The initial goal of ADNI was to recruit 800 adults, ages 55 to 90, to participate in the research – approximately 200 cognitively normal older individuals to be followed for 3 years, 400 people with MCI to be followed for 3 years and 200 people with early AD to be followed Axitinib VEGFR for 2 years.’ For up-to-date information, see [31].

Autopsy evaluations suggest that up to 78% of individuals with diagnosed alcoholism demonstrate some degree of brain pathology [8]. Neuroimaging and neuropathological evidence show prominent white matter loss (most notable in the prefrontal cortex, corpus callosum, and cerebellum) and neuronal loss in the superior frontal association cortex, hypothalamus, and cerebellum [1,9].

The frontal lobes of individuals with diagnosed alcoholism appear particularly susceptible to damage, with evidence of markedly decreased neuron density, volume shrinkage, and altered glucose metabolism and perfusion [10]. Partial recovery of white matter disturbances can occur with abstinence, and magnetic resonance imaging studies indicate early reversibility of white matter shrinkage that is accompanied by clinical improvement in cognitive and motor abilities [11,12]. The mechanism behind recovery from white matter damage is thought to involve the restoration of myelination and axonal integrity, but is vulnerable to repeated disruption if drinking is resumed [11]. Harper [1] concludes that the brain pathology of abusers of alcohol likely has two components: one of permanent change, the other transient.

While these findings reflect general structural changes in chronic abusers of alcohol, what lesions characterize a clinically identifiable dementia and the neuropathological process that underlies this process remain in dispute. The ‘neurotoxicity’ hypothesis suggests that the direct physiological effects of chronic alcohol exposure can cause neuronal loss through glutamate excitotoxicity, oxidative stress, and the disruption Drug_discovery of neurogenesis [13]. In particular, drinking patterns of repeated binges and withdrawal periods may enhance neuronal injury through increased vulnerability of upregulated N-methyl-D-asparate (NDMA) receptors to glutamate-induced excitotoxicity. Support for the neurotoxicity hypothesis emerges from animal studies, which have demonstrated dose-related ethanol-induced damage to brain structures – including the hippocampus, hypothalamus, and cerebellum – that correspond with impairments in memory and learning [14,15].

Cholinergic neurotransmission in the basal forebrain, which plays a key role in attention, these learning, and memory, also appears to be impacted by prolonged intake of alcohol. Imaging studies of ‘uncomplicated alcoholics’ – individuals with no history of nutritional deficiency, hepatic failure, or other indirect forms of brain injury – confirm structural abnormalities, including changes to the corpus callosum, pons, and cerebellum [12].