Chapter 42.Agents for Cognitive Disorders

Disruption of cholinergic neurotransmission and excitatory amino acids is correlated with the development of cognitive impairment and, specifically, Alzheimer’s disease (Mesulam 2004). Multiple mechanisms exist that may account for the progression of cognitive impairment, including those related to cholinesterase, N-methyl-d-aspartate (NMDA), vascular disease, defective neurogenesis, and oxidative damage (Aisen and Davis 1994; Bartus et al. 1982; Behl 1999; Behl et al. 1992; Crews and Masliah 2010; Jick et al. 2000; Kalaria et al. 1996; Liu et al. 2015; Selkoe 2000; Terry and Buccafusco 2003; Wolozin et al. 2000). An outcome of the disruption of many neurotransmitter systems, cognitive impairment may occur at any time during the disease process as synaptic plasticity becomes impaired, degrading the efficiency of neuronal transmission (Malik et al. 2007). It is intuitive that the earliest intervention prior to irreversible disease progression is optimal. Currently, it is unknown when the irreversible disease processes begin. The identification of specific markers that can guide clinicians in the initiation of prophylactic or abortive treatment prior to the development of cognitive or behavioral manifestations is highly desired. Continuing studies of circulating microRNAs in the cerebrospinal fluid and blood serum show promise as reliable biomarkers for early diagnosis of Alzheimer’s disease (Kim et al. 2014). For earl-onset autosomal dominant Alzheimer’s disease, mutations in presenilin 1, presenilin 2, and amyloid precursor protein are known (Kim et al. 2014).