Alzheimer's Disease Education and Referral Center

Pioglitazone or Exercise to Treat Mild Cognitive Impairment

Pioglitazone or Exercise to Treat Mild Cognitive Impairment

Overall Status: 
Brief Description: 

The purpose of this study is to investigate novel treatments to delay progression to dementia in people with mild cognitive impairment (MCI) and metabolic syndrome (MS). The hypothesis is that treatment with pioglitazone or endurance exercise training will improve, stabilize, or attenuate decline in cognitive function compared to controls.

Patient Qualifications: 
Min AgeMax AgeGenderHealthy Volunteers
55 Years
Accepts Healthy Volunteers
Inclusion Criteria: 

  • More than age 55 years and community-dwelling
  • Able to perform a telephone interview
  • Able to speak, read, and understand English
  • Allow statin drug, angiotensin converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARB), non-steroidal anti-inflammatory drug (NSAID), or Vitamin E supplement but must be on a stable dose for at least 2 months
  • Women must be postmenopausal (no menses for 12 months or more)
  • Must meet three of the five requirements for Metabolic Syndrome: * Waist measurement: greater than 102 cm for men and 88 cm for women * Fasting hypertriglyceridemia: 150 mg/dl (1.7 mmol/L) or higher * Low HDL cholesterol: less than 40 mg/dl (1.0 mmol/L) for men and 50 mg/dl (1.3 mmol/L) for women * Hypertension: higher than 130 mmHg systolic or 85 mmHg diastolic (average of two seated measurements) or currently using an antihypertensive medication * Elevated (untreated) fasting glucose: 100 mg/dl (5.6 mmol/L) or higher
  • Meet the study's four-step screening process for MCI (to rule out dementia)

Exclusion Criteria: 

  • Diagnosis of diabetes mellitus (DM), defined as: fasting blood sugar of 126 or higher, a history of known DM, or treatment with any glucose-lowering medication
  • Current diagnosis of dementia (or MMSE score of less than 24) or a neurological comorbidity other than MCI that might affect cognition including: large vessel stroke, brain tumor, severe brain injury, multiple sclerosis, or Parkinson's disease
  • Current diagnosis of depression; major psychiatric conditions such as bipolar disorder, psychosis, schizophrenia, or alcoholism that could affect the ability to understand and/or cooperate with the protocol
  • Significant cerebral vascular disease
  • Modified Hachinski score greater than 4
  • Pregnant, lactating, or having childbearing potential
  • Concomitant medications with significant cholinergic or anticholinergic effects or adverse effects on cognition, including: antipsychotics, tricyclic antidepressants, anticonvulsants, sedative/hypnotics, anxiolytics, glucocorticoids (chronic or frequent intermittent), gingko biloba, NMDA receptor antagonists, cholinesterase inhibitors, strongly lipid soluble beta blockers (e.g., propranolol)
  • Hormone replacement therapy (male or female)
  • Visual/hearing impairment that would significantly impact the ability to undergo psychometric testing
  • Significant medical illness or organ failure including hepatic or renal failure, unstable cardiac disease, or life expectancy of less than 18 months
  • Exercise-limiting conditions including: neuromuscular, joint/bone, cardiovascular, peripheral vascular, cerebrovascular, or pulmonary disease; recent myocardial infarction, pulmonary embolus, significant aortic stenosis; exercise limiting obesity
  • Untreated B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowable)
  • Uncontrolled hypertension: over 160 mmHg systolic or 100 mmHg diastolic (stable treatment is allowable)
  • Endurance exercise training more than twice a week for 20 minutes (at a level that produces sweating) consistently during the last 6 months
  • Unstable weight in the last 6 months
  • Increased risk for Pio toxicity, including baseline liver dysfunction, hematocrit less than 33% men or 30% women, problematic edema, or congestive heart failure
  • Stage 5 renal impairment (GFR less than 15 or dialysis)
  • Participating in another clinical trial

Detailed Description: 

Recent evidence has linked metabolic syndrome (MS) with cognitive impairment and dementia, including Alzheimer's disease (AD). AD is often preceded by mild cognitive impairment (MCI), characterized by memory impairment but no functional impairment.The conversion rate from MCI to AD is about 15 percent per year, or 5 to 10 times that of cognitively normal individuals.

The mechanism(s) linking MS and cognitive impairment are not clear, although there is evidence that insulin resistance and inflammation play key roles. Thiazolidinediones (TZDs), medications approved for the treatment of Type 2 diabetes, reduce insulin resistance and have anti-inflammatory properties. A recent pilot study showed improvements in some areas of cognition in people with MCI or mild AD who were treated with the TZD rosiglitazone.

Endurance exercise training (EET) is an established treatment for MS and insulin resistance. There is also evidence that EET may improve cognitive function as well.

In this study, participants with both MS and MCI will be randomized to a 6-month intervention with treatment with pioglitazone, endurance exercise training, or a placebo and no exercise. The hypothesis is that treatment with pioglitazone or EET will improve cognitive function compared to controls, as evidenced by either improvement, stabilization, or lesser decline in performance on cognitive testing.

Map Marker CityStateZip CodeStatusPrimary Contact

Geolocation is 39.7503186, -104.8367063

Lead Sponsor: 
National Institute on Aging (NIA)
Collaborator Sponsor: 
Facility Investigators: 
Robert S. Schwartz, MD
Principal Investigator
University of Colorado, Denver
Study Contact: 
Erica Borresen, BS
Locations ID 
NCT00736996 (follow link to view full record on in new window)
Official Title: 
Pioglitazone and Exercise Effects on Older Adults with MCI and Metabolic Syndrome
Study Start Date: 
November 2008
Study End Date: 
August 2011
Disease Stage: