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Imbimbo B.P.,Chiesi Farmaceutici | Solfrizzi V.,University of Bari | Panza F.,Geriatric Unit and Gerontology Geriatrics Research Laboratory
Frontiers in Aging Neuroscience

Several epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect subjects carrying one or more ε4 allele of the apolipoprotein E (APOE ε4) against the onset of Alzheimer's disease (AD). The biological mechanism of this protection is not completely understood and may involve the anti-inflammatory properties of NSAIDs or their ability of interfering with the β-amyloid (Aβ) cascade. Unfortunately, long-term, placebo-controlled clinical trials with both non-selective and cyclooxygenase-2 (COX-2) selective inhibitors in mild-to-moderate AD patients produced negative results. A secondary prevention study with rofecoxib, a COX-2 selective inhibitor, in patients with mild cognitive impairment was also negative. A primary prevention study (ADAPT trial) of naproxen (a non-selective COX inhibitor) and celecoxib (a COX-2 selective inhibitor) in cognitively normal elderly subjects with a family history of AD was prematurely interrupted for safety reasons after a median period of treatment of 2 years. Although both drugs did not reduce the incidence of dementia after 2 years of treatment, a 4-year follow-up assessment surprisingly revealed that subjects previously exposed to naproxen were protected from the onset of AD by 67% compared to placebo. Thus, it could be hypothesized that the chronic use of NSAIDs may be beneficial only in the very early stages of the AD process in coincidence of initial Aβ deposition, microglia activation and consequent release of pro-inflammatory mediators. When the Aβ deposition process is already started, NSAIDs are no longer effective and may even be detrimental because of their inhibitory activity on chronically activated microglia that on long-term may mediate Aβ clearance. The research community should conduct long-term trials with NSAIDs in cognitively normal APOE ε4 carriers. © 2010 Imbimbo, Solfrizzi and Panza. Source

Premi E.,University of Brescia | Archetti S.,III Laboratory of Analyses | Pilotto A.,University of Brescia | Seripa D.,Geriatric Unit and Gerontology Geriatrics Research Laboratory | And 3 more authors.
Neurobiology of Aging

In frontotemporal dementia (FTD), nonmodifiable (genetic background) and modifiable (cognitive reserve [CR]) factors might interact in affecting frontotemporal damage. Serotoninergic dysfunction has been suggested as a key factor in FTD pathogenesis. 5-HTTLPR polymorphism on SCLA4 gene modulates the serotoninergic transmission. To evaluate the impact of 5-HTTLPR polymorphism on regional cerebral blood flow (rCBF) and its possible interaction with CR, 76 FTD patients with a 5-HTTLPR genotyping were recruited. All subjects underwent neuropsychological assessment and single-photon emission computed tomography imaging. Reserve index (RI) was computed from educational and occupational attainments, as proxy measure of CR. 5-HTTLPR analysis evidenced 14 S/S, 24 L/L, and 38 S/L carriers. No neuropsychological/behavioral differences were present. At the same disease stage, L/L carriers have a greater bilateral frontal rCBF decrease. Patients with higher RI had greater damage in right frontal and temporal regions. The additive effect of 5-HTTLPR polymorphism and RI was characterized by greater frontal rCBF deficit. 5-HTTLPR and CR act together to counteract brain pathology in FTD. Further studies are warranted to test the serotonin role in monogenic forms of FTD. © 2015 Elsevier Inc. Source

Pilotto A.,Geriatric Unit and Gerontology Geriatrics Research Laboratory | Maggi S.,National Research Council Italy | Noale M.,National Research Council Italy | Franceschi M.,Geriatric Unit and Gerontology Geriatrics Research Laboratory | And 2 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences

BackgroundSeveral diagnostic questionnaires for evaluating upper gastrointestinal symptoms have been described; none of these, however, has been validated in older individuals.ObjectivesTo develop and validate a diagnostic tool for evaluating upper gastrointestinal symptoms in older patients.MethodsA cohort of 206 older patients who underwent a upper gastrointestinal endoscopy (development cohort) was used for developing a 15-item upper gastrointestinal symptom questionnaire for the elderly population (UGISQUE), including five symptom clusters: (a) abdominal pain syndrome, (b) reflux syndrome, (c) indigestion syndrome, (d) bleeding, and (e) nonspecific symptoms. The questionnaire was then validated in a cohort of 326 older patients selected from those who underwent an upper gastrointestinal endoscopy in 15 gastroenterological centers in Italy (validation cohort).ResultsThe endoscopic diagnoses in the development and validation cohorts were esophagitis (E) 15.5% and 29.4%, erosive gastritis (EG) 24.8% and 24.8%, peptic ulcer (PU) 26.2% and 14.7%, and without organic lesions (WOL) 31.0% and 33.5%, respectively. In both the cohorts, patients with upper gastrointestinal disorders showed significantly more symptoms than WOL patients. The predictive value of UGISQUE for any pathological condition (E, EG, or PU) was good, with areas under the receiver-operating characteristic curve of. 80, 95% confidence interval (CI) 0.743-0.864, and of. 78, 95% CI 0.73-0.83, in the development and validation cohorts, respectively. The accuracy of UGISQUE was significantly higher than that for the individual clusters of symptoms in predicting the presence of E (p =. 004), PU (p <. 0001), or any pathological condition (p <. 0001).ConclusionUGISQUE is an accurate diagnostic tool for evaluating symptoms in elderly patients with upper gastrointestinal disorders. Source

Greco A.,Geriatric Unit and Gerontology Geriatrics Research Laboratory | Paroni G.,Geriatric Unit and Gerontology Geriatrics Research Laboratory | Seripa D.,Geriatric Unit and Gerontology Geriatrics Research Laboratory | Addante F.,Geriatric Unit and Gerontology Geriatrics Research Laboratory | And 2 more authors.
Kidney and Blood Pressure Research

Frailty in the elderly is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. It is usually associated to adverse health outcomes and to one-year mortality risk. Physical exercise has found to be effective in preventing frailty and disability in this population. Chronic kidney disease (CKD) is also a clinical condition where protein energy-wasting, sarcopenia and dynapenia ,very common symptoms in the frail elderly, may occur. Moreover elderly and CKD patients are both affected by an impaired physical performance that may be reversed by physical exercise with an improvement of the survival rate. These similarities suggest that frailty may be a common pathway of aging and CKD that may induce disability and that can be prevented by a multidimensional approach in which physical exercise plays an important role. © 2014 S. Karger AG, Basel. Source

Panza F.,Geriatric Unit and Gerontology Geriatrics Research Laboratory | Solfrizzi V.,University of Bari | Frisardi V.,University of Bari | Maggi S.,CNR Institute of Neuroscience | And 4 more authors.
Journal of Nutrition, Health and Aging

Dementia is an increasingly common disease in the aging population, and the numbers are expected to rise exponentially in coming years. Therefore, there is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Despite a substantial increase in the epidemiological and clinical evidence on frailty, there is no consensus on its definition or on what criteria should be used to identify older individuals with frailty. Frailty appears to be a nonspecific state of vulnerability, which reflects multisystem physiological change. In fact, current thinking is that not only physical but also psychological, cognitive and social factors contribute to this multidimensional syndrome and need to be taken into account in its definition and treatment. Cognition has already been considered as a component of frailty, and it has been demonstrated that it is associated with adverse health outcomes. In a recent population-based study, physical frail demented patients were at higher risk of all-cause mortality over 3- and 7-year follow-up periods. Several studies have also reported that physical frailty is associated with low cognitive performance, incidence of Alzheimer's disease (AD), and mild cognitive impairment, and AD pathology in older persons with and without dementia. Most frailty instruments use a dichotomous scoring system classifying a person as either frail or not frail, while a continuous or an ordinal scoring system on multiple levels would be preferable to be used as an outcome measure. Recently, a Multidimensional Prognostic Index (MPI), derived from a standardized comprehensive geriatric assessment, was effective in predicting short- and long-term mortality risk in hospitalized patients with dementia. Overall taken together these findings supported the concept that outcome measures linked to multidimensional impairment may be extremely important in making clinical decisions, especially for monitoring drug treatment in randomized clinical trials also for predementia and dementia syndromes. © 2011 Serdi and Springer Verlag France. Source

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