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Primary Care Corner with Geoffrey Modest MD: Sugary beverages and Alzheimer’s

4 May, 17 | by gmodest

​​​The second study from the Framingham Study Offspring cohort database found that increased intake of sugary sweet beverages was associated with lower total brain volume by MRI and poorer performance on neuropsychological testing (see ). For first study, see here


–4276 participants had neuropsychological testing and 3846 had brain MRI imaging

–mean age 54, 46% male, 21% high school degree/31% some college/46% college grads, systolic BP 121 mmHg/17% on BP treatment, total chol 194/HDL 57, 8% diabetes, 2% atrial fibrillation, 10% current smoker, waist-to-hip ratio 0.9 (the WHO defines abdominal obesity as >0.90 for men and >0.85 for women)

–total consumption of sugary beverages:

–< 1x/d in 56%

–1-2 x/d in 29%

–> 2x/d in 15%

–31% consumed fruit juice ≥​​ 1x/d

–diet soft drinks were consumed more regularly than sugar-sweetened ones:  49% no diet soft drinks, 35% up to 6/wk, 16% ≥​​ 1/d

–total calorie intake 1942 cal/d, but increased from 1782 in those consuming <1 sugary beverage/d, to 2007 if 1-2/d, to 2413 if >2/d; similarly, saturated fat increased from 22 to 24 to 27 g/d


–as compared to consuming <1 sugary beverage/day, higher intake was associated with:

–lower brain volume (more so if >2/d than1-2/d)

–poorer performance on memory tests: both immediate and delayed recall

–lower hippocampal volume, borderline significant [the hippocampus is the part of the brain that consolidates short-term information into long-term memory]

–daily fruit juice intake was associated with:

–lower total brain volume, hippocampal volume, and poorer immediate and delayed recall

— however, none of these associations reached statistical significance in the most highly adjusted model, which included not just age, sex, caloric intake, education, blood pressure, smoking, cardiovascular disease, or cholesterol, but also included saturated fat, trans fat, dietary fiber, and physical activity.

— Diet soft drinks had only a small effect on total brain volume and on poor performance on the test of similarities but not other memory tests.

— Essentially no difference in subclinical markers of vascular brain injury (silent brain infarcts and white-matter hyperintensity volume)


–11 million metric tons of sugar were consumed by Americans in 2016 (per the US Dept of Agriculture)

–a recent blog  highlighted the remarkable statistic that “on average 26.3% of US adults consume at least one sugar-sweetened beverage daily, up to 41.4% in Mississippi, the highest of states, and that soda by itself was consumed by 24.5% of those 18-34 yo, and 47.4% in Mississippi). And a NHANES study (Welsh JA. JAMA 2010; 303(15): 1490) found that on average, 15.8% of calories came from added sugars, and that >25% of the patients got >25% of their total energy from added sugar.”

— Interestingly, there was not much of an association between sugar intake and vascular brain injury, despite studies showing that sugar consumption is associated with cardiovascular disease. Instead the current study found a more profound association with several markers of preclinical Alzheimer’s disease. This is also found in mice, where sucrose intake is associated with increased tau phosphorylation, amyloid-beta aggregation, hippocampal atrophy, and reduced brain-derived neurotrophic factor, BDNF. In the Framingham study cohort, these researchers have found that one standard deviation increase in BDNF was associated with a 33% lower risk of Alzheimer’s disease, suggesting that BDNF might be a factor in mediating the association between dietary sugar and Alzheimer’s. Other studies have found that impaired glucose tolerance and chronically elevated blood glucose are associated with poor memory, perhaps related to changes in the hippocampal volume and microstructure

— as a clinical perspective, daily fruit juice intake was equivalent to 1.5 years of brain aging in terms of  total brain volume and 3.5 years of brain aging for the delayed memory scores. And, relative to no intake, consuming more than 3 sugar-sweetened soft drinks per week was associated with lower brain volume equivalent to 2.6 years of brain aging, and lower immediate memory recall equivalent to 13.0 years!!!

— this trial also highlights the potentially bad effects of fruit juice, noting that the general public underestimates the sugar content of fruit juice by an average of 48%, even though 100% fruit juice, without added sugar, contains lots of fructose with negligible fiber content

— see here which reviews the sordid (ie not so sweet) history of the sugar industry in promoting sugar and shifting the blame away from sugar in increasing heart disease, dental caries, etc, since the 1950s, despite lots of scientific evidence to the contrary
–and, a couple of more references on lifestyle and cognitive function:

— lower adherence to a Mediterranean diet has been associated with increased brain volume loss, supplementing other studies finding higher incidence of clinical dementia related to lifestyle issues, especially diet and exercise (see review)

​– a just published systematic review/meta-analysis of exercise interventions for cognitive function in adults older than 50, found that physical exercise improved cognitive function regardless of the cognitive status of the participants. This was true for both aerobic and resistance exercise of at least moderate intensity with the duration of 45 to 60 minutes per session, done on as many days of the week as feasible (see doi.10.1136/bjsports-2016-096587.)

so, these 2 articles (including the earlier one) confirm and extend the bad health effects of excess sugar and artificial sweeteners to include adverse effects on cognition and stroke. These studies are observational ones from the Framingham Heart Study, and therefore do not definitively confirm causality, but they do add to the growing literature on their adverse effects on the brain. And, in terms of lifestyle interventions, over the years I have found that it is much easier to help people stop sodas and juices, substituting water, than other dietary interventions.​ The low-hanging fructose….

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