Given the despicable state of nutrition research, what do you think of the plan to add 40 h of nutritional study to med school? It mght be marginally better than present where many physicians appear to get their information from popular media. Might be worse as the training may give the patina of rigor to the material.
The claim that coffee consumption reduces dementia risk based on the JAMA article is not inherently inaccurate, but it is incomplete due to key limitations inherent to observational studies. Study group strongly biased due to subjects being primarily white, educated, financially secure. The research shows a strong association, however the study cannot prove causation—it does not confirm that caffeine directly prevents dementia.
Key reasons the claim is incomplete:
No proof of causation: The study is observational. While it adjusted for many factors (diet, genetics, lifestyle), unmeasured confounders—such as overall health habits or socioeconomic status—could influence results.
Dementia prevalence in the United States varies significantly by race and age, with higher rates observed among older adults and certain racial and ethnic groups.
Age is the strongest risk factor for dementia. Prevalence increases sharply with age:
3% of adults aged 65–69 have dementia.
Rates rise to 35% among those aged 90 and older.
Race and Ethnicity:
Black or African American adults have the highest dementia prevalence (15%), followed by Hispanic/Latino adults (10%), and White adults (9%).
Black individuals also face the highest incidence rates, with 4.2% in 2015, decreasing to 3.1% by 2021.
Hispanic incidence declined from 3.7% to 2.6% over the same period.
White incidence decreased from 3.4% to 2.8% (this might be the real flaw in the study).
Despite declines, Black and Hispanic populations still have higher rates than White populations, though the gap has narrowed over time.
Education is a key factor: those with less than a high school education have a dementia prevalence of 13%, compared to 9% for those with a college degree or higher.
These disparities are linked to structural and social inequalities, including differences in access to healthcare, cardiovascular health, and lifelong socioeconomic conditions.
Sorry to hear that a strong intelligent voices (Alex B as well as J. Childers) can fall prey to propaganda (sole existence of JAMA, IMO).
Thx for your post and deep(er) perspective than others.
Very, very well said. I do wonder how many of those 45,000-85,000 observational studies did come from Harvard. I'm guessing a lot. If so, that would based a lot of the published observational nutrition research in the hands of one institution and base it on their tool, the FFQ, which may not be the best, but that's another post. IMHO.
One of the challenges with studies like this isn’t the observational design itself — it’s how quickly modest associations get amplified into lifestyle prescriptions. Relative risk reductions become headlines, nuance disappears, and no one revisits the claim years later when outcomes don’t match expectations.
Some articles approve fantastic properties of coffee drinking.. others dissaprove intake and associate it with dementia & other ailments. I am a 76 yr old Cardiologist in general practice, and I consume 2 -3 cups of this brain energizer during the morning and sometimes on discussions with colleagues in the same coffee sharing. We are al around the same age. we are not pursuing to leave our most enjoyful drink in tne mornings, articles or no article... Respectfully. .
In reference to your February 16 Sensible Medicine post, “Coffee is great but it does not prevent dementia,” I would like to offer a brief semantic and epistemological reflection.
First, a confession of origin: I come from a latitude where some claim the world’s most aromatic coffee is grown. I will nonetheless attempt intellectual sobriety.
Semantically, in epidemiology, few exposures “prevent” disease in an absolute sense. They modify probabilities. Thus, stating that coffee does not prevent dementia is technically correct if prevention implies total risk abolition. But the relevant question is whether moderate consumption reduces baseline risk—and by how much.
The study by Zhang et al. (2021), using UK Biobank data, reported non-linear associations between moderate coffee (and tea) intake and lower risk of stroke and dementia, with lowest risk around 2–3 cups daily. The authors claimed association, not causation. Their methodological caution was clear.
It is also true that long-term randomized controlled trials (RCTs) showing that coffee prevents incident dementia do not exist. But neither do such RCTs for walking every morning. Chronic disease epidemiology rarely allows decades-long molecularly isolated interventions with clinical endpoints.
Here lies the deeper issue.
Much research in cardiovascular disease and dementia has been framed within linear pathogenic models—lipid accumulation, metabolic overflow, amyloid deposition. RCTs inherit these ontologies. Randomization reduces allocation bias, but it does not correct the conceptual framing of disease as a single-pathway excess requiring molecular subtraction.
Chronic disease, however, is systemic, adaptive, and contextual.
Umbrella reviews by Poole et al. (2017) and Grosso et al. (2017) showed consistent inverse associations between moderate coffee consumption and all-cause mortality, cardiovascular disease, type 2 diabetes, liver disease, Parkinson’s disease, and depression—greatest around 3–4 cups daily. More recent syntheses (e.g., Gill et al., 2024; Ungvari et al., 2024) continue to report favorable associations with cardiometabolic health and plausible mechanisms involving insulin sensitivity, endothelial function, and inflammation—while acknowledging predominantly observational evidence.
Consistency and biological plausibility appear present; magnitude of independent causality remains debated.
Perhaps, however, the debate is misframed.
From a salutogenic perspective, the morning cup is not merely caffeine and polyphenols. It is a ritual embedded in circadian timing, social interaction, mood regulation, and behavioral organization. Dementia—particularly vascular and Alzheimer-type—shares substrates with cardiometabolic deterioration, chronic inflammation, endothelial dysfunction, and circadian disruption. In that broader system, coffee may act less as an isolated neuroprotective agent and more as a behavioral marker within a coherent metabolic ecology.
It is not the cup alone. It is the system in which the cup is embedded.
Rather than asking whether coffee prevents dementia, perhaps the better question is: within what biological and social metabolism do we place that daily cup? There—in the organization of the system—is where prevention may truly reside.
References
Echeverry-Raad, J. (2024). A falsehood that has been repeated many times becomes true: The origin of the diabesity pandemic, the most lethal of the 21st century? Journal of Diabetes, Metabolic Disorders & Control, 11(1), 39–50. https://doi.org/10.15406/jdmdc.2024.11.00276
Gill, D., et al. (2024). An umbrella review of meta-analyses to understand the effect of coffee consumption and the relationship between stroke, cardiovascular heart disease, and dementia. [Publication details pending].
Grosso, G., Godos, J., Galvano, F., & Giovannucci, E. L. (2017). Coffee, caffeine, and health outcomes: An umbrella review. Annual Review of Nutrition, 37, 131–156. https://doi.org/10.1146/annurev-nutr-071816-064941
Poole, R., Kennedy, O. J., Roderick, P., Fallowfield, J. A., Hayes, P. C., & Parkes, J. (2017). Coffee consumption and health: Umbrella review of meta-analyses of multiple health outcomes. BMJ, 359, j5024. https://doi.org/10.1136/bmj.j5024
Ungvari, Z., et al. (2024). Coffee consumption and cardiometabolic health. [Publication details pending].
Zhang, Y., Yang, H., Li, S., Li, W. D., & Wang, Y. (2021). Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLoS Medicine, 18(11), e1003830. https://doi.org/10.1371/journal.pmed.1003830
Mandrola nails the core problem here: an observational association is being marketed as a preventive intervention, and the confidence of the coverage is wildly out of proportion to what the design can support. 
A few things I’d underline as a physician-scientist:
1. Your Bayesian prior should be low. Dementia is a heterogeneous syndrome (vascular, neurodegenerative, inflammatory, toxic, genetic), so the idea that one exposure like coffee would cleanly “prevent dementia” should trigger skepticism before you even look at a p-value. 
2. Adjustment is not randomization. You can only adjust for what’s captured, and “coffee drinker” is a cluster label for countless health, socioeconomic, sleep, work-pattern, and behavioral differences that don’t fit neatly in a spreadsheet. 
3. Effect-size + subgroup results are a tell. When a simple habit shows an ~18% lower dementia risk overall and looks even “better” in age strata, that’s often the signature of residual confounding/selection effects rather than biology doing something magical. 4. Analytic flexibility is the quiet elephant. With enough plausible modeling choices, you can often “find” a publishable association, especially in nutrition/behavior epidemiology, without anyone committing fraud. 
Enjoy coffee if you enjoy coffee. But if we’re serious about dementia prevention, we should keep the spotlight on interventions with stronger causal footing (BP control, physical activity, sleep, hearing, metabolic risk, smoking, education/cognitive engagement), not another headline that confuses correlation with protection.
All good with doubting observational data. If only people would do it consistently (ahemmm...vaccines...). But the claimed effect here with coffee is entirely plausible. This is what happens when you go to medical school and don't understand pleiotropy of natural medicines and experience supplements as an alternate dimension. No offense, but it's true.
A reflexive negative reaction to observational studies is itself a cognitive bias.
Observational and epidemiological studies are perfectly good puzzle pieces. The fixation on blinded controlled studies is not helpful. Those are great too, and in some ways better. But they can never cover the same size population or duration. All forms of evidence are imperfect.
In this particular case, the protective effects of caffeine have been seen in multiple observational studies over the years, enough that it should not be ignored. If there were no mechanism explaining why this effect would work, it would be a little shaky (though still valid-though-imperfect evidence). But there is an excellent, well supported, mechanism.
Studies demonstrate that, in mice caffeine and Eicosanoyl-5-hydroxytryptamide (EHT), which is found in coffee beans work together to improve activity of the PP2A catalyst, which protects the brain against abnormal protein accumulation. Studies in mice showed that the combination of EHT and caffeine reduced neuroinflammation and protected against oxidative stress, and manifested in actual effects in behavior.
"But that's just mice, not people."
No. When you have an observational study, a very plausible mechanism, and demonstrated efficacy in mice, that adds up to solid evidence. Is it enough to approve a drug? Maybe not. But is it enough to make it reasonable for people to take it seriously? Yes.
"Good enough for drug approval" is not the same thing as "good enough to incorporate into your personal practices."
This will inevitably be used frequently on an individual level (not saying JAMA or authors are suggesting this) to justify unhealthy high calorie coffee consumption with abundantly added sugar and creamer.
Given the despicable state of nutrition research, what do you think of the plan to add 40 h of nutritional study to med school? It mght be marginally better than present where many physicians appear to get their information from popular media. Might be worse as the training may give the patina of rigor to the material.
In capital markets, money can buy legitimacy. You’ve changed my view of all the white papers I’ve ever read. Damn you John.
At least it didn't hurt anything!
Per A.I.:
The claim that coffee consumption reduces dementia risk based on the JAMA article is not inherently inaccurate, but it is incomplete due to key limitations inherent to observational studies. Study group strongly biased due to subjects being primarily white, educated, financially secure. The research shows a strong association, however the study cannot prove causation—it does not confirm that caffeine directly prevents dementia.
Key reasons the claim is incomplete:
No proof of causation: The study is observational. While it adjusted for many factors (diet, genetics, lifestyle), unmeasured confounders—such as overall health habits or socioeconomic status—could influence results.
Dementia prevalence in the United States varies significantly by race and age, with higher rates observed among older adults and certain racial and ethnic groups.
Age is the strongest risk factor for dementia. Prevalence increases sharply with age:
3% of adults aged 65–69 have dementia.
Rates rise to 35% among those aged 90 and older.
Race and Ethnicity:
Black or African American adults have the highest dementia prevalence (15%), followed by Hispanic/Latino adults (10%), and White adults (9%).
Black individuals also face the highest incidence rates, with 4.2% in 2015, decreasing to 3.1% by 2021.
Hispanic incidence declined from 3.7% to 2.6% over the same period.
White incidence decreased from 3.4% to 2.8% (this might be the real flaw in the study).
Despite declines, Black and Hispanic populations still have higher rates than White populations, though the gap has narrowed over time.
Education is a key factor: those with less than a high school education have a dementia prevalence of 13%, compared to 9% for those with a college degree or higher.
These disparities are linked to structural and social inequalities, including differences in access to healthcare, cardiovascular health, and lifelong socioeconomic conditions.
Sorry to hear that a strong intelligent voices (Alex B as well as J. Childers) can fall prey to propaganda (sole existence of JAMA, IMO).
Thx for your post and deep(er) perspective than others.
Very, very well said. I do wonder how many of those 45,000-85,000 observational studies did come from Harvard. I'm guessing a lot. If so, that would based a lot of the published observational nutrition research in the hands of one institution and base it on their tool, the FFQ, which may not be the best, but that's another post. IMHO.
Pause for a Simultaneous Sip
One of the challenges with studies like this isn’t the observational design itself — it’s how quickly modest associations get amplified into lifestyle prescriptions. Relative risk reductions become headlines, nuance disappears, and no one revisits the claim years later when outcomes don’t match expectations.
Some articles approve fantastic properties of coffee drinking.. others dissaprove intake and associate it with dementia & other ailments. I am a 76 yr old Cardiologist in general practice, and I consume 2 -3 cups of this brain energizer during the morning and sometimes on discussions with colleagues in the same coffee sharing. We are al around the same age. we are not pursuing to leave our most enjoyful drink in tne mornings, articles or no article... Respectfully. .
Dr. Mandrola,
In reference to your February 16 Sensible Medicine post, “Coffee is great but it does not prevent dementia,” I would like to offer a brief semantic and epistemological reflection.
First, a confession of origin: I come from a latitude where some claim the world’s most aromatic coffee is grown. I will nonetheless attempt intellectual sobriety.
Semantically, in epidemiology, few exposures “prevent” disease in an absolute sense. They modify probabilities. Thus, stating that coffee does not prevent dementia is technically correct if prevention implies total risk abolition. But the relevant question is whether moderate consumption reduces baseline risk—and by how much.
The study by Zhang et al. (2021), using UK Biobank data, reported non-linear associations between moderate coffee (and tea) intake and lower risk of stroke and dementia, with lowest risk around 2–3 cups daily. The authors claimed association, not causation. Their methodological caution was clear.
It is also true that long-term randomized controlled trials (RCTs) showing that coffee prevents incident dementia do not exist. But neither do such RCTs for walking every morning. Chronic disease epidemiology rarely allows decades-long molecularly isolated interventions with clinical endpoints.
Here lies the deeper issue.
Much research in cardiovascular disease and dementia has been framed within linear pathogenic models—lipid accumulation, metabolic overflow, amyloid deposition. RCTs inherit these ontologies. Randomization reduces allocation bias, but it does not correct the conceptual framing of disease as a single-pathway excess requiring molecular subtraction.
Chronic disease, however, is systemic, adaptive, and contextual.
Umbrella reviews by Poole et al. (2017) and Grosso et al. (2017) showed consistent inverse associations between moderate coffee consumption and all-cause mortality, cardiovascular disease, type 2 diabetes, liver disease, Parkinson’s disease, and depression—greatest around 3–4 cups daily. More recent syntheses (e.g., Gill et al., 2024; Ungvari et al., 2024) continue to report favorable associations with cardiometabolic health and plausible mechanisms involving insulin sensitivity, endothelial function, and inflammation—while acknowledging predominantly observational evidence.
Consistency and biological plausibility appear present; magnitude of independent causality remains debated.
Perhaps, however, the debate is misframed.
From a salutogenic perspective, the morning cup is not merely caffeine and polyphenols. It is a ritual embedded in circadian timing, social interaction, mood regulation, and behavioral organization. Dementia—particularly vascular and Alzheimer-type—shares substrates with cardiometabolic deterioration, chronic inflammation, endothelial dysfunction, and circadian disruption. In that broader system, coffee may act less as an isolated neuroprotective agent and more as a behavioral marker within a coherent metabolic ecology.
It is not the cup alone. It is the system in which the cup is embedded.
Rather than asking whether coffee prevents dementia, perhaps the better question is: within what biological and social metabolism do we place that daily cup? There—in the organization of the system—is where prevention may truly reside.
References
Echeverry-Raad, J. (2024). A falsehood that has been repeated many times becomes true: The origin of the diabesity pandemic, the most lethal of the 21st century? Journal of Diabetes, Metabolic Disorders & Control, 11(1), 39–50. https://doi.org/10.15406/jdmdc.2024.11.00276
Gill, D., et al. (2024). An umbrella review of meta-analyses to understand the effect of coffee consumption and the relationship between stroke, cardiovascular heart disease, and dementia. [Publication details pending].
Grosso, G., Godos, J., Galvano, F., & Giovannucci, E. L. (2017). Coffee, caffeine, and health outcomes: An umbrella review. Annual Review of Nutrition, 37, 131–156. https://doi.org/10.1146/annurev-nutr-071816-064941
Poole, R., Kennedy, O. J., Roderick, P., Fallowfield, J. A., Hayes, P. C., & Parkes, J. (2017). Coffee consumption and health: Umbrella review of meta-analyses of multiple health outcomes. BMJ, 359, j5024. https://doi.org/10.1136/bmj.j5024
Ungvari, Z., et al. (2024). Coffee consumption and cardiometabolic health. [Publication details pending].
Zhang, Y., Yang, H., Li, S., Li, W. D., & Wang, Y. (2021). Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLoS Medicine, 18(11), e1003830. https://doi.org/10.1371/journal.pmed.1003830
Mandrola nails the core problem here: an observational association is being marketed as a preventive intervention, and the confidence of the coverage is wildly out of proportion to what the design can support. 
A few things I’d underline as a physician-scientist:
1. Your Bayesian prior should be low. Dementia is a heterogeneous syndrome (vascular, neurodegenerative, inflammatory, toxic, genetic), so the idea that one exposure like coffee would cleanly “prevent dementia” should trigger skepticism before you even look at a p-value. 
2. Adjustment is not randomization. You can only adjust for what’s captured, and “coffee drinker” is a cluster label for countless health, socioeconomic, sleep, work-pattern, and behavioral differences that don’t fit neatly in a spreadsheet. 
3. Effect-size + subgroup results are a tell. When a simple habit shows an ~18% lower dementia risk overall and looks even “better” in age strata, that’s often the signature of residual confounding/selection effects rather than biology doing something magical. 4. Analytic flexibility is the quiet elephant. With enough plausible modeling choices, you can often “find” a publishable association, especially in nutrition/behavior epidemiology, without anyone committing fraud. 
Enjoy coffee if you enjoy coffee. But if we’re serious about dementia prevention, we should keep the spotlight on interventions with stronger causal footing (BP control, physical activity, sleep, hearing, metabolic risk, smoking, education/cognitive engagement), not another headline that confuses correlation with protection.
All good with doubting observational data. If only people would do it consistently (ahemmm...vaccines...). But the claimed effect here with coffee is entirely plausible. This is what happens when you go to medical school and don't understand pleiotropy of natural medicines and experience supplements as an alternate dimension. No offense, but it's true.
A reflexive negative reaction to observational studies is itself a cognitive bias.
Observational and epidemiological studies are perfectly good puzzle pieces. The fixation on blinded controlled studies is not helpful. Those are great too, and in some ways better. But they can never cover the same size population or duration. All forms of evidence are imperfect.
In this particular case, the protective effects of caffeine have been seen in multiple observational studies over the years, enough that it should not be ignored. If there were no mechanism explaining why this effect would work, it would be a little shaky (though still valid-though-imperfect evidence). But there is an excellent, well supported, mechanism.
Studies demonstrate that, in mice caffeine and Eicosanoyl-5-hydroxytryptamide (EHT), which is found in coffee beans work together to improve activity of the PP2A catalyst, which protects the brain against abnormal protein accumulation. Studies in mice showed that the combination of EHT and caffeine reduced neuroinflammation and protected against oxidative stress, and manifested in actual effects in behavior.
"But that's just mice, not people."
No. When you have an observational study, a very plausible mechanism, and demonstrated efficacy in mice, that adds up to solid evidence. Is it enough to approve a drug? Maybe not. But is it enough to make it reasonable for people to take it seriously? Yes.
"Good enough for drug approval" is not the same thing as "good enough to incorporate into your personal practices."
But just to be safe....I'll still keep drinking my coffee in the morning 🤣-
This will inevitably be used frequently on an individual level (not saying JAMA or authors are suggesting this) to justify unhealthy high calorie coffee consumption with abundantly added sugar and creamer.
Yes-posts such as these are exactly why I’m a subscriber! Thanks Dr. Mandrola.
i enjoyed ready this commentary with my morning cup of joe. felt smarter in 2 ways