Cognitive impairment in the elderly: the need for a comprehensive approach.

In the elderly, the spectrum of cognitive decline ranges from what can be classified as normal cognitive decline with aging or mild cognitive impairment to dementia. There are various factors associated with the risk of even mild cognitive impairment, including common chronic diseases, and lifestyle, environmental, and genetic factors. Diabetes mellitus is well known to increase the risk of macroand microvascular complications. Increased atherosclerosis a critical factor leading to vascular complications in patients with type 2 diabetes (T2DM). Metabolic derangements of T2DM include insulin resistance, hyperglycemia, and release of excess free fatty acids, and other metabolic abnormalities, which can damage the vascular wall, giving rise to endothelial dysfunction, platelet hyperactivity, oxidative stress, and low-grade inflammation [1]. Diabetes and obesity are among the modifiable risk factors for cognitive impairment in the elderly. Several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation have been identified in cognitive impairment. Products generated by chronic hyperglycemia and the receptor for advanced glycation end products (RAGE) provide crucial links between diabetes and cognitive decline. Other mechanisms linking diabetes and cognitive impairment include neuroinflammation, impaired neuronal plasticity, and other molecular mechanisms that link obesity, diabetes, and Alzheimer disease [2]. Moreover, there are some common biomarkers that are differentially expressed when compared with healthy controls both in patients with Alzheimer disease and in those with T2DM. These biomarkers might provide a useful way of screening T2DM patients to identify those at risk of developing Alzheimer disease [3]. In addition to T2DM, the elderly commonly develop dyslipidemia. Statins have been widely used to treat lipid abnormalities in this population with beneficial effects on the scores of the Mini-Mental State Exam scale in the short term (£12 months). Moreover, statins could slow the deterioration of neuropsychiatric status and significantly improve activities of daily living ability in patients with Alzheimer disease, but did not show any advantage in changing Alzheimer’s Disease Assessment Scale-cognitive scores [4]. A systematic review and meta-analysis of observational studies found no neurocognitive risk associated with statin treatment and suggests a potentially favorable role of statins in clinical settings [5]. In response to the Food and Drug Administration informational warnings about possible impairment of neurocognition associated with the use of statins, a systematic review of randomized trials suggests no adverse cognitive effects of statins, and recommended their use to reduce significant cardiovascular events [6]. At a cellular level, the effects of statins include impact on the cholesterol composition of the nerve and glial cell plasmalemma, neurotransmitter receptor mobilization, myelination, dendritic arborization of neurons, synaptic vesicle release, and cell viability [7]. Randomized clinical trials are required to explore this potential neuroprotective effect. In rodent models of Alzheimer disease, statins have been shown to have positive effects on amyloidosis [8]. Atorvastatin ameliorates behavioral measures of cognitive impairment, and downregulates Ab1–42 production and tau hyperphosphorylation in the hippocampus and prefrontal cortex of amyloid precursor protein/presenilin 1 transgenic mice [9]. Encouraging effects of vitamin D, chondroitin, atorvastatin, and antihypertensive drugs, and adverse effects of antidepressants and benzodiazepines, may be important in affecting the rate of conversion to mild cognitive impairment and warrant further exploration in long-term studies [10]. In this issue, Kukula and Günaydın [11] report that atorvastatin significantly attenuated a deficit in the learned behavioral