Obesity in Midlife Increases Risk of Dementia and Alzheimer’s Disease

Nicolas Cherbuin PhD ARC Future Fellow - Director of the NeuroImaging and Brain Lab Centre for Research on Ageing, Health and Wellbeing Research School of Population Health - College of Medicine Biology and Environment Australian National UniversityMedicalResearch.com Interview with:
Nicolas Cherbuin PhD

ARC Future Fellow – Director of the NeuroImaging and Brain Lab
Centre for Research on Ageing, Health and Wellbeing
Research School of Population Health – College of Medicine Biology and Environment
Australian National University

Medical Research: What is the background for this study? What are the main findings?

Dr. Cherbuin: A number of modifiable risk factors for cognitive aging dementia and Alzheimer’s disease have been identified with a high level of confidence by combining evidence from animal research and systematic reviews of the literature in humans that summarise the available findings without focusing on extreme findings that come about from time to time in research. One such risk factor is obesity for which we have previously conducted a systematic review (Anstey et al. 2011). This showed that obesity is associated with a two-fold increased risk of dementia and a 60% increased risk of Alzheimer’s disease. What was surprising is that this effect was only detectable for obesity in middle age but not old age. This might suggest that the obesity only has an adverse effects on brain health earlier in life and that this effect fades at older ages. This is unlikely because a number of animal studies have shown that the biological mechanisms linking obesity with brain pathology do not disappear with older age but in fact appear to increase. Moreover, human studies show that thinking abilities decline faster in obese individuals. An alternative explanation is that human epidemiological studies investigating this question in older individuals include participants who do not have clinical dementia but in whom the disease is developing. Since dementia and Alzheimer’s disease pathology is associated with weight loss it is possible that estimated effects in humans have been confounded by this issue. Another possible confounder is that older people tend to lose muscle mass (sarcopenia) this may lead to the paradoxical condition in aging where a person has a normal weight but has excessive fat mass. Since it is fat tissue that is linked to risk to cerebral health it may have led to the apparently contradictory findings that obesity may not be a risk in older age. It is therefore of great interest to clarify whether obesity in early old age in individuals free of dementia is associated with poorer cerebral health. The hippocampus is one of the structures most sensitive stressors. Because obesity is known to lead to a state of chronic inflammation which is deleterious to the hippocampus, it was a logical structure to investigate. Moreover, the hippocampus is needed for memory function and mood regulation and is directly implicated in the dementia disease process.

This study investigated 420 participants in their early 60s taking part in a larger longitudinal study of aging taking place in Canberra, Australia and who underwent up to three brain scans over an 8-year follow-up. These individuals were free of dementia and other neurological disorders. Associations between obesity and shrinkage of the hippocampus were investigated with longitudinal analyses which controlled for major confounders.

The main findings were that overweight and obese participants had smaller volume of the hippocampus at the start of the study. In addition, the hippocampus shrunk more in these individuals over the follow-up period.

Medical Research: What should clinicians and patients take away from your report?

Dr. Cherbuin: Obesity is a significant risk factor for cerebral health and our findings suggest that these effects are not diminished in aging.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Cherbuin: Further research should be conducted to determine the extent to which obesity is associated with cognitive decline across the lifespan. The biological mechanisms underlying these effects should be investigated in details. Developing effective interventions to change behaviour, reduce energy intake, discourage consumption of processed and fast foods and soft drinks, and incite greater physical activity should be a priority.

Medical Research: Is the hippocampus shrinkage reversible? 

Dr. Cherbuin: At this stage it is not completely clear whether some shrinkage is reversible. The hippocampus is one of two brain regions where significant numbers of new neurons are produced. Given obesity is associated with a slowing of production of new neurons (neurogenesis) in animals it would be expected that weight loss would be associated with some recovery.

One animal study (Grayson et al. 2014) has shown that obese animals that were administered two types of gastric surgery performed similarly to control rats with normal weight on a caloric restriction diet whereas untreated obese rats performed significantly worse on a memory task. This suggests that at least recovery in function is possible in animals.

Medical Research: Based on your results, what advice would you give to those who are worried about cognitive decline? 

Dr. Cherbuin: We should all be concerned by cognitive decline. The way to decrease our anxiety about it is to lead healthier lives which includes eating better food (little or no fast food and no soft drinks, plenty of fish, little meat, and plenty of fruit and vegetables) in smaller quantities, keeping track of our weight and remaining in the healthy weight range (there is no biological reason to become heavier with age), exercise (2-3 times a week at medium/high intensities throughout life; walk or cycle to work; walk up the stairs, work standing when possible, etc), monitor health and seek health advice regarding chronic conditions, deal with mental health (there is a reciprocal ling between mood disorders, obesity, cardiometabolic disease and cerebral health and dementia).

Citation:

Neuroscience14 abstract:

Obesity and being overweight is associated with hippocampal atrophy: the path through life study

 

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