Neurobiological arguments for a pathogenic multifactorial disconnective model of cognitive disorders from Alzheimer's disease in elderly people.

Incidence of Alzheimer's disease (AD) in people over 75 years is much higher, and the progression of cognitive deficit become faster, leading to a decrease of quality of life for patients and their families. In this context, it is proposed a multifactorial pathogenic model of disconnected cognitive circuits, which is combined with genetic and vascular-cerebral vulnerability elements, allowing an aggressive progression of neurodegenerative factors, favoring onset of dementia. Data from research studies on animal model (rat) highlighted central role of cerebral cholinergic deficit (which is amplified by cerebral ischemia) on the background of apolipoprotein E4 (ApoE4) genotype, favoring multifactorial disconnected mechanisms, by excess of beta-amyloid (β-A) or increase of vascular dysfunction. Depressive disorder, social stress and traumatic brain injury are favoring the excess in production of β-A. Hippocampal structure disconnects the cognitive circuits, and from a neuropsychological point of view can be many patterns, which are correlated with neuroimaging (hippocampal atrophy, cerebral siderosis, white matter hyperintensity, ventriculomegaly) or biological (hyperhomocysteinemia) factors. Identifying the pathogenic model of multifactorial disconnectivity in the rapid evolution of cognitive deficit in patients with AD may create the premises for an early diagnosis and treatment, based on the biological, neuropsychological and clinical elements.