Francesco Panza

..However, contrasting findings also exist...

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..New APP-selective γ-secretase inhibitors are being developed with the hope of overcoming the previous setbacks...

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..In this scenario, at least in certain subsets of elderly patients, late-life depression, MCI, and dementia could represent a possible clinical continuum...

..We evaluated the impact of depressive symptoms on the rate of incident mild cognitive impairment (MCI) after a 3.5-year follow-up, and we assessed the interaction between depressive symptoms and vascular risk factors for incident MCI...

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..5-year follow-up; and the interaction between depressive symptoms and vascular risk factors for conversion to dementia...

..While further studies are needed to confirm the possible role of apolipoprotein E concentration as putative longevity factor this paper provides an overview of many of the investigated vascular factors with respect to longevity...

..At present, vascular risk factor management could be decisive in delaying the onset of dementia syndromes or in preventing the progression of predementia syndromes...

..At present, vascular risk factor management, lifestyle changes, and drugs could be employed together to delay the onset of dementia syndromes...

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..g., 3-5 years of follow-up)...

..The results of four ongoing large Phase III trials on bapineuzumab will provide answers regarding whether passive anti-Aβ immunization is able to alter the course of this devastating disease...

..Global cognitive function and episodic memory at baseline were not associated with the course of depressive symptoms during the follow-up...

..This article briefly reviews the profile of γ-secretase inhibitors, compounds that inhibit γ-secretase, the pivotal enzyme that generates Aβ, and that have reached the clinic...

..All these therapeutic approaches increase the hope of slowing the rate of decline in patients with AD and modifying the natural history of this devastating disease within the next 5 years...

..With all these approaches on their way, the hope for disease-modifying therapy in this devastating disease may become a reality in the next 5 years...

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..This review will focus on the possible role of vascular risk factors in modulating the risk of age-related cognitive decline, and the progression of predementia syndrome such as MCI to dementia...

..We suggest that these regional variations in LRP1 genotype and allele frequencies in AD could be related to the different patterns of association between this polymorphism and the disease in various European studies...

..This review will focus on the current knowledge on genetic and nongenetic vascular factors likely to be involved in LOAD, with special emphasis placed on the APOE and ACE1 genes...

..To clarify the sources of discrepant findings in the literature, this review summarizes existing epidemiological studies of the defined clinical predementia syndromes and their progression to dementia...

..Such genetic differences in conjunction with differing environmental factors may explain in part previous results suggesting a role of this polymorphism in longevity...

..In these highly selected populations, APOE genotype distribution strongly influences serum APOE concentration, not suggesting, at present, a possible role as a biochemical marker for AD, but only as a putative longevity factor...

..In this article, we focused on the current knowledge of the genetics of familial late-onset and sporadic AD linked to the chromosome 12, and the future search for other candidate genes...

..Thus, more studies with long-term follow-up and serial assessments of TC are needed to further clarify the causal relationship between cholesterol and dementia...

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..Further understanding of the reasons of the failures of these γ-secretase-based drugs in AD may be important for the future research on effective treatments for this devastating disease...

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..While further studies are needed to confirm the possible role of APOE concentration as putative longevity factor, this paper provides an overview of genetic vascular factors potentially involved in human longevity...

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..Furthermore, the C allele of the IL-6 variable number of tandem repeats (VNTR) polymorphism was associated with a delayed onset and a decreased risk of AD...

..Our data, at present, do not support a role of two gene polymorphisms of the short arm of the chromosome 11, the CAT rs1001179 and CTSD rs17571, as a possible susceptibility factors for sporadic AD...

..Less clear are data regarding their association with severe dementia, in particular with vascular dementia (VaD)...

..Neuropsychiatric symptoms (NPS) are a common feature of Alzheimer's disease (AD), resulting in particular AD endophenotypes. The common AD genetic risk factor apolipoprotein E (APOE) has been suggested underlying these AD endophenotypes...

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..89, 95% CI 1.10-3.44), but not of disability. Frailty syndrome was a short-term predictor of disability in nondemented older subjects and short- and long-term predictor of all-cause mortality in nondemented and demented patients...

..The regional differences in CTSD allele frequencies could be related to the different patterns of association between this polymorphism and AD in various European studies...

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..In our population, among MCI patients the presence of MetS independently predicted an increased risk of progression to dementia over 3.5 years of follow-up...

..No further differences among the three groups of subjects were found, also when they were compared with the community-dwelling sample. These findings suggest that SLC6A4 gene variation may have only a minor role, if any, in AD or QD...

..34-1.13, p=0.12). In our population, dietary fatty acids intakes were not associated with incident MCI in older age, only high PUFA intake evidenced a borderline nonsignificant trend for a protective effect against the development of MCI...

..In our population, the +1073 C/T OLR1 polymorphism exhibited a significant association with Alzheimer's disease, further supporting the role of OLR1 as a candidate risk gene for sporadic Alzheimer's disease...

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..In fact, identifying predisposing genetic risk factors may allow us to understand the pathophysiological features of neuropsychiatric syndromes or symptoms in AD, so optimizing possible therapeutic options...

..At present, there is no indication that light to moderate alcohol drinking would be harmful to cognition and dementia, and it is not possible to define a specific beneficial level of alcohol intake...

..5-year follow-up. In this prospective population-based study on older nondemented subjects with a typical Mediterranean diet, high MUFA and PUFA intakes appeared to be protective against ARCD...

..In conclusion, in our population, among MCI patients who progressed to dementia, 60% progressed to AD and 33% to VaD. Vascular risk factors and CVD may influence the development of MCI and the rate of progression to dementia...

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..In the future, trials could be undertaken to determine whether modifications of these risk factors, including inflammation, could lower risk of developing cognitive decline...

..We estimated the prevalence and incidence rates of depressive symptoms and the role of vascular risk factors and sociodemographic variables on the occurrence of depressive symptoms in mild cognitive impairment (MCI)...

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..014,; 95% CI, 2.528-6.382). Our findings supported a role of the GSTO1 rs4925 SNP in the risk of sporadic AD in southern Italy, suggesting that this and other variants of the GSTO1 gene could be implicated in AD pathogenesis...

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..62 and 0.91, respectively. The SCT is a valid and reliable test to assess selective attention in elderly subjects, in whom dementing illness must be diagnosed and clinically distinct from age-related cognitive decline...

..636). Heterosis was also observed at the ACE locus. No relationship between apoE and ACE polymorphism was found. These findings suggest a role of sex in the association of apoE and ACE gene polymorphisms with healthy aging and longevity...

..Hopefully this will open new opportunities for the prevention and management of dementia and AD...

..The authors investigated the relationship of metabolic syndrome (MetS) and its individual components with incident dementia in a prospective population-based study with a 3.5-year follow-up...

..Therefore, at present, no definitive dietary recommendations on fish and unsaturated fatty acids consumption, or lower intake of saturated fat, in relation to the risk for dementia and cognitive decline are possible...

..In conclusion, the MPI, calculated from information collected in a standardized CGA, accurately stratified hospitalized elderly patients with dementia into groups at varying risk of short- and long-term mortality...

..However, it is still unclear if a relationship exists between the APOE epsilon4 allele and vascular dementia (VaD) in elderly subjects...

..In conclusion, in this prospective study on older nondemented subjects with a typical Mediterranean diet, a higher MUFA intake increased survival, while a higher UFA/SFA ratio increased total mortality, but only marginally...

..We suggest that regional European differences in genotype and allele frequencies of the IL-6-174 G/C promoter polymorphism may explain in part controversial findings on this polymorphism in AD in various European studies...

..These findings suggest that RELN gene variants may play a role in the pathogenesis of AD, particularly in females...

..Finally competing risk, conditioning the timing and occurrence of vascular events in our study population, could be a correct approach for evaluating the role of Lp(a) lipoprotein in vascular disease among elderly people...

..Glutamate transmits signals via the N-methyl-D-aspartate receptors (NMDARs). Aims: The potential involvement of polymorphisms in the GRIN2B gene, encoding subunit 2B of the NMDA receptor, in the risk for AD was evaluated...

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..To investigate the role of the apolipoprotein E (APOE) locus in frontotemporal dementia (FTD) and primary progressive aphasia (PPA)...