The Impact of Type 2 Diabetes on Cognition

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1 The Impact of Type 2 Diabetes on Cognition Laura D. Baker, PhD Associate Professor of Medicine & Public Health Sciences Associate Director, Wake Forest Alzheimer s Disease Center Wake Forest School of Medicine, Winston Salem NC

2 Overview Diabetes and cognitive impairment what s the connection? The epidemic of insulin resistance new road to Alzheimer s disease? Can treating insulin resistance optimize healthy brain aging, prevent or treat Alzheimer s disease and other types of dementia?

3 Medical Conditions that Compromise Resilience in Aging Hypertension Diabetes Sleep Apnea High Cholesterol Chronic Obstructive Pulmonary Disease (COPD) Head Injury Liver Disease Kidney Disease Malnutrition Alcohol Abuse Vascular Disease Nicotine Chronic Stress Depression

4 Impact of Type 2 Diabetes Centers for Disease Control: 2017 Estimates 48% of adults 65 years and older have prediabetes, and only 14% are unaware that they have the condition

5 Diabetes & Risk of Cognitive Decline & Alzheimer s Disease Older adults (>55 yrs) with type 2 diabetes have a 65% increased risk of developing Alzheimer s disease (compared to those without diabetes) Adults with diabetes or prediabetes have lower scores on cognitive tests

6 Role of Insulin in a Healthy Brain Increases energy and blood flow in specific brain regions Increases levels of chemicals and connections used by brain cells to communicate Increases brain activity Protects against toxic amyloid accumulation Enhances memory at optimal levels

7 Effects of Insulin Resistance What happens when insulin can not function? Cells in body and brain no longer respond to normal amounts of insulin Causes = poor diet, physical inactivity, obesity, chronic stress or sleep disruption, genetic vulnerability Effects of insulin resistance Reduced effectiveness of insulin on brain energy and chemistry impacts brain cell communication Reduced insulin levels in the brain Increased levels of toxic amyloid protein and inflammation in the brain Impaired memory

8 Insulin Resistance Associated with AD Pattern of HYPO-metabolism in the Brain (using PET imaging) Prediabetes Baker et al, 2010 MCI AD Mosconi et al, 2008

9 Prevalence of Diabetes in Adults Age 18 Years and Older <4.5% 4.5% 5.9% 6.0% 7.4% 7.5% 8.9% >9.0% Prevalence of Death due to Alzheimer s Disease in 2010 (National Vital Statistics System, Mortality) CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at

10 Insulin and Alzheimer s Disease Many adults with AD have brain and/or body insulin resistance Insulin levels and effectiveness are reduced in AD [Craft et al 1998] Could treatments that boost insulin effectiveness help patients with AD?

11 Intranasal Insulin Delivery: A New Therapy for AD? Large trial of intranasal insulin with ~250 participants underway at 30 sites across the country Results expected later this year If successful, intranasal insulin may be used to treat Alzheimer s

12 One Cause of Insulin Resistance: Unhealthy Diet Pounds of sugar consumed per person per year Average number of calories consumed per person per day

13 Diet and Alzheimer s Risk Reduced calorie intake slows aging by improving insulin effectiveness, which has many consequences for aging Western Diet Reduced Calorie Diet Colman et al. Science, 2009

14 Diet and Risk of AD Bayer-Carter et al. JAMA Neurology, 2011 Compared effects of 1 month bad diet (high saturated fat & sugar) with same calorie good diet (low sat fat & sugar) on markers of AD (amyloid and inflammation) in the spinal fluid of healthy adults Good Bad Amyloid Good Bad Inflammation Good Bad Memory * Changes reversed after resuming normal diet

15 Another Cause of Insulin Resistance

16 Change in Occupational & Leisure Physical Activity: 1960 to 2010 Occupational Leisure Activity Church et al. 2011, Ladabaum et al. 2014

17 Exercise Benefits Brain Function in Normal & Pathological Aging Animal studies: ++ effects on brain structure & function (neurons, inflammation, vessels, stress response, AD pathology) Clinical studies: Building support for ++ effects on cognition in healthy older adults & in those with a mild memory impairment

18 Aerobic Exercise & Brain Function In healthy adults, brain volume increased with 6 months of aerobic exercise in Older Adults Blue = gray matter Orange = white matter Colcombe et al, 2006 Baker et al, in preparation

19 300 participants with MCI 14 sites across the U.S. NIA-funded national trial to test whether exercise is medicine for mild cognitive impairment STUDY DESIGN * More than 170 investigators and staff involved in trial conduct, includes 50 YMCA Trainers

20 Healthy Diet & Physical Activity Most Potent Ways to Increase Insulin Sensitivity & Reduce Risk of Diabetes. And Therefore Alzheimer s Disease???

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22 Summary Insulin resistance and associated conditions increase risk of: Age-related cognitive decline Alzheimer s disease and other forms of dementia Increasing prevalence of insulin-resistance in an aging population foreshadows impending dementia epidemic Normalizing metabolic function may offer an important approach to optimize brain health, and protect against Alzheimer s and other forms of dementia

23 Thank you Questions?