metabolism, and action on adenosine, dopamine, and glutamate systems. These mechanisms underpin both the stimulant effects of caffeine and its potential to induce tolerance and dependence.

The review then explores the neurobiological basis of caffeine dependence, including receptor adaptations and withdrawal syndromes, which remain under-recognized in elderly populations. Following this, the role of caffeine in various neurological and neurodegenerative conditions is assessed. In movement disorders, such as Parkinson’s disease and essential tremor, as well as in conditions like multiple sclerosis and Tourette’s syndrome, caffeine shows a spectrum of effects ranging from potentially protective to symptom-aggravating depending on dose, disease type, and individual sensitivity.

Attention is also given to caffeine’s influence on cognitive domains, including memory, attention, and executive function, as well as its debated role in age-related cognitive decline. Finally, the review evaluates emerging evidence of caffeine’s impact on major neurodegenerative diseases, including Alzheimer’s disease, vascular dementia, frontotemporal dementia, and Lewy body dementia.

Together, these results highlight a complex and sometimes contradictory profile of caffeine in later life, necessitating a personalized and cautious approach to its use.

2.1. Effects of Caffeine on the Brain: Pharmacokinetics and Pharmacodynamics

Caffeine, a psychoactive compound classified within the methylxanthine group, is widely consumed for its stimulant properties. Its pharmacological activity is intrinsically linked to its trajectory within the body, from absorption to elimination. The absorption of caffeine occurs rapidly, primarily through the gastrointestinal tract, with plasma concentrations reaching their peak approximately 30 to 60 min post-ingestion. Once in circulation, caffeine rapidly disseminates across tissues, including the central nervous system, due to its ability to cross the blood–brain barrier. The hepatic metabolism of caffeine plays a central role, principally mediated by the enzyme CYP1A2, a member of the cytochrome P450 system. This process generates active metabolites, including paraxanthine, theobromine, and theophylline, which contribute to the overall psychoactive effects. Renal excretion is the main pathway for the elimination of caffeine and its metabolites, with the half-life varying significantly among individuals due to factors like age, hepatic and renal function, smoking, and concurrent medication use [46,47,48,49]. In older adults, significant pharmacokinetic changes occur that warrant special attention. Hepatic metabolism, primarily through CYP1A2, declines with age, leading to slower clearance of caffeine [50,51,52,53]. Studies have shown that the half-life of caffeine can increase from 3–5 h in young adults to 6–10 h or more in older adults [19,54]. Reduced renal function further impairs the excretion of caffeine metabolites, prolonging their presence in the body [3,4,11,55]. Consequently, the same dose of caffeine can result in higher plasma concentrations and a greater risk of adverse effects in older adults.

As previously said, it is essential to underscore that individual response to caffeine is highly subjective and can be influenced by genetic predispositions, such as variants of the CYP1A2 gene, as well as physiological states, including pregnancy and aging [50,55,56,57]. In particular, aging-related changes can prolong caffeine’s half-life and heighten susceptibility to adverse effects, underscoring the importance of personalized consumption guidelines [46]. Therefore, healthcare providers should consider these age-related pharmacokinetic changes when recommending caffeine intake to older adults, carefully assessing potential interactions with medications and existing health conditions [2,58].

Caffeine exerts its primary pharmacodynamic effects mainly through antagonism of adenosine receptors in the central nervous system. Adenosine, an inhibitory neurotransmitter, accumulates during wakefulness, promoting relaxation and preparing the brain for sleep. Structurally similar to adenosine, caffeine binds to these receptors without activating them, functioning as a competitive antagonist. This blockade reduces the inhibitory influence of adenosine, thereby increasing arousal, alertness, and cognitive performance. Caffeine exhibits high affinity particularly for the A1 and A2A adenosine receptor subtypes [59,60,61].

The antagonism of A1 receptors, predominantly located in the hippocampus, cerebral cortex, and basal ganglia, facilitates the release of excitatory neurotransmitters, such as dopamine, acetylcholine, and glutamate. These mechanisms help explain caffeine’s stimulant effects on cognitive functions, mood, and vigilance [62,63,64,65,66]. Meanwhile, blocking A2Areceptors, mainly expressed in cerebral vasculature and the striatum, contributes to caffeine’s vasoconstrictive properties and influences motor control. Moreover, inhibition of A2Areceptors in the striatum enhances dopamine release, underpinning caffeine’s rewarding properties and its potential for dependence [67,68,69,70,71,72,73].

Beyond direct receptor interaction, caffeine modulates dopaminergic and cholinergic systems by increasing dopamine release and inhibiting its reuptake at the synaptic level, largely via antagonism of A2Areceptors [74,75,76]. The resultant elevation of dopaminergic activity in the striatum, a key brain area involved in motivation, reward, and executive function, contributes to enhanced mood, motivation, and cognitive performance [77,78]. However, this same mechanism also underpins the development of tolerance and dependence.

Additionally, caffeine influences the cholinergic system by promoting the release of acetylcholine in several brain regions, including the prefrontal cortex and the hippocampus. This effect is mainly mediated by the inhibition of A1 adenosine receptors and plays a significant role in facilitating cognitive processes, such as attention, learning, and memory [11,49].

2.2. Neurobiological Mechanisms of Caffeine Dependence: From Neurotransmitter Systems to Motor and Cognitive Circuits

Chronic caffeine consumption induces neuroadaptive changes that lead to tolerance and dependence. The brain, continually exposed to caffeine’s antagonistic effects on adenosine receptors, activates compensatory mechanisms to preserve homeostasis. One such mechanism is receptor down-regulation, characterized by a reduction in the number of adenosine A1 and A2Areceptors on neuronal cell surfaces. This decrease diminishes the brain’s sensitivity to caffeine’s effects, necessitating higher doses to achieve the same stimulating response. Such adaptation underpins the development of tolerance, whereby increasing amounts of caffeine are required to produce desired effects [79,80,81,82].

Abrupt cessation or significant reduction of caffeine intake following prolonged habitual use can precipitate withdrawal symptoms [83]. This occurs because the suppression of adenosine’s inhibitory action is no longer present, leading to a rebound effect. Withdrawal symptoms typically expressed are listed below.

Headache: Adenosine acts as a vasodilator; caffeine’s vasoconstrictive effect contributes to headaches upon discontinuation due to sudden vasodilation.

Fatigue and drowsiness: Without caffeine’s antagonism, adenosine binds to its receptors, promoting sleepiness and impaired concentration.Irritability, anxiety, and depressive symptoms: Caffeine elevates dopamine and other mood-related neurotransmitter levels; withdrawal can cause a chemical imbalance, resulting in symptoms of mood and anxiety disorders.Cognitive difficulties and psychomotor slowing: Caffeine enhances alertness and cognitive functions; withdrawal reduces these capabilities, leading to concentration deficits and slowed processing.

Physical symptoms: Nausea, vomiting, and muscle pain are also reported [19,20,56,83,84,85,86].

Manifestations of caffeine dependence in the elderly may present unique challenges for clinical identification. While the core withdrawal symptoms remain consistent with younger populations, their presentation can be masked or misinterpreted due to the higher prevalence of comorbid conditions and age-related physiological changes [85,87,88,89]. For instance, fatigue, a common withdrawal symptom, can be easily attributed to the natural aging process or underlying medical conditions, such as anemia, endocrinopathies, or different metabolic disorders [90]. Similarly, headaches may be dismissed as tension headaches or attributed to medication side effects [91,92]. Irritability and anxiety may be misconstrued as symptoms of various neuropsychiatric disorders, including primary anxiety disorders, mood disorders, or early manifestations of a neurodegenerative condition [93,94].

Furthermore, the cognitive enhancing effects of caffeine can lead to a cycle of dependence, with older adults using caffeine to counteract age-related cognitive decline or fatigue, unknowingly perpetuating their dependence. This can make it difficult to distinguish between caffeine withdrawal symptoms and underlying cognitive impairment.

Clinical identification of caffeine dependence in the elderly requires a thorough assessment, including a detailed history of caffeine intake, a careful evaluation of other potential causes for their symptoms, and a high index of suspicion. Questionnaires designed to assess caffeine dependence, such as the Caffeine Use Disorder Questionnaire (CUDQ), may be useful in identifying problematic caffeine use [95], but their validity in older adults needs further investigation. Clinicians should also be aware of the potential for underreporting of caffeine consumption due to social stigma or lack of awareness [96,97].

Given the potential for misdiagnosis and the negative impact of caffeine dependence on health outcomes, clinicians should consider routine screening for caffeine use and dependence in older adults, particularly those presenting with unexplained fatigue, anxiety, or cognitive complaints. Strategies to manage caffeine dependence in older adults include gradual caffeine reduction, behavioral therapies, and management of comorbid conditions [21,98].

While caffeine does not directly bind to dopaminergic receptors, it indirectly activates the brain’s reward circuits, particularly the mesolimbic dopamine pathway. Originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens, amygdala, and prefrontal cortex, this system mediates feelings of pleasure, motivation, and associative learning [75]. Caffeine’s blockade of A2Aadenosine receptors in the striatum enhances dopamine release in the nucleus accumbens, producing pleasure and positive reinforcement that contribute to repeated consumption and dependence development.

The rewarding and cognitive-enhancing effects of caffeine are largely mediated through the increased release of excitatory neurotransmitters, including dopamine, acetylcholine, and glutamate, via the antagonism of adenosine receptors [99]. This mechanism explains caffeine’s efficacy in improving vigilance, attention, memory, and executive functions. However, this stimulatory effect can become self-perpetuating, as dependence develops as individuals seek to maintain optimal cognitive performance, fostering a vicious cycle. Tolerance to caffeine’s cognitive effects may drive increased intake, culminating in dependence and withdrawal symptoms, such as headache, fatigue, and irritability, upon attempts to reduce consumption [100].

Long-term habitual caffeine intake may lead to significant neurophysiological alterations, with potential negative consequences for cognitive function and motor control. Prolonged caffeine exposure induces down-regulation of adenosine receptors, resulting in modifications across several brain regions described below [65,77,101].

Prefrontal cortex (PFC): The PFC is critical for executive functions, working memory, decision making, and attention. The PFC shows increased activity initially with caffeine due to elevated levels of dopamine and acetylcholine. Chronic use, however, can lead to dopamine receptor down-regulation, impairing cognitive efficiency, reducing cognitive flexibility, and increasing impulsivity.

Hippocampus: Essential for episodic memory formation and learning, caffeine’s acute effects may enhance short-term memory; however, long-term intake can interfere with synaptic plasticity, which is necessary for long-term memory consolidation, potentially impairing learning and memory retention.

Amygdala: Involved in emotion regulation, particularly fear and anxiety, caffeine may augment amygdala activity, heightening stress responses and anxiety, especially in predisposed individuals. Chronic use may contribute to hyperactivity of this region, exacerbating anxiety and irritability, notably during caffeine withdrawal.

Striatum: Caffeine influences motor control primarily through antagonism of A2Areceptors in the striatum, a pivotal structure in voluntary movement regulation [102,103,104,105,106]. Persistent caffeine intake can cause desensitization of dopaminergic receptors in the striatum, diminishing its initial positive effects on motor coordination. Manifestations may include decreased movement precision, tremors, impaired coordination, and slowed reaction times.

Cerebellum: This structure, integral for fine motor coordination, balance, and motor learning, may also be affected indirectly by caffeine-induced dopaminergic alterations, potentially contributing to deficits in balance and coordination. Although direct studies are limited, the neuroadaptive changes in dopaminergic pathways suggest that long-term caffeine consumption could subtly impair motor functions.

In summary, sustained caffeine intake can induce widespread alterations in neural activity across multiple brain regions, with potential adverse effects on cognitive and motor functions. It is crucial to recognize that individual sensitivity to caffeine, dosing patterns, and duration of use significantly modulate these neurophysiological responses, emphasizing the importance of personalized assessment and cautious consumption in vulnerable populations.

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