Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Abstract

IntroductionAlzheimer's disease (AD) is the leading cause of dementia in the elderly. Prevalence and incidence of this type of dementia is increasing and extensive research has focused on AD pathogenetic mechanisms to find effective preventive procedures and therapeutic drugs. However, no therapy is available. Therefore, focusing upon diverse aspects of the disease in order to discover new therapeutic strategies appears to be relevant for patients. Moreover, new approaches to the disease's pathogenesis may open innovative prevention opportunities for the elderly or other groups of people without manifest cognitive alterations, but with increased risk of developing dementia.Brain amyloid deposits and intra neuronal neurofibrillary tangles (NFTs) have been suggested as inducers of the disease [1,2]. However, these neuropathological alterations are often also present in the brain of elderly without cognitive alterations or AD pathology [3]. Therefore, it is uncertain whether amyloid or other proteinaceous brain depositions might be causatively linked to AD.The biological role of the amyloid precursor protein (APP) and its proteolytic derivatives (A-beta peptide) in normal brain is still uncertain [4]. However, recent data showed that A-beta peptide is an anti-microbial factor [5]. A recent study reported that the A-beta peptide showed an in vitro anti-virus activity [6]. Therefore, A-beta peptides may play multiple roles in human brain and contribute to antimicroorganism responses.As we elsewhere discussed, genetic data from four genome wide association (GWA) studies on AD [7][8][9] suggested that persistent virus infections may be potentially associated with the age related cognitive decline. In fact, this specific genetic signature may predispose to AD by affecting the individual susceptibility to virus infections [7] during the age associated decline of immune competence. Adults with Down's syndrome (DS) o trisomy of chromosome 21show an elevated risk of cognitive decline and dementia with advancing age. The over expression of the APP gene on the chromosome 21 may lead to an early amyloid deposition in DS brains and be a susceptibility factor for AD [10].Middle age people with DS also show increased tangle brain deposition, neuronal loss and neuro-inflammation along with cerebrovascular pathology [10]. All these factors might accelerate brain aging in DS. A dramatic increase in life expectancy, coupled with a significant reduction in early mortality, has led to a substantial increment in the number of DS subjects reaching old age. This demographic picture parallels increased incidence and prevalence of the age related degenerative diseases in persons with DS.Chronic inflammation is associated with the pathogenesis of most chronic degenerative diseases. In fact, a relevant inflammatory component is always associated with AD, autoimmune diseases, diabetes, atherosclerosis, sarcopenia and cancer. It is of interest that increased levels of circulating inflammatory mediators may be secondary to impaired cytokine resp...

Executive Functioning in Adults with Down Syndrome: Machine-Learning-Based Prediction of Inhibitory Capacity

“…Patterns of cognitive changes during aging in adults with DS are diverse [12,13] but most severely affect memory, language, visuoconstructional skills, executive functions, and motor praxis skills [14][15][16][17][18][19][20]. Furthermore, a greater predisposition to develop Alzheimer's disease (AD) [21][22][23][24] has been noted, with onset of dementia marked by declines in episodic memory, visuospatial organization, visuospatial memory, and executive functions [25]. Importantly, alteration in executive functions has been recognized as one of the first symptoms of AD in persons with DS.…”