21 Apr 2017

You knew sugary drinks were bad for your waistline and blood sugar—now add your brain to the list. An April 20 paper in Stroke, from scientists led by Sudha Seshadri, Boston University School of Medicine, and Paul Jacques, Tufts University, Boston, reports that artificially sweetened drinks—and sugary ones to some degree—raise the risk for dementia and stroke. People who drank more than one diet soda per day had nearly three times the risk of people who did not. In addition, a March 6 paper in Alzheimer’s Disease and Dementia, also from Seshadri’s group, links sweet beverages to markers of preclinical AD. First author Matthew Pase found smaller brain volume and weaker episodic memory in middle-aged people who drank an excess of soda, fruit juice, even diet soda. The results suggest that letting that sweet tooth become a habit could undermine your long-term brain health.

“The two papers underscore the idea that sugary drinks are unhealthy, and that diet beverages are not an alternative,” Pase told Alzforum. “Our results point out that we need to better understand the effects of these beverages for not only the brain but for other aspects of health.” The new data strengthen the notion that sweet drinks are bad for you, agreed Christian Holscher, Lancaster University, U.K, who was not associated with the studies.

Connections between sugar and Alzheimer’s are not new. Previous studies tied too much sugar to Aβ aggregation, tau phosphorylation, and poor memory in mice (see Orr et al., 2014; Cao et al., 2007). Other work associated high sugar intake and chronically high blood sugar with memory problems in people (see Ye et al., 2011; Grabenhenrich and Roll, 2014). Diet sodas, too, with their artificial sweeteners, have been tied to vascular disease and stroke (Gardener et al., 2012;  Bernstein et al., 2012). However, it was unclear until now whether sugar- or artificially-sweetened beverages led to markers of preclinical decline or dementia in people.

To see if there was an association with markers of preclinical AD, Pase used data from the Framingham Heart Study. For the first paper, he looked at people enrolled in the Offspring and Third Generation cohorts, who are the children and grandchildren, respectively, of the original study participants. The 6,950 people in this group are now middle-aged, in their 50s on average. At one of their assessments, which take place every four years, they indicated on a dietary questionnaire how often they drank fruit juice, sugar-sweetened soda, or diet soda. On the same day, a subset of 4,276 completed neuropsychological tests of episodic memory and other aspects of cognitive function, and 3,846 underwent structural MRI scans to measure hippocampal and total brain volume.

The researchers found that hippocampi and whole brains were smaller in people who regularly sipped the sweet stuff. Compared to people who consumed none, those who drank between one and two beverages, or more than two per day, had brain volumes typical of someone 1.6 and 2.0 years older, respectively. Episodic memory fared even worse, with performances more like those of someone 5.8 and 11 years older, respectively. Even fruit juice—considered by some to be healthier—and diet beverages were associated with smaller brains and worse memory, though the effects were weaker.

The researchers had no data on AD-specific markers for this paper, but Pase told Alzforum that they are now collecting Aβ and tau PET scans in a subset of Framingham participants for future study. They also plan to analyze Aβ and tau in the blood.

To look for an association with stroke and dementia, which occur more often in aged populations, Pase focused on the Offspring Cohort. Based on the above results and previous studies, he wondered whether sweetened drinks were related to risk for dementia or stroke. He used data from 2,690 people who were older than 45 for stroke analysis, and from 1,395 people older than 60 for dementia analysis. Pase averaged drink preferences from food surveys taken over three assessments, then followed people for 10 years to see who developed either condition. In that decade, 97 people had strokes and 81 people developed dementia.

Diet drinks were overwhelmingly associated with both stroke and dementia, nearly tripling the risk of both in people who drank more than one per day, compared to those who drank none (see image below). Sugar-sweetened drinks had a weak, non-statistically significant association between dementia or stroke. This would seem to counter the findings in the Alzheimer’s and Dementia paper, which imply that sugary drinks set the stage for dementia. However, Pase pointed out that this study involved a smaller population who drank far more diet than sugar-sweetened drinks. “That might make it hard to detect associations between intake of sugary beverages and risk of dementia,” said Pase. He said other researchers might find positive associations in larger populations.

Soda Splits the Curves. People who steer clear of diet drinks (green) live longer without dementia than those who guzzle up to six per week (red) or more (blue).

Pase cautioned that these studies are based on self-report and under-represent minorities, and so may not generalize to the broader population. The research is also observational and cannot draw causal connections between sugar and Alzheimer’s. But it does point to a possible correlation.

What could be the mechanism? Pase noted that too much sugar can lead to diabetes and vascular disease, which in turn harm the brain, suggesting that cerebrovascular disease is a mediating factor. However, the link between sugary drinks and markers of preclinical AD is even stronger than that for vascular disease, wrote the authors, implying something else may be going on as well.

The finding on diet drinks is more of a puzzle, Pase told Alzforum. Artificial sweeteners have been tied to cardiovascular disease and stroke, so vascular mechanisms could once again be at play (Winkelmayer et al., 2005). Other studies suggest that diet drinks alter the stomach microbiota of mice and bring on glucose intolerance (Suez et al., 2014). 

Pase acknowledged the possibility that people with diabetes, who are at risk for dementia already, are drinking more diet soda to avoid sugar. Holscher agreed that diabetes could be a mediating factor. He noted that the Stroke paper adds evidence that insulin signaling—rather than excess glucose itself—is a main driver of dementia. People who drink diet beverages likely have lower glucose intake but dysregulated insulin, he said. Overall, both papers showed a clear correlation between both types of sweet drink and dementia, even if some of the results missed significance, Holscher told Alzforum.

The data bolster the case against sugar-sweetened beverages, potentially shoring up ongoing initiatives to tax sugary drinks across the United States, including in Philadelphia, San Francisco, the Navajo Nation, and Berkeley, California. More cities and states in the United States are considering such measures, as are countries around the world. The added cost is curbing public consumption, it seems. A study in the April 18 PLoS ONE reports that after one year, Berkeley’s tax on sugar-sweetened drinks reduced sales by nearly 10 percent, increased purchase of healthier beverages, and raised money for children’s nutrition and health programs (see Silver et al., 2017).—Gwyneth Dickey Zakaib

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References

Paper Citations

1. Orr ME, Salinas A, Buffenstein R, Oddo S. Mammalian target of rapamycin hyperactivity mediates the detrimental effects of a high sucrose diet on Alzheimer's disease pathology. Neurobiol Aging. 2014 Jun;35(6):1233-42. Epub 2013 Dec 14 PubMed.
2. Cao D, Lu H, Lewis TL, Li L. Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem. 2007 Dec 14;282(50):36275-82. PubMed.
3. Ye X, Gao X, Scott T, Tucker KL. Habitual sugar intake and cognitive function among middle-aged and older Puerto Ricans without diabetes. Br J Nutr. 2011 Nov;106(9):1423-32. Epub 2011 Jun 1 PubMed.
4. Grabenhenrich LB, Roll S. Higher glucose levels associated with lower memory and reduced hippocampal microstructure. Neurology. 2014 Jul 1;83(1):102. PubMed.
5. Gardener H, Rundek T, Markert M, Wright CB, Elkind MS, Sacco RL. Diet soft drink consumption is associated with an increased risk of vascular events in the Northern Manhattan Study. J Gen Intern Med. 2012 Sep;27(9):1120-6. Epub 2012 Jan 27 PubMed.
6. Bernstein AM, de Koning L, Flint AJ, Rexrode KM, Willett WC. Soda consumption and the risk of stroke in men and women. Am J Clin Nutr. 2012 May;95(5):1190-9. Epub 2012 Apr 4 PubMed.
7. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA. 2005 Nov 9;294(18):2330-5. PubMed.
8. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. Epub 2014 Sep 17 PubMed.
9. Silver LD, Ng SW, Ryan-Ibarra S, Taillie LS, Induni M, Miles DR, Poti JM, Popkin BM. Changes in prices, sales, consumer spending, and beverage consumption one year after a tax on sugar-sweetened beverages in Berkeley, California, US: A before-and-after study. PLoS Med. 2017 Apr;14(4):e1002283. Epub 2017 Apr 18 PubMed.

Further Reading

News

1. Do ApoE4 and Diabetes Conspire to Spur Cognitive Decline? 10 Mar 2017
2. Vascular Disease in 50s Begets Brain Amyloid in 70s 14 Apr 2017
3. Consensus Reached: Dieting Monkeys Survive Longer 27 Jan 2017
4. Brain Imaging Gets the Scoop on Eating Disorders in FTD 4 Mar 2016