minocycline in patients with alzheimer's disease

Conditions: Mild Cognitive Impairment; Alzheimer's Disease

Summary: cognitively normal individuals, patients with mild cognitive impairment (mci) or alzheimer's disease (ad) will undergo clinical screening, neuropsychological tests, blood and urine analyses, quantitative magnetic resonance imaging (mri) and proton (1h ) and carbon 13 (13c) magnetic resonance spectroscopy (mrs). each individual will receive minocycline oral administration for 4 weeks initially, after which mri, mrs and neuropsychological results will be recorded. if no adverse side effects occur, subjects will continue minocycline administration for an additional 5 months.

in the course of on-going trials of novel mri procedures for neurological diagnosis, the investigators have established non-invasive biomarkers (note: biomarkers are objective laboratory tests used in, but not replacing clinical diagnostic criteria of any disease,in this case age-related dementia of the alzheimer type and its pre-clinical forms including mild cognitive impairment - mci) which significantly assist in the diagnosis of alzheimer's disease. mrs, rather like blood tests which are applied for screening and exclusion of medical disorders, provides a pattern of brain chemicals from which this and many other diagnoses have become available (see: magnetic resonance spectroscopy in neurological diagnosis: e.r danielsen and b.d. ross, marcel dekker new york, 1999). diagnosis of alzheimer's disease has hitherto been exclusively a clinical diagnosis, made on the basis of non-specific tests by the treating physician/neurologist. furthermore, treatments have been of limited efficacy so that the pressure for conclusive diagnosis or an objective characterization of disease progression (or better, regression) has not been a priority. this conservative approach to alzheimer's disease changed in 2010 with the report of national institutes of aging. first: the failures of treatment have been ascribed to introduction only in patients with advanced disease ("dementia"). second: a preliminary form of ad, known as pre-clinical or mild cognitive impairment, has been recognized, distinct from, and generally earlier in the disease course. third: a new set of diagnostic criteria, which include objective 'biomarkers', from cerebrospinal fluid, genetic and imaging analyzes, has been accepted by the expert panel. finally, clinical trials of existing and new drugs for alzheimer's disease are expected to yield better results if initiated earlier - in the pre-clinical phase - and the outcomes evaluated by the earlier changes in an approved panel of biomarkers.

Eligibility criteria:
inclusion criteria: * cognitively normal elderly subjects between the ages of 55-90 and patients aged 55 - 90 years who have mild cognitive impairment (mci) or clinically defined alzheimer's disease. exclusion criteria: * any person with medical devices such as cardiac pacemakers/defibrillators or neuro-implants as they are contra-indications for mri/mrs exam. * since the effects of mri are unknown to the fetus or unborn child, any person who is or may be pregnant will be excluded from the study. * history of known allergy or intolerance to minocycline or any other tetracycline * impaired renal function (plasma creatinine) or blood urea nitrogen (bun) levels exceeds twice normal upper limit which can result in higher serum levels of tetracycline, azotemia, hyperphosphatemia and acidosis.

Keywords: magnetic resonance imaging magnetic resonance spectroscopy neuroinflammation mild cognitive impairment alzheimer's disease minocycline