Publications by authors named "Carlo Custodero"

16 Publications

  • Page 1 of 1

The multidimensional prognostic index (MPI) for the prognostic stratification of older inpatients with COVID-19: A multicenter prospective observational cohort study.

Arch Gerontol Geriatr 2021 Apr 5;95:104415. Epub 2021 Apr 5.

Department of Primary Care, District 3, ULSS 3, Venice, Italy,; Department of Internal Medicine and Geriatrics, University of Palermo, Italy. Electronic address:

Background: The topic of prognosis in COVID-19 research may be important in adopting appropriate clinical decisions. Multidimensional prognostic index (MPI) is a frailty assessment tool widely used for stratifying prognosis in older people, but data regarding inpatients, affected by COVID-19, are not available.

Objectives: To evaluate whether MPI can predict in-hospital mortality and the admission to intensive care unit (ICU) in older inpatients hospitalized for COVID-19 infection.

Methods: In this longitudinal, Italian, multi-center study, older patients with COVID-19 were included. MPI was calculated using eight different domains typical of comprehensive geriatric assessment and categorized in three groups (MPI 1 ≤ 0.33, MPI 2 0.34-0.66, MPI 3 > 0.66). A multivariable Cox's regression analysis was used reporting the results as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: 227 older patients hospitalized for SARS-CoV-2 infection were enrolled (mean age: 80.5 years, 59% females). Inpatients in the MPI 3 were subjected less frequently than those in the MPI 1 to non-invasive ventilation (NIV). In the multivariable analysis, people in MPI 3 experienced a higher risk of in hospital mortality (HR = 6.30, 95%CI: 1.44-27.61), compared to MPI 1. The accuracy of MPI in predicting in hospital mortality was good (Area Under the Curve (AUC) = 0.76, 95%CI: 0.68-0.83). People in MPI 3 experienced a significant longer length of stay (LOS) in hospital compared to other participants. No association between MPI and ICU admission was found.

Conclusions: Frailty- as assessed by high MPI score - was associated with a significant higher risk of in-hospital mortality, longer LOS, and lower use NIV, whilst the association with ICU admission was not significant. These findings suggest that prognostic stratification by using the MPI could be useful in clinical decision making in older inpatients affected by COVID-19.
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http://dx.doi.org/10.1016/j.archger.2021.104415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020604PMC
April 2021

Multidimensional prognostic index (MPI) predicts non-invasive ventilation failure in older adults with acute respiratory failure.

Arch Gerontol Geriatr 2021 May-Jun;94:104327. Epub 2020 Dec 24.

Department of Interdisciplinary Medicine, University of Bari, Italy; Department of Geriatric Care, Orthogeriatrics and Rehabilitation, E.O. Galliera Hospital, Genova, Italy. Electronic address:

Background: Acute respiratory failure (ARF) is a very common complication among hospitalized older adults. Non-invasive ventilation (NIV) may avoid admission to intensive care units, intubation and their related complication, but still lacks specific indications in older adults. Multidimensional Prognostic Index (MPI) based on comprehensive geriatric assessment (CGA) could have a role in defining the short-term prognosis and the best candidates for NIV among older adults with ARF.

Methods: This is a retrospective observational study which enrolled patients older than 70 years, consecutively admitted to an acute geriatric unit with ARF. A standardized CGA was used to calculate the MPI at admission. Multivariate Cox regression models were used to test if MPI score could predict in-hospital mortality and NIV failure. Receiver operator curve (ROC) analysis was used to identify the discriminatory power of MPI for NIV failure.

Results: We enrolled 231 patients (88.2 ± 5.9 years, 47% females). Mean MPI at admission was 0.76±0.16. In-hospital mortality rate was 33.8%, with similar incidence in patients treated with and without NIV. Among NIV users (26.4%), NIV failure occurred in 39.3%. Higher MPI scores at admission significantly predicted in-hospital mortality (β=4.46, p<0.0001) among patients with ARF and NIV failure (β=7.82, p = 0.001) among NIV users. MPI showed good discriminatory power for NIV failure (area under the curve: 0.72, 95% CI: 0.58-0.85, p<0.001) with optimal cut-off at MPI value of 0.84.

Conclusions: MPI at admission might be a useful tool to early detect patients more at risk of in-hospital death and NIV failure among older adults with ARF.
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http://dx.doi.org/10.1016/j.archger.2020.104327DOI Listing
December 2020

Vascular dysfunction as a potential culprit of sarcopenia.

Exp Gerontol 2021 Mar 26;145:111220. Epub 2020 Dec 26.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA. Electronic address:

Aging-related changes to biological structures such as cardiovascular and musculoskeletal systems contribute to the development of comorbid conditions including cardiovascular disease and frailty, and ultimately lead to premature death. Although, frail older adults often demonstrate both cardiovascular and musculoskeletal comorbidities, the etiology of sarcopenia, and especially the contribution of cardiovascular aging is unclear. Aging-related vascular calcification is prevalent in older adults and is a known risk factor for cardiovascular disease and death. The effect vascular calcification has on function during aging is not well understood. Emerging findings suggest vascular calcification can impact skeletal muscle perfusion, negatively affecting nutrient and oxygen delivery to skeletal muscle, ultimately accelerating muscle loss and functional decline. The present review summarizes existing evidence on the biological mechanisms linking vascular calcification with sarcopenia during aging.
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http://dx.doi.org/10.1016/j.exger.2020.111220DOI Listing
March 2021

Translational insight into prothrombotic state and hypercoagulation in nonalcoholic fatty liver disease.

Thromb Res 2021 02 11;198:139-150. Epub 2020 Dec 11.

Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124 Bari, Italy. Electronic address:

Non-alcoholic fatty liver disease (NAFLD) is an emerging and threatening pathological condition, ranging from fatty liver (FL) to chronic steatohepatitis (NASH), liver cirrhosis, and eventually to hepatocellular carcinoma (HCC). Recent findings suggest that patients with NAFLD have a higher risk of cardiovascular events and thromboembolism and that this risk is independent of metabolic diseases that are frequently associated with NAFLD, such as diabetes, hyperlipidaemia, and obesity. The vascular involvement of NAFLD might be considered its systemic burden, conditioning higher mortality in patients affected by the disease. These clinical findings suggested the existence of a prothrombotic state in NAFLD, which is partially unexplored and whose underlying mechanisms are to date not completely understood. Here, we review the mechanisms involved in the pathogenesis of the prothrombotic state in NAFLD across the progression from the healthy liver through the different stages of the disease. We focused on the possible role of several metabolic features of NAFLD possibly leading to hypercoagulation other than endothelial and platelet activation, such as insulin-resistance, nitric oxide production regulation, and gut microbiota homeostasis. Also, we analysed the involvement of plasminogen activator inhibitor-1 (PAI-1) and thromboinflammation taking place in NAFLD. Finally, we described factors striking a prothrombotic imbalance in NASH cirrhosis, with a particular focus on the pathogenesis of portal vein thrombosis.
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http://dx.doi.org/10.1016/j.thromres.2020.12.002DOI Listing
February 2021

Liver fibrosis score, physical frailty, and the risk of dementia in older adults: The Italian Longitudinal Study on Aging.

Alzheimers Dement (N Y) 2020 24;6(1):e12065. Epub 2020 Aug 24.

Clinica Medica "Frugoni" and Geriatric Medicine-Memory Unit University of Bari Aldo Moro Bari Italy.

Introduction: Liver fibrosis increases progressively with aging and has been associated with poorer cognitive performance in middle-aged and older adults. We investigated the relationships between a non-invasive score for advanced liver fibrosis (non-alcoholic fatty liver disease [NAFLD] fibrosis score [NFS]) and dementia risk. We also assessed physical frailty, a common geriatric condition which is associated to dementia. We tested the joint effects of physical frailty and fibrosis on dementia incidence.

Methods: A total of 1061 older adults (65 to 84 years), from the Italian Longitudinal Study on Aging, were prospectively evaluated for the risk of dementia in a period between 1992 and 2001. Liver fibrosis was defined according to the NFS. Physical frailty was assessed according to the Fried's criteria. Cox proportional hazards models were used to estimate the short- and long-term risk of overall dementia, associated to the NFS, testing the effect modifier of physical frailty status.

Results: Older adults with only high NFS (F3-F4) did not exhibit a significant increased risk of overall dementia. Over 8 years of follow-up, frail older adults with high NFS had an increased risk of overall dementia (hazard ratio [HR]: 4.23; 95% confidence interval [CI]: 1.22 to 14.70,  = .023). Finally, physically frail older adults with low albumin serum levels (albumin < 4.3 g/dL) and with advanced liver fibrosis (F3-F4 NFS) compared to those with lower liver fibrosis score (F0-F2 NFS) were more likely to have a higher risk of overall dementia in a long term-period (HR: 16.42; 95% CI: 1.44 to 187.67,  = .024).

Discussion: Advanced liver fibrosis (F3-F4 NFS) could be a long-term predictor for overall dementia in people with physical frailty. These findings should encourage a typical geriatric, multidisciplinary assessment which accounts also for the possible co-presence of frail condition in older adults with chronic liver disease and liver fibrosis.
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http://dx.doi.org/10.1002/trc2.12065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443742PMC
August 2020

The relationship between interleukin-6 levels and physical performance in mobility-limited older adults with chronic low-grade inflammation: The ENRGISE Pilot study.

Arch Gerontol Geriatr 2020 Sep - Oct;90:104131. Epub 2020 May 30.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, United States. Electronic address:

Previous studies have found an inverse relation between serum concentrations of interleukin (IL)-6 and physical performance in seniors, however this was limited to higher functioning older adults with low to moderate levels of inflammation. We explored the consistency of this association in a cohort of mobility limited older adults with chronic low-grade inflammation. This study included 289 participants (≥ 70 years old) with IL-6 level between 2.5 and 30 pg/mL and a walking speed < 1.0 m/sec from the ENRGISE Pilot study. Physical performance was assessed using the short physical performance battery (SPPB), usual gait speed over 400 m, grip strength, and knee extensor and flexor strength measured by isokinetic dynamometry at 60 and 180°/sec. There was a significant inverse correlation between log IL-6 and knee extensor strength at 60°/sec (r= -0.20, p = 0.002), at 180°/sec (r = -0.14, p = 0.037), and knee flexor strength at 60°/sec (r = -0.15, p = 0.021). After adjustment for potential confounders, the values of knee extensor strength at 60°/sec showed a trend toward a progressive reduction across IL-6 tertiles as IL-6 levels increased (p = 0.024). No significant association was found between IL-6 and other objectively measured physical performance. The findings were generally of smaller magnitude and less consistent than previously reported, which suggests that the associations are attenuated in those with both elevated inflammation and mobility limitations. These results have implications for planning and interpreting future intervention studies in older adults with low-grade inflammation and mobility limitations.
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http://dx.doi.org/10.1016/j.archger.2020.104131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434645PMC
December 2020

Nicotinamide riboside-A missing piece in the puzzle of exercise therapy for older adults?

Exp Gerontol 2020 08 22;137:110972. Epub 2020 May 22.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA.. Electronic address:

Maintaining physical mobility is important for preventing age-related comorbidities in older adults. Endurance and resistance training prevent mobility loss in aging, but exercise alone does not always achieve the expected improvements in physical and cardiopulmonary function. Recent preclinical evidence suggests that a reason for the variability in exercise training responses may be the age-related dysregulation of the nicotinamide adenine dinucleotide (NAD+) metabolome. NAD+ is an essential enzymatic cofactor in energetic and signaling pathways. Endogenous NAD+ pool is lower in several chronic and degenerative diseases (e.g., cardiovascular diseases, Alzheimer's and Parkinson's diseases, muscular dystrophies), and also in aging. Exercise requires a higher energy expenditure than a resting state, thus a state of NAD+ insufficiency with reduced energy metabolism, could result in an inadequate exercise response. Recently, the NAD+ precursor nicotinamide riboside (NR), a vitamin B3 derivate, showed an ability to improve NAD+ metabolome homeostasis, restoring energy metabolism and cellular function in various organs in animals. NR has also been tested in older humans and is considered safe, but the effects of NR supplementation alone on physical performance are unclear. The purpose of this review is to examine the preclinical and clinical evidence on the effect of NR supplementation strategies alone and in combination with physical activity on mobility and skeletal muscle and cardiovascular function.
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http://dx.doi.org/10.1016/j.exger.2020.110972DOI Listing
August 2020

A multidimensional approach to frailty in older people.

Ageing Res Rev 2020 07 21;60:101047. Epub 2020 Mar 21.

National Institute on Aging, NIH, Baltimore, MD, United States.

Frailty is an important factor determining a higher risk of adverse health outcomes in older adults. Although scientific community in the last two decades put a lot of effort for its definition, to date no consensus was reached on its assessment. The mainstream thinking describes frailty as a loss of physical functions or as accumulation of multiple deficits. Recently, a novel conceptual model of frailty has emerged based on the loss of harmonic interaction between multiple domains (also referred as dimensions) including genetic, biological, functional, cognitive, psychological and socio-economic domain that ultimately lead to homeostatic instability. Therefore, the multidimensional aspects of frailty condition could be captured by the comprehensive geriatric assessment (CGA) and its derived Multidimensional Prognostic Index (MPI). This instrument has been applied in different clinical settings and in several cohorts of older adults with specific acute and chronic diseases, showing always excellent accuracy in stratifying population according the mortality risk and other negative health outcomes, i.e. hospitalization, institutionalization or admission to homecare services. This MPI "plasticity" provides a single numerical prognostic index which could be helpful in clinical decision making for the management of frail older adults.
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http://dx.doi.org/10.1016/j.arr.2020.101047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461697PMC
July 2020

Corrigendum to "Nutritional interventions and cognitive-related outcomes in patients with late-life cognitive disorders: A systematic review" Neurosci. Biobehav. Rev. 95 (2018) 480-498.

Neurosci Biobehav Rev 2020 Jan 5;108:889. Epub 2019 Dec 5.

Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Geriatric Unit & Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia, Italy; Department of Clinical Research in Neurology, University of Bari Aldo Moro, "Pia Fondazione Cardinale G. Panico", Tricase, Lecce, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.neubiorev.2019.11.022DOI Listing
January 2020

Biopsychosocial frailty and the risk of incident dementia: The Italian longitudinal study on aging.

Alzheimers Dement 2019 08 2;15(8):1019-1028. Epub 2019 Jul 2.

Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy; National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy; Geriatric Unit, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia, Italy. Electronic address:

Introduction: Frailty is a critical intermediate status of the aging process including physical, cognitive, and psychosocial domains/phenotypes. We operationalized a new biopsychosocial frailty (BF) construct, estimating its impact on the risk of incident dementia and its subtypes.

Methods: In 2171 older individuals from the population-based Italian Longitudinal Study on Aging (ILSA), we identified by latent class procedures the BF construct as the physical frail status plus at least one of the two items of the 30-item Geriatric Depression Scale impaired (items 3/10).

Results: Over a 3.5-year follow-up, participants with BF showed an increased risk of overall dementia (hazard ratio [HR]: 2.16, 95% confidence interval [CI]:1.07-4.37), particularly vascular dementia (VaD) (HR: 3.21, 95% CI: 1.05-9.75). Similarly, over a 7-year follow-up, an increased risk of overall dementia (HR: 1.84, 95% CI: 1.06-3.20), particularly VaD (HR: 2.53, 95% CI: 1.08-5.91), was also observed.

Discussion: In a large cohort of Italian older individuals without cognitive impairment at baseline, a BF model was a short- and long-term predictor of overall dementia, particularly VaD.
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http://dx.doi.org/10.1016/j.jalz.2019.04.013DOI Listing
August 2019

Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors.

Crit Care 2019 06 24;23(1):230. Epub 2019 Jun 24.

Department of Aging and Geriatric Research, University of Florida, 2004 Mowry Road, Gainesville, FL, 32611, USA.

Background: Sepsis survivors often develop chronic critical illness (CCI) and demonstrate the persistent inflammation, immunosuppression, and catabolism syndrome predisposing them to long-term functional limitations and higher mortality. There is a need to identify biomarkers that can predict long-term worsening of physical function to be able to act early and prevent mobility loss. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-accepted biomarker of cardiac overload, but it has also been shown to be associated with long-term physical function decline. We explored whether NT-proBNP blood levels in the acute phase of sepsis are associated with physical function and muscle strength impairment at 6 and 12 months after sepsis onset.

Methods: This is a retrospective analysis conducted in 196 sepsis patients (aged 18-86 years old) as part of the University of Florida (UF) Sepsis and Critical Illness Research Center (SCIRC) who consented to participate in the 12-month follow-up study. NT-proBNP was measured at 24 h after sepsis onset. Patients were followed to determine physical function by short physical performance battery (SPPB) test score (scale 0 to12-higher score corresponds with better physical function) and upper limb muscle strength by hand grip strength test (kilograms) at 6 and 12 months. We used a multivariate linear regression model to test an association between NT-proBNP levels, SPPB, and hand grip strength scores. Missing follow-up data or absence due to death was accounted for by using inverse probability weighting based on concurrent health performance status scores. Statistical significance was set at p ≤ 0.05.

Results: After adjusting for covariates (age, gender, race, Charlson comorbidity index, APACHE II score, and presence of CCI condition), higher levels of NT-proBNP at 24 h after sepsis onset were associated with lower SPPB scores at 12 months (p < 0.05) and lower hand grip strength at 6-month (p < 0.001) and 12-month follow-up (p < 0.05).

Conclusions: NT-proBNP levels during the acute phase of sepsis may be a useful indicator of higher risk of long-term impairments in physical function and muscle strength in sepsis survivors.
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http://dx.doi.org/10.1186/s13054-019-2505-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589880PMC
June 2019

Circadian rhythms: a possible new player in non-alcoholic fatty liver disease pathophysiology.

J Mol Med (Berl) 2019 06 5;97(6):741-759. Epub 2019 Apr 5.

Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124, Bari, Italy.

Over the last decades, a better knowledge of the molecular machinery supervising the regulation of circadian clocks has been achieved, and numerous findings have helped in unravelling the outstanding significance of the molecular clock for the proper regulation of our physiologic and metabolic homeostasis. Non-alcoholic fatty liver disease (NAFLD) is currently considered as one of the emerging liver pathologies in the Western countries due to the modification of eating habits and lifestyle. Although NAFLD is considered a pretty benign condition, it can progress towards non-alcoholic steatohepatitis (NASH) and eventually hepatocellular carcinoma (HCC). The pathogenic mechanisms involved in NAFLD development are complex, since this disease is a multifactorial condition. Major metabolic deregulations along with a genetic background are believed to take part in this process. In this light, the aim of this review is to give a comprehensive description of how our circadian machinery is regulated and to describe to what extent our internal clock is involved in the regulation of hormonal and metabolic homeostasis, and by extension in the development and progression of NAFLD/NASH and eventually in the onset of HCC.
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http://dx.doi.org/10.1007/s00109-019-01780-2DOI Listing
June 2019

Nutritional interventions and cognitive-related outcomes in patients with late-life cognitive disorders: A systematic review.

Neurosci Biobehav Rev 2018 12 3;95:480-498. Epub 2018 Nov 3.

Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Geriatric Unit, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia, Italy; Department of Clinical Research in Neurology, Center for Neurodegenerative Diseases and the Aging Brain, University of Bari "Aldo Moro", "Pia Fondazione Cardinale G. Panico", Tricase, Lecce, Italy. Electronic address:

There have been a large number of observational studies on the impact of nutrition on neuroprotection, however, there was a lack of evidence from randomized clinical trials (RCTs). In the present systematic review, from the 32 included RCTs published in the last four years (2014-2017) in patients aged 60 years and older with different late-life cognitive disorders, nutritional intervention through medical food/nutraceutical supplementation and multidomain approach improved magnetic resonance imaging findings and other cognitive-related biomarkers, but without clear effect on cognition in mild Alzheimer's disease (AD) and mild cognitive impairment (MCI). Antioxidant-rich foods (nuts, grapes, cherries) and fatty acid supplementation, mainly n-3 polyunsaturated fatty acids (PUFA), improved specific cognitive domains and cognitive-related outcomes in MCI, mild-to-moderate dementia, and AD. Antioxidant vitamin and trace element supplementations improved only cognitive-related outcomes and biomarkers, high-dose B vitamin supplementation in AD and MCI patients improved cognitive outcomes in the subjects with a high baseline plasma n-3 PUFA, while folic acid supplementation had positive impact on specific cognitive domains in those with high homocysteine.
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http://dx.doi.org/10.1016/j.neubiorev.2018.10.022DOI Listing
December 2018

Association of pleasant sensations at cigarette smoking initiation with subsequent tobacco product use among U.S. adolescents.

Addict Behav 2019 02 6;89:151-155. Epub 2018 Oct 6.

Department of Health Outcomes & Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, United States.

Approximately 20% of high school students and 7% of middle school students in the United States used tobacco products in 2016. One factor that may contribute to tobacco use is pleasant sensations - typically characterized as physiological reinforcement such as a dopamine response, or as social reinforcement such as social acceptance. In the present study, the Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study was analyzed to examine the influence of pleasant sensations at cigarette smoking initiation on current use of other tobacco products among adolescents. While those who reported higher unpleasant sensations at cigarette smoking initiation were less likely to report current use of any tobacco product(s) (Odds Ratio [OR] = 0.70), those who reported higher pleasant sensations at cigarette initiation were more likely to report current use of any tobacco product(s) (OR = 2.12) - including: cigarettes (OR = 2.09), cigars (OR = 1.58), hookah (OR = 1.37), and e-cigarettes (OR = 1.37). Based on these findings, interventions for smoking education and further surveillance may benefit adolescents who report higher pleasant sensations at cigarette smoking initiation.
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http://dx.doi.org/10.1016/j.addbeh.2018.10.003DOI Listing
February 2019

Nutritional Intervention as a Preventive Approach for Cognitive-Related Outcomes in Cognitively Healthy Older Adults: A Systematic Review.

J Alzheimers Dis 2018 ;64(s1):S229-S254

Department of Basic Medicine, Neurodegenerative Disease Unit, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.

The link diet-cognitive function/dementia has been largely investigated in observational studies; however, there was a lack of evidence from randomized clinical trials (RCTs) on the prevention of late-life cognitive disorders though dietary intervention in cognitively healthy older adults. In the present article, we systematically reviewed RCTs published in the last four years (2014-2017) exploring nutritional intervention efficacy in preventing the onset of late-life cognitive disorders and dementia in cognitively healthy subjects aged 60 years and older using different levels of investigation (i.e., dietary pattern changes/medical food/nutraceutical supplementation/multidomain approach and dietary macro- and micronutrient approaches) as well as possible underlying mechanisms of nutritional prevention. From the 35 included RCTs, there was moderate evidence that intervention through dietary pattern changes, medical food/nutraceutical supplementation, and multidomain approach improved specific cognitive domains or cognitive-related blood biomarkers. There was high evidence that protein supplementation improved specific cognitive domains or functional status in prefrail older adults without effect on cognitive function. For fatty acid supplementation, mainly long-chain polyunsaturated fatty acids, there was emerging evidence suggesting an impact of this approach in improving specific cognitive domains, magnetic resonance imaging (MRI) findings, and/or cognitive-related biomarkers also in selected subgroups of older subjects, although some results were conflicting. There was convincing evidence of an impact of non-flavonoid polyphenol and flavonoid supplementations in improving specific cognitive domains and/or MRI findings. Finally, there was only low evidence suggesting efficacy of intervention with homocysteine-related and antioxidant vitamins in improving cognitive functions, dementia incidence, or cognitive-related biomarkers in cognitively healthy older subjects.
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http://dx.doi.org/10.3233/JAD-179940DOI Listing
June 2019

Relationships of Dietary Patterns, Foods, and Micro- and Macronutrients with Alzheimer's Disease and Late-Life Cognitive Disorders: A Systematic Review.

J Alzheimers Dis 2017 ;59(3):815-849

Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.

In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed observational studies published in the last three years (2014-2016) on the relationship among dietary factors and late-life cognitive disorders at different levels of investigation (i.e., dietary patterns, foods and food-groups, and dietary micro- and macronutrients), and possible underlying mechanisms of the proposed associations. From the reviewed evidence, the National Institute on Aging-Alzheimer's Association guidelines for Alzheimer's disease (AD) and cognitive decline due to AD pathology introduced some evidence suggesting a direct relation between diet and changes in the brain structure and activity. There was also accumulating evidence that combinations of foods and nutrients into certain patterns may act synergistically to provide stronger health effects than those conferred by their individual dietary components. In particular, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline. Moreover, also other emerging healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets were associated with slower rates of cognitive decline and significant reduction of AD rate. Furthermore, some foods or food groups traditionally considered harmful such as eggs and red meat have been partially rehabilitated, while there is still a negative correlation of cognitive functions with saturated fatty acids and a protective effect against cognitive decline of elevated fish consumption, high intake of monounsaturated fatty acids and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA.
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http://dx.doi.org/10.3233/JAD-170248DOI Listing
April 2018