Metabolic and endocrine factors in mild cognitive impairment.

Mild cognitive impairment (MCI) is a heterogeneous condition with cognitive changes between normal aging and dementia. Some forms of MCI are regarded as potential preclinical forms of dementia. The control of treatable somatic risk factors is of great relevance in patients with MCI, particularly as there is insufficient evidence for the efficacy of interventions targeting neurodegenerative processes, as used in manifest dementia. The etiology of MCI is varied including cerebrovascular risk factors and is also associated with metabolic and endocrine factors. Chronic kidney disease is a newly identified and independent risk factor for MCI. Testosterone substitution is useful if a low testosterone level is present but general screening for testosterone deficiency is not yet recommended. A relationship between MCI and vitamin D or subclinical thyroid dysfunction may exist, but the value of substitution is doubtful and requires large randomized placebo-controlled trials. Although an association between vitamin B12 deficiency or hyperhomocysteinemia and MCI is present, substitution of vitamin B12 or folate does not appear to prevent cognitive decline. Estrogen-only hormone replacement therapy may be considered only in younger postmenopausal women, but may have detrimental effects on cognitive function in older postmenopausal women. Other less familiar or unknown risk factors contributing to cognitive dysfunction should be identified as they are a potential target of prevention or intervention of MCI or dementia.