Lipoic Acid and Omega-3 Fatty Acids for Alzheimer's Disease

Current pharmacological agents for AD have had no impact on disease prevalence and have had
limited effects on improving the clinical course of AD. The exponential rise in the
prevalence, incidence, and cost of care for AD make finding therapeutic agents that can
either prevent AD or delay disease progression an urgent health care need. Since
inflammation, lipid dysregulation, and insulin resistance have each been associated with AD
pathology, the combination of lipoic acid plus fish oil has the potential to maximize
therapeutic benefit by acting on all three mechanisms associated with disease pathology. Our
primary study aim is to evaluate the ability of lipoic acid plus omega-3 fatty acids to
delay cognitive and functional decline in people with AD. The investigators will also
evaluate the effect of lipoic acid plus omega-3 fatty acids on changes in serum and plasma
biomarkers over 18 months to determine which markers are associated with whole brain atrophy
(MRI volume changes) and clinical outcomes (ADAS-cog, ADL). The associations identified will
aid in the identification of specific biomarkers that may be used to evaluate treatment
effects in future clinical trials.

Eligibility Criteria:

- 55 years or older

- Probable AD by National Institute of Neurological and Communicative Disorders and
Stroke/Alzheimer's Disease and Related Disorders Association - NINCDS/ADRDA criteria

- MMSE between 15-26

- Caregiver/study partner that can accompany participant to all study visits

- Stable use of cholinesterase inhibitors and memantine permitted - doses must be
stable for 4 months prior to study enrollment

- Stable doses of over-the-counter antioxidants (e.g. vitamin E, ginkgo biloba) are
permitted - dose must be stable for 4 months prior to study enrollment

- Stable dose of lipid lowering medication - dose must be stable for 4 months prior to
study enrollment

- Geriatric Depression Scale (GDS) - Score of < 5

- General health status that will not interfere with the participant's ability to
complete the study.

- Screening laboratory values within normal limits or, if abnormal, deemed clinically
insignificant by the investigator

- Sufficient English language skills to complete all testing

Exclusion Criteria:

- Non-AD dementia

- Residence in nursing home facility at screening visit (residence in community
assisted living and long-term care facilities in which the participant still performs
majority of basic activities of daily living will not be an exclusion)

- History of clinically significant stroke (stroke with neurologic deficits > 6 months
after diagnosis)

- Health conditions such as cancer diagnosed < 5 years prior to enrollment (prostate
cancer gleason grade < 3 and non metastatic skin cancers are acceptable), liver
disease, history of ventricular fibrillation or ventricular tachycardia, major
psychiatric disorder, central nervous system diseases (e.g. brain tumor, seizure
disorder)

- Insulin dependent diabetes or uncontrolled diabetes (diabetes controlled on
medications other than insulin are acceptable)

- Hyperlipidemic (triglycerides >500 mg/dl, LDL > 160 mg/dl, total cholesterol >240
mg/dl). LDL levels between 160 mg/dl and 165 mg/dl will be reviewed by the PI and
included if judged to be safe.

- Fish intake of one 6 ounce serving > once a week less than 4 months prior to
enrollment

- Omega-3 fatty acid supplement intake (e.g. fish oil capsules, cod liver oil, or
flaxseed oil) less than 4 months prior to enrollment

- Lipoic Acid supplementation less than 1 month prior to enrollment

- Taking systemic corticosteroids, neuroleptics, antiparkinsonian agents, and narcotic
analgesics. Certain low dose antipsychotic use will be reviewed by the principle
investigator on a case-by-case basis and may be allowed if determined that dose is
not strong enough to affect performance on cognitive evaluations. Low dose sinemet
and dopamine agonist taken once a day for restless leg syndrome is not an exclusion.

- Contraindications to MRI.

- Enrollment in another study