Elevated blood glucose impairs memory

A study published online in Neurology on October 23, 2013 sheds light on the possible mechanisms of dementia in persons with elevated blood glucose but without diabetes as discussed in the previous post. The hippocampus, located in the inner aspect of both temporal lobes, is the key brain structure for memory consolidation and storage.

The researchers “aimed to elucidate whether higher glycosylated hemoglobin (HbA1c) and glucose levels exert a negative impact on memory performance and hippocampal volume and microstructure in a cohort of healthy, older, nondiabetic individuals without dementia.”

Learning tests, blood levels of HbA1c, glucose, and insulin, and advanced (3-tesla) MRI scans were performed on 141 persons  (72 women & 69 men) with an average age of 63. Those with lower glucose and HbA1c levels had better learning and memory and a healthier hippocampi:

“Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. …Moreover, mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure.”

The authors concluded:

“Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, strategies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.”

Source:  Higher glucose levels associated with lower memory and reduced hippocampal microstructure 

Related Post:  Even mild elevations in blood sugar increase risk of dementia

High carbohydrate intake and cognitive impairment in the elderly

An issue of Neurosciences Update published in 2012 by the Mayo Clinic  contains a Research Highlight on the Association Between Macronutrient Intake and Risk of Dementia. The authors studied the 128-item food-frequency questionnaires of 937 cognitively normal elderly, 2oo of which later developed mild cognitive impairment (MCI) or dementia.

Findings showed that among the 937 participants who were cognitively normal at baseline, MCI or dementia developed in 200 and that the risk of either condition was increased in participants with dietary patterns showing a high percentage of carbohydrate intake and reduced in those with a high percentage of fat and protein intake. The authors concluded that a diet high in carbohydrates and low in fats and proteins may increase the risk of MCI or dementia in elderly persons (Roberts et al. J Alzheimer’s Dis. 2012;32[2]:329-39).

The research study, freely available online, does not lists the type of carbohydrates consumed by the participants.  From the food-frequency questionnaires, the authors

… computed the proportion of total daily energy derived from total carbohydrates (% carbohydrate), fat (% fat), and protein (% protein); from carbohydrate components (sugar, non-sugar carbohydrate, fiber); and fat components (polyunsaturated fatty acids [PUFA], monounsaturated fatty acids [MUFA], saturated fats [saturated fats], and trans-fatty acids), and ranked participants by quartiles of intake.

The researchers suggest several mechanisms for the impact of high carbohydrate intake on cognitive function in the elderly, among them:

High carbohydrate and sugar intake may adversely affect cognition through several mechanisms. Hyperglycemia and diabetes may contribute to increased formation of advanced glycation endproducts (AGE), upregulation of the soluble receptors for AGEs, and may generate oxidative stress which in turn, enhances AGE formation. AGEs and oxidative stress have also been associated with greater cognitive decline and with AD through effects on amyloid and tau metabolism.

The increased risk of MCI with lower intake of fats and proteins may involve non-energy related pathways. Fat and protein intake may be required for the integrity of neuronal membranes and fats for the integrity of the myelin sheaths in the brain.

Bottom Line: Don’t let your grandparents skip out on high quality sources of fat and protein.

Brain Health: Put down that puzzle and go for a walk

Today’s issue of Neurology includes a research study on the relationship between physical activity and brain protection during aging. The amount of self-reported physical activity in 638 persons was correlated to brain health as visualized on MRI. The brains of those with a greater amount of physical activity showed less brain aging as measured by less atrophy (shrinkage), less loss of grey and white brain matter, and fewer hits (tiny holes) in white matter. While these hits, called hyperintensities on MRI, are often viewed as a normal part of aging, they most likely have underlying causes such as hypertension or neuroinflammation. This study provides evidence that they are occur less frequently in people who are active.

Also, the commonly held belief that performing crossword puzzles keeps older people sharp was not supported in this study. As the BBC reports:

Exercise did not have to be strenuous - going for a walk several times a week sufficed, the journal Neurology says.

But giving the mind a workout by doing a tricky crossword had little impact.

The study found no real brain-size benefit from mentally challenging activities, such as reading a book, or other pastimes such as socialising with friends and family.

Take home: In the elderly, exercise beats puzzles for brain health.   

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Brain Health: Stay smart with exercise

John Oró, MD

The authors of a new report published in the Mayo Clinic Proceedings reviewed 1,600 articles on the role exercise in cognitive function and found 130 studies pertinent to the issue. According to Medscape Neurology, the lead author, neurologist J. Eric Ahlskog, MD, PhD, notes:

Normal aging is associated with brain shrinkage, and this appears to be primarily mediated by progressive loss of synapses and related neuronal connections (the 'neuropil').

Dr. Ahlskog summarized the findings: 

We concluded that you can make a very compelling argument for [aerobic] exercise as a disease-modifying strategy to prevent dementia and mild cognitive impairment, and for favorably modifying these processes once they have developed.

While the type and amount of exercise varied among the studies, to Dr. Ahlskog, the studies suggests increasing "the heart rate to about 60% of maximum" in several sessions for a total about 150 minutes each a week. Even though the literature on resistance training was "less extensive", Dr. Ahlskog noted it was also beneficial. Cyrus Raji, MD, PhD of the University of Pittsburgh, not a participant in the study, concurred: 

While the majority of the evidence shows that aerobic physical activity is the best type of physical activity for this purpose, resistance training with weights may also be helpful.

Dr. Raji's impression of the study:

This paper nicely summarizes all of the latest evidence showing how regular physical activity can promote better brain health with aging and reduce the risk of Alzheimer's disease.

Brain Health: Fish oil helps maintain brain volume

By Dr. John

The first signs of human consciousness were found in Blombos Cave, South Africa and date to 70 to 80 thousand years ago. It is probably no accident that the site is littered with evidence of seafood consumption. Indeed, significant inclusion of seafood and fish in the human diet may represent the final nutritional factor in development of the human mind. 

The typical American diet is profoundly different from that of our Paleolithic ancestors and is increasingly considered the root of many modern diseases.

In a new study reported by EurekAlert, researchers at Rhode Island Hospital's Alzheimer's Disease and Memory Disorders Center revealed older adults taking fish oil supplements preserved brain volume and had smaller cerebral ventricles (a healthy sign suggesting less brain atrophy). Lead investigator, Lori Daiello, PharmD, states:

"In the imaging analyses for the entire study population, we found a significant positive association between fish oil supplement use and average brain volumes in two critical areas utilized in memory and thinking (cerebral cortex and hippocampus), as well as smaller brain ventricular volumes compared to non-users at any given time in the study. In other words, fish oil use was associated with less brain shrinkage in patients taking these supplements during the ADNI study compared to those who didn't report using them."

This observational study is just one additional piece of evidence demonstrating our continued movement away from the original human diet comes at a price. In this case, a shrinking brain. 

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