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About 500,000 Canadians are living with Alzheimer’s disease or a related dementia. This number is expected to soar to 1.1 million within 25 years. To date, there is no definitive way for health care professionals to forecast the onset of dementia in a patient with memory complaints. However, new research provides a glimmer of hope.
As a geriatrician, I have been looking at walking speed and variability as a predictor of dementia’s progression and whether it is associated with physical changes in the brain.
The “Gait and Brain Study” is a longitudinal cohort study funded by the Canadian Institutes of Health Research (CIHR). It assessed up to 150 seniors with mild cognitive impairment (MCI) — a pre-dementia syndrome — in order to detect an early predictor of cognitive and mobility decline, and progression to dementia.
While walking has long been considered an automatic motor task, emerging evidence suggests cognitive function plays a key role in the control of walking, avoidance of obstacles, and maintenance of navigation.
Drs. Michael Borrie (middle) and Manuel Montero-Odasso (right) performing a gait assessment of the data about gait speed and variability. Courtesy of author.
In our recent research, my team asked people with mild cognitive impairment to walk on a specially-designed mat linked to a computer. The computer recorded the individual’s walking gait variability and speed. This information was then compared to their walking gait while simultaneously performing a demanding cognitive task, such as counting backwards or doing calculations while walking (“walking-while-talking”).
It was subsequently determined that some specific gait characteristics are associated with high variability, particularly during walking-while-talking. These gait abnormalities were more marked in MCI individuals with the worst episodic memory and with executive dysfunction revealing a motor signature of cognitive impairment.
If confirmed in subsequent studies, these gait changes can be an effective predictor of cognitive decline and may eventually help with earlier diagnoses of dementia.
Finding early dementia detection methods is vital. In the future, it is conceivable that we will be able to make diagnoses of Alzheimer’s disease and other dementias before people even have significant memory loss. We believe that gait, as a complex brain-motor task, provides a golden window of opportunity for researchers to see brain function. The high variability observed in people with mild cognitive impairment can be seen as a “gait arrhythmia,” predicting mobility decline, falls, and now, cognitive impairment. Our hope is to combine these methods with promising new medications to slow or halt the progression of mild cognitive impairment to dementia.
Image Credit: Elderly person walking CC0 via Pixabay
The idea of extending life expectancy by modifying diet originated in the mid-20th century when the effects of caloric restriction were found. It was first demonstrated on rats and then confirmed on other model organisms. Fasting activists like Paul Bragg or Roy Walford attempted to show in practice that caloric restriction also helps to prolong life in humans.
For a long time the crucial question in this research concerned finding a molecular mechanism that demonstrated how caloric restriction might promote longevity. The discovery of such a mechanism is possible with very simple organisms whose genetics were well understood and whose genes could be switched on or off. For example, the budding yeast, nematodes and fruit flies are windows into the complicated genetics of longevity. Several discoveries have been made in recent years, including resveratrol, sirtuins, insulin growth factor, methuselah gene, Indy mutation.
Capillary feeding assay, developed in the laboratory of Seymour Benzer at Caltech, which allows tracking of consumed food
The effects of caloric restriction may be more complex than anticipated. Protein-to-carbohydrate ratio has been shown to play a large role in diet response. Additionally, medical concerns about danger of refined sugar and fructose for health have gained recognition, typically relating to high-mortality diseases and disorders, such as diabetes, diabetic complications, and obesity.
Following an initial study of antioxidant system of the budding yeast, we turned our sights to biogerontological studies after the discovery of possible molecular mechanism of resveratrol action in yeast model. However, we quickly realized that the fruit fly (specifically Drosophila) is likely a better model because we could then also investigate behavioural outcome and food intake. How would caloric restriction and the amount of carbohydrates in the diet affect the longevity of fruit flies?
Food with a dye enables measurement of food intake
Analysis of faecal spots left by fruit flies allows life-long measurement of medium ingestion
We posed the question of whether the type of carbohydrate fed would affect mortality in fruit flies, including fructose, glucose, a plain mixture of the two, and sucrose (a disaccharide composed from monomers, fructose and glucose). We wanted to see whether fructose is a “poison” or “toxicant” as can be found in publications or popular lectures of Professor Robert Lustig.
We found, surprisingly, that flies fed on sucrose ceased to lay eggs after several weeks of adult life, and sucrose shortened their mean life span at all concentrations above 0.5% total carbohydrate. On the other hand, we found that fruit flies were quite well adapted for living on fructose. Furthermore, this effect was not observed for plain mixture of fructose and glucose.
Dietary response surface where concentrations of protein and carbohydrate ingested are put on X and Y axes, while Z is any physiological parameter which may depend on protein-to-carbohydrate ratio
The results were surprising because sucrose is routinely used in laboratory recipes of fly food. Lower fecundity on sucrose was also unexpected. However, we realized that the effects we had observed in the study would not lead us to immediate sugar denialism. The fly food used in the study was quite different from usual fly food, and in human context resembled likely a spicy marmalade diet.
Nonetheless, it is known that egg laying in Drosophila is promoted by dietary proteins (taken up mostly from yeasts). The diets of our flies contained a very small amount of protein, and yet this deficiency did not interfere with egg laying on monosaccharides while disaccharide sucrose caused dramatic loss in fecundity.
Is it possible to apply our current data to human physiology? It seems to be rather difficult to build assumptions on healthy diet of humans based on the data obtained for insects. The insect physiology with their specific development hormones, probably different metabolism and metabolic demands stands far away from that of humans. Nevertheless, the general message is that the influence of diet on ageing cannot be reduced to simply amount of calories, or macronutrient balance. The quality of nutrients, the micronutrients, the peculiarities of digestion, including gut microbiota, should also be taken into account. While scientists are often forced to simplify models, to gain a better understanding of molecular, biochemical, genetic, and physiological grounds of ageing, our understanding would likely benefit from bringing a variety of researchers, from ecologists and mathematicians, into the discussion.
The Journals of Gerontology® were the first journals on aging published in the United States. The tradition of excellence in these peer-reviewed scientific journals, established in 1946, continues today. The Journals of Gerontology, Series A® publishes within its covers The Journal of Gerontology: Biological Sciences and The Journal of Gerontology: Medical Sciences.
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Image credit: All images courtesy of the authors. Do not use without permission.
