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Accelerated bio-cognitive aging in Down syndrome: State of the art and possible deceleration strategies.

ABSTRACT: Down syndrome (DS) has been proposed by George Martin as a segmental progeroid syndrome since 1978. In fact, DS persons suffer from several age-associated disorders much earlier than euploid persons. Furthermore, a series of recent studies have found that DS persons display elevated levels of age biomarkers, thus supporting the notion that DS is a progeroid trait. Nowadays, due to the progressive advancements in social inclusion processes and medical assistance, DS persons live much longer than in the past; therefore, the early-onset health problems of these persons are becoming an urgent and largely unmet social and medical burden. In particular, the most important ailment of DS persons is the accelerated cognitive decline that starts when they reach about 40 years of age. This decline can be at least in part counteracted by multi-systemic approaches including early-onset cognitive training, physical activity, and psychosocial assistance. However, no pharmacological treatment is approved to counteract this decline. According to the most advanced conceptualization of Geroscience, tackling the molecular mechanisms underpinning the aging process should be a smart/feasible strategy to combat and/or delay the great majority of age-related diseases, including cognitive decline. We think that a debate is needed urgently on if (and how) this strategy could be integrated in protocols to face DS-associated dementia and overall unhealthy aging. In particular we propose that, on the basis of data obtained in different clinical settings, metformin is a promising candidate that could be exploited to counteract cognitive decline in DS.

SUBMITTER: Franceschi C

PROVIDER: S-EPMC6516152 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Accelerated bio-cognitive aging in Down syndrome: State of the art and possible deceleration strategies.

Franceschi Claudio C Garagnani Paolo P Gensous Noémie N Bacalini Maria Giulia MG Conte Maria M Salvioli Stefano S

Aging cell 20190215 3

Down syndrome (DS) has been proposed by George Martin as a segmental progeroid syndrome since 1978. In fact, DS persons suffer from several age-associated disorders much earlier than euploid persons. Furthermore, a series of recent studies have found that DS persons display elevated levels of age biomarkers, thus supporting the notion that DS is a progeroid trait. Nowadays, due to the progressive advancements in social inclusion processes and medical assistance, DS persons live much longer than ...[more]

PMID: 30768754

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Project description:BackgroundAdvances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy.DesignThis review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI.ResultsEvidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens.ConclusionsCRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer.

Dataset Information

Accelerated bio-cognitive aging in Down syndrome: State of the art and possible deceleration strategies.

Publications

Accelerated bio-cognitive aging in Down syndrome: State of the art and possible deceleration strategies.

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