A blended e-health intervention for improving functional capacity in elderly patients on haemodialysis: A feasibility study.

Introduction: Physical exercise showed to be beneficial for frail older adults on haemodialysis (HD). However, there are several obstacles hindering the regular practice of exercise, such as transportation difficulties, lack of time, fatigue and comorbidities. E-health in this regard has many potential advantages and could be useful for motivating HD patients to increase their level of physical activity. The aim of this study was to evaluate the feasibility of a blended e-health intervention for elderly HD patients who individually exercise at home while under remote supervision of a physiotherapist. Material and methods: Patients over 60 years of age with sufficient cognitive and motoric resources to perform a simple physical test battery and to use a tablet-computer were recruited from four HD outpatient facilities. Following baseline assessment at home, the participants were visited by a physiotherapist (PT). The PT set an individual exercise programme and explained how to use the web-based interface. During the 12 weeks of training, the PTs remotely supervised the patients' progress. At 12 weeks follow-up a second assessment took place. Results: Twenty-two patients were recruited to participate in the study. Seven patients dropped out of the blended programme and 15 patients concluded the programme. The average training frequency of the 15 participants concluding the study was 1.5 times a week [range 0.2-5.8]. The duration of a training session was between 20 and 40 min. The usability of the system was deemed positive. Regarding the efficacy of the intervention, no significant improvement of any measured parameter was found, and effect sizes were small to medium. Conclusion: A blended e-health intervention supported by a web-based application for exercising at home under remote supervision of a PT is feasible in a HD population including older patients. However, before planning a randomized controlled trial, strategies to increase the recruitment rate and the adherence to such a blended intervention should be further developed, e.g., to improve the recruitment procedures and lower the expectable drop-out rate. Furthermore, the dosage of the blended programme should be adapted to the patients' physical performance levels in future trials.The study was registered on the website clinicaltrials.gov with ID NCT04076488.

Wish to Die Among Residents of Swiss Long-Term Care Facilities: A Multisite Cross-Sectional Study.

OBJECTIVES: The wish to die (WTD) in persons near the end of life is a clinically important, ethically and practically complex phenomenon as demonstrated by the intense debates on assisted dying legislation around the world. Despite global aging and increasing institutionalization in old age, WTD among residents of long-term care facilities (LTCF) is underexplored. We aimed to assess the prevalence of WTD and identify its predictors in older LTCF residents. DESIGN: Multisite cross-sectional observational study. SETTING AND PARTICIPANTS: 31 LTCF in the 3 major linguistic regions of Switzerland, including residents 75 years or older, admitted to the LTCF 4 to 10 months before the study, without severe cognitive impairment. METHODS: Between February 2013 and June 2017, trained research staff interviewed residents to assess WTD using 2 validated instruments and collected information on potential predictors, including depressive symptoms, anxiety, demoralization, feeling to be a burden, spiritual distress, symptom burden, multimorbidity, and drug use. Demographic data were obtained by chart review. Descriptive statistics as well as univariate and multivariate regression analyses were performed. RESULTS: From 427 eligible residents, 101 were excluded, 46 refused, and 280 were included in the study (acceptance rate 85.9%). In general, residents readily and openly addressed the topic of WTD. The prevalence of WTD was 16.0% and 16.2% according to the 2 instruments, with all but 1 of the residents expressing a passive WTD. The strongest independent predictors for a WTD were depressive symptoms (OR 7.45 and 5.77 for the 2 WTD assessment instruments) and demoralization (OR 2.62 and 3.66). CONCLUSIONS AND IMPLICATIONS: The WTD is a relevant concern affecting approximately 1 in 6 LTCF residents. Further research is needed to investigate which interventions could best address the potentially modifiable factors that were associated with the WTD in this specific setting and population.

A Pilot Observational Study Assessing Long-Term Changes in Clinical Parameters, Functional Capacity and Fall Risk of Patients With Chronic Renal Disease Scheduled for Hemodialysis.

BACKGROUND: Patients with end-stage renal disease are known to be particularly frail, and the cause is still widely seen as being directly related to specific factors in renal replacement therapy. However, a closer examination of the transitional phase from predialysis to long-term hemodialysis leads to controversial explanations, considering that the frailty process is already well-described in the early stages of renal insufficiency. This study aims to describe longitudinally and multifactorially changes in the period extending from the decision to start the replacement therapy through to the end of 2 years of hemodialysis. We hypothesized that frailty is pre-existent in the predialysis phase and does not worsen with the beginning of the replacement therapy. Between 2015 and 2018 we recruited 25 patients (72.3 ± 5.7 years old) in a predialysis program, with the expectation that replacement therapy would begin within the coming few months. METHODS: The patients underwent a baseline visit before starting hemodialysis, with 4 follow-up visits in the first 2 years of treatment. Health status, physical performance, cognitive functioning, hematology parameters, and adverse events were monitored during the study period. RESULTS: At baseline, our sample had a high variability with patients ranging from extremely frail to very fit. In the 14 participants that did not drop out of the study, out of 32 clinical and functional measures, a statistically significant worsening was only observed in the Short Physical Performance Battery (SPPB) score (p < 0.01, F = 8.50) and the number of comorbidities (p = 0.01, F = 3.94). A careful analysis, however, reveals a quite stable situation in the first year of replacement therapy, for both frail and fit participants and a deterioration in the second year that in frail participants could lead to death. CONCLUSION: Our results should stimulate a reassessment about the role of a predialysis program in reducing complications during the transitional phase, but also about frailty prevention programs once hemodialysis has begun, for both frail and fit patients, to maintain satisfactory health status.

Gait disorders in CKD patients: muscle wasting or cognitive impairment? A cross-sectional pilot study to investigate gait signatures in Stage 1-5 CKD patients.

BACKGROUND: Instrumental gait analysis in nephrology is widely neglected, although patients with chronic kidney disease (CKD) show brain changes due to cerebrovascular disease and metabolic disorders that can potentially influence gait quality. Our study assesses the association between CKD stages and gait parameters, to understand the prevalent status of brain related gait parameters (i.e. variability) and of performance related parameters (i.e. gait speed, stride length). We hypothesize that gait changes are detectable already in early stages of CKD. METHODS: Forty-five participants distributed in 5 CKD severity groups underwent an instrumental gait analysis via a triaxial accelerometer affixed to the lower trunk under single- and dual-task conditions. In addition to spatio-temporal parameters, variability and dual-task cost of gait were extracted. A battery of clinical assessments was conducted with the aim of helping to better explain the findings of the gait analysis. A correlation analysis was made to investigate a linear relation between gait parameters and CKD severity. RESULTS: Statistically significant correlations (Pearson correlation coefficient) with CKD severity were found for gait speed (p < 0.01, r = -0.55, 95% CI [-0.73;-0.30]), stride length ( p < 0.01, r = -0.40, 95% CI [-0.62;-0.12]), step length (p < 0.01, r = -0.41, 95% CI [-0.63;-0.13], coefficient of variance (CV) of step length (p = 0.01, r = 0.36, 95% CI [0.08;0.59]), gait regularity (p < 0.01, r = -0.38, 95% CI [-0.61;-0.10]), dual-task cost of gait speed (p < 0.01, r = 0.40, 95% CI [0.13;0.62]) and dual-task cost of stride time (p = 0.03, r = 0.32, 95% CI [0.03;0.57]). Adjustment for age and gender confirmed all results except for gait regularity. With increasing severity of renal failure, Handgrip strength, Time for the Expanded Timed Get Up and Go test, executive functions, haemoglobin, and haematocrit, worsen. CONCLUSIONS: The correlation of CKD severity with spatio-temporal parameters (performance indices mainly relatable to peripheral functionality) and with variability of gait (related to central factors) supported by the results of the clinical assessments, suggests that gait disturbance in CKD patients is not only due to metabolic factors that lead to muscle wasting, but also to brain changes that affect motor control. This suggests that the treatment of renal disease should include cognitive aspects in addition to metabolic and functional factors.

Signatures of Gait Movement Variability in CKD Patients Scheduled for Hemodialysis Indicate Pathological Performance Before and After Hemodialysis: A Prospective, Observational Study.

Background: The frailty status of hemodialysis patients is well-known, but the role of the therapy in the frailty process is not yet clear. Nowadays gait analysis in nephrology is neglected, although gait performance is known to be related to frailty and kidney function. We hypothesized that gait quality and physical activity level is already affected before, and does not change because of the start of hemodialysis. Methods: Fourteen patients (72.3 ± 5.7 years old) in a pre-dialysis program underwent an instrumental gait analysis and their physical activity was monitored for a week. This protocol was repeated 3, 6, 12, and 24 months after the first hemodialysis session. Results: At baseline, our sample showed a conservative gait with pathologic gait variability, high dual-task cost, and a sedentary lifestyle. No statistically significant change was found in any parameter in the analyzed period, but there was a tendency toward an improvement of gait quality and physical activity in the first year of treatment, and a decline in the second year. Conclusion: Elderly patients in the pre-dialysis stage show a conservative gait, however variability was in a pathological range and did not change post-hemodialysis. This hints toward changes in the central nervous system due to the kidney disease. This finding suggests the importance of gait analysis in the early stages of renal disease in the diagnosis of changes in the nervous system due to kidney failure that affect gait. Early detection of these changes would potentially allow a prevention program tailored to this population to be developed.

The role of diet on the risk of dementia in the oldest old: The Monzino 80-plus population-based study.

BACKGROUND & AIMS: Longevity also carries its dark side of age-related chronic diseases, dementia being one of the worst and the most prevalent. Since dementia lacks effective treatments, preventing or delaying it is highly desirable. Dietary habits and nutrition have been found to be important modifiable risk factors for many chronic diseases, but evidence on the role of diet on the risk of dementia is still limited, particularly among the very old. Aim of the present work is to study the association of the Mediterranean diet and its components with prevalent and incident dementia in the oldest-old. METHODS: We analyzed data from the Monzino 80-plus study, a population-based study in subjects 80 years or older in the Varese province, Italy. A validated food frequency questionnaire was used to collect information on 23 different foods consumed in the previous year. A Mediterranean diet score was calculated and its components were classified into tertiles. Multivariable models for dementia prevalence and incidence were adjusted for demographic and clinical characteristics. RESULTS: Information on nutrition was available for 1390 subjects in the cross-sectional study and 512 subjects in the longitudinal study, mean respective ages 93 and 92. Greater adherence to Mediterranean diet, greater consumption of eggs, fruits and vegetables, carbohydrates, and greater food intake were associated with a lower prevalence of dementia. Increasing number of portions per week and consumption of legumes significantly decreased the incidence of dementia during the 3.6 year mean follow-up: corresponding hazard ratios of highest vs. lowest tertiles (95% confidence intervals) were 0.66 (0.46-0.95) and 0.68 (0.47-0.97), respectively. CONCLUSION: Oldest-old eating less and having diets with less variety and nutrient density were more frequent among subjects with dementia. The longitudinal analysis confirmed oldest-old subjects who eat more portions, as well as those who have a higher intake of legumes, are at decreased risk of developing dementia even though reverse causality cannot be completely ruled out.

Gait characteristics of CKD patients: a systematic review.

BACKGROUND: People with Chronic Kidney Disease (CKD) often present with prevalent gait impairment and high fall rates, particularly in advanced CKD stages. Gait impairment and its consequences is associated with increased hospital admission, institutionalization, and greater need for health care. The objective of this systematic review was to evaluate the quality of studies investigating CKD patients' gait characteristics at different CKD stages, to highlight areas of agreement and contradiction between studies reporting aspects of gait in CKD, and to discuss and emphasize gait parameters associated with fall risk. METHODS: We performed a literature search of trials in CINAHL (EBSCO), Cochrane Library, EMBASE, Medline (EBSCO), PEDro, PubMed, and Scopus databases from their inception to June 30th 2018 using a two-stage process for the identification of studies. We retrieved English-, German-, Italian-, Spanish-, Portuguese and Dutch-language articles for review. Methodological quality of randomized and non-randomized studies was assessed with an adapted version of the Downs and Black checklist. RESULTS: Thirty-one studies (22 cross-sectional with 3901 participants) and 9 longitudinal intervention studies (1 randomized control trial, 5 controlled clinical trials and 3 one-group pre-post-test; with 659 participants) were considered. The studies revealed a primary emphasis on gait speed measures within clinical tests, and a neglect of spatiotemporal gait variables. Most of the studies showed that CKD progression is associated with slowing of walking speed. No studies analysed the relation between gait parameters and fall risk. CONCLUSIONS: There was a paucity of studies investigating aspects of gait quality in patients with CKD. In the majority of studies, only gait speed is analysed as a performance indicator. The relation between gait parameters and fall risk in CKD is not investigated. We formulate several recommendations to fill the current research gap, encourage the use of standardized gait analysis protocols that include assessment of spatiotemporal parameters in clinical care of patients with CKD, aimed at prevention of mobility decline and falls risk.

Clinical validity of novel postural stabilization experimental indices based on hyperbolic transformation.

BACKGROUND: Postural stabilization is the function which allows an individual, after a transitional movement, to recover balance in a quiet erect posture. An experimental method has been proposed (Rabuffetti, 2011) and proved valid for the assessment of balance disorders in individuals with neurological diseases. It would seem that the two original indices were not fully independent since their concurrent distribution was confined by a hyperbolic boundary. RESEARCH QUESTION: A methodological advancement involving non-linear transformation techniques is required to overcome the limitations of the original approach. METHODS: A hyperbolic transformation is applied to the original indices related to the mechanics of the stabilization (instability at beginning of stabilization and time rate of stabilization), thus defining two novel indices (Instability and Promptness). These novel indices may be related to different functional domains concerning, respectively, peripheral force capacity and central nervous motor control. The validity of these novel indices is quantified by their correlation with clinical scales in an already validated group of patients with Charcot-Marie-Tooth disease (N = 47) or Multiple Sclerosis (N = 20). RESULTS: The novel indices generally improved validity compared to the original indices (+66% of indices show a statistically significant concurrent validity on a clinical scale). Moreover, Instability was more related to the Charcot-Marie-Tooth group (9 out of 12 valid correlations), and Promptness to the Multiple Sclerosis group (4 out of 5, when also considering statistical trends), in accordance to the, respectively, more peripheral and more central nature of the two neurological diseases. SIGNIFICANCE: The novel postural stabilization indices support a clinical application for two reasons: 1) they have shown improved validity, compared to the original indices, in two groups of patients affected by neurological pathologies of different nature, 2) they are more closely related, compared to the original indices, to different functional domains.

SORL1 Gene is Associated with the Conversion from Mild Cognitive Impairment to Alzheimer's Disease.

Several studies have established the sortilin-related receptor gene (SORL1) as a susceptibility locus for Alzheimer's disease (AD). Single nucleotide polymorphisms of SORL1 reported in literature as being associated with AD were investigated in an Italian case-control data set, and their role as a risk factor of conversion to AD was studied in an independent sample of subjects diagnosed with mild cognitive impairment (MCI) at baseline. rs641120, rs2070045, and rs1010159 were genotyped in 734 subjects diagnosed with AD (n = 338) and MCI (n = 181) and in healthy controls (n = 215). Our results confirmed the association between rs641120 and AD (p = 0.01). In the MCI cohort, rs1010159 was associated with conversion to AD (HR = 1.56, p = 0.002). Taken together, these findings confirm that SORL1 is associated with AD and might be a potential tool for identifying MCI subjects at high risk of conversion to AD.

The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts.

BACKGROUND: Human sirtuins are a current hotspot for research in neurodegenerative disorders, including Alzheimer's disease (AD). This study investigated whether genetic variants in two members of the sirtuin family, SIRT2 and SIRT3, affected AD susceptibility. METHODS: A genetic case-control study was performed, comprising 534 probable AD cases and 638 nondemented control subjects from the north of Italy and Canton Ticino, Switzerland (discovery population). The study was focused on SIRT2 rs10410544, SIRT3 rs4980329, and SIRT3 rs536715 single nucleotide polymorphisms (SNPs). These SNPs were genotyped by real-time polymerase chain reaction allelic discrimination assay or restriction fragment length polymorphism. The SNPs rs7412 and rs429358, mapping within the apolipoprotein E (APOE) gene, were genotyped by real-time polymerase chain reaction allelic discrimination assay too. In a replication population comprising 756 AD cases and 847 nondemented control subjects, SIRT2 rs10410544, APOE rs7412, and APOE rs429358 were genotyped as mentioned previously. RESULTS: In the discovery population, we observed an association between SIRT2 rs10410544 T allele and AD (adjusted odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.02-1.50, P = .02, after correction for sex, age, and APOE ε4 genotype). The association between AD and SIRT2 rs10410544 T allele was only present in APOE ε4 noncarriers (adjusted OR = 1.29, 95% CI: 1.03-1.61, P = .03). The replication study did not confirm this evidence. However, the combined analysis on the two cohorts detected the association (adjusted OR = 1.17, 95% CI: 1.02-1.35, P = .02), and only APOE ε4 noncarriers were at risk (adjusted OR = 1.2, 95% CI: 1.02-1.43, P = .03). CONCLUSIONS: The SIRT2 rs10410544 T allele deserves further investigation as a novel minor genetic risk factor for AD in the APOE ε4-negative Caucasian population.

Postural stability and history of falls in cognitively able older adults: the Canton Ticino study.

Falls are common events in the elderly and represent the main risk factor for fractures and other injuries. Strategies for fall prevention rely on the multifactorial assessment of the risk of falling. The contribution of instrumented balance assessment to the prediction of falls remains unclear in the literature. In this study, we analyzed the association between the fall-history of a wide sample of older people without dementia and the values of a set of posturographic parameters acquired in different visual, proprioceptive and mental conditions. A consecutive sample of 130 cognitively able elderly subjects, age≥70 years, was analyzed. Based on their fall-history in the last year, subjects were categorized into non-fallers (NF), fallers (F) and recurrent fallers (RF>2 falls). Each subject was assessed by measurements of cognition and functional ability. Static posturography tests were performed in five conditions: with eyes open/close (EO/EC) on a firm/compliant (FS/CS) surface and while performing a cognitive task. The center of pressure (COP) mean position referred to the mid-point of the heels, area of the 95% confidence ellipse, sway mean velocities and RMS displacements in the antero-posterior (AP) and medio-lateral (ML) directions were computed and their association with the fall-history was assessed. The mean position of the COP in the AP direction and the confidence ellipse area were associated with the fall-history in the EOFS, ECFS and EOCS conditions (P<0.05). RMS displacements were also associated with the fall-history in the EOCS condition (P<0.05). Significant group differences (P<0.05) were found in the EOCS conditions, which greatly enhanced the differences among NF, F and RF. The ability to control balance while standing with eyes open on a compliant surface showed a high degree of association with the fall-history of older people with no or mild cognitive impairment.

Failure to replicate an association of rs5984894 SNP in the PCDH11X gene in a collection of 1,222 Alzheimer's disease affected patients.

A recent genome-wide study on late-onset Alzheimer's disease identified a SNP (rs5984894) on Xq21.3 in the PCDH11X gene strongly associated with LOAD individuals of European descent from the United States. We genotyped the same polymorphism in 1222 cases and 938 controls from central-northern Italy and could not confirm the association on the Italian population: multivariate logistic regression adjusted for gender and APOE epsilon4 allele resulted in a global p value of 0.56.

The urokinase-type plasminogen activator polymorphism PLAU_1 is a risk factor for APOE-epsilon4 non-carriers in the Italian Alzheimer's disease population and does not affect the plasma Abeta(1-42) level.

Sporadic Alzheimer's disease (AD) is the most frequent form of dementia in the elderly. A non-conservative polymorphism in the urokinase-type plasminogen activator gene (PLAU_1=RS2227564) has been analyzed, but data are conflicting on whether it is a risk factor for AD. To clarify whether this genetic variant modifies AD risk in the Italian population, we ran a case-control association study on 192 AD and 126 age-matched controls. We did not find any association between PLAU_1 genotype and AD in the whole AD population, but when we stratified our sample by APOE-epsilon4 status, we found a significant association between PLAU_1 genotype (C/T+T/T) and APOE-epsilon4 negative AD subjects (p=0.02, chi(2)-test). The PLAU_1 genotype did not appear to affect the plasma Abeta42 concentration. Our data support a role for PLAU_1 as an independent genetic risk factor for AD in the Italian population for those subjects who do not have the APOE-epsilon4 allele.

Plasma levels of beta-amyloid (1-42) in Alzheimer's disease and mild cognitive impairment.

We compared plasma levels of beta-amyloid 1-42 (pg/ml) found for 146 sporadic Alzheimer (AD) patients, 89 subjects with mild cognitive impairment (MCI) and 89 age-matched controls (CT). AD patients had significantly lower levels (38, 54, 52; p<0.01), unrelated to severity of the disease as assessed by MMSE score, age, sex or APOE4 status. Twenty cases investigated at two time points 18 months apart did not demonstrate further decreases. Thus, the reduction in beta-amyloid 1-42 may be a marker for AD status, specifically, a transition from normal status or MCI to AD, rather than a marker for neurodegenerative processes occurring in the disease.

Homocysteine and B vitamins in mild cognitive impairment and dementia.

Elderly subjects with mild cognitive impairment have a high risk for conversion to Alzheimer's disease or are already in a preclinical dementia stage. By cross-sectionally comparing subjects in prodromal and early phases of dementia with non-demented controls, we tested the hypothesis whether low serum vitamin B12 and folate and high plasma total homocysteine concentrations precede or are a consequence of dementia onset. From a large population of 623 consecutive subjects seen at the Memory Clinic (Ospedale Beata Vergine, Mendrisio, Switzerland), 433 subjects could be included in the analyses: 79 elderly controls, 218 Clinical Dementia Rating 0.5 subjects, and 136 demented patients (111 with Alzheimer's disease and 25 with vascular dementia). As in an earlier report on a smaller sample of the same population (n=228), the lowest folate tertile was strongly associated with mild cognitive impairment (adjusted OR=3.1) and Alzheimer's disease (adjusted OR=4.0). Hyperhomocysteinemia showed a significant association not only with Alzheimer's disease (adjusted OR=3.1) but, at variance with the previous report, also with mild cognitive impairment (adjusted OR=2.6). Present reanalysis results suggest that subclinical folate deficiency and hyperhomocysteinemia might predate dementia onset, findings to be confirmed by longitudinal studies.

Lower limb function as predictor of falls and loss of mobility with social repercussions one year after discharge among elderly inpatients.

BACKGROUND AND AIMS: Poor mobility of the lower limbs in community-dwelling elderly people is a predictor of functional decline in terms of disability, falls, nursing home admission, and death. However, its predictive value has not been studied in acute care hospital settings. The aims of this observational, prospective study were: 1) to assess the prognostic value of lower limb function; and 2) to compare the predictive value of three performance tests in elderly inpatients. METHODS: We studied 144 patients aged 70 or older (60 men and 84 women, mean age 78.7 +/- 5.6 years), admitted consecutively to a general internal medicine ward. Before discharge, patients underwent multidimensional assessment, including static and dynamic equilibrium and gait, by the Performance-Oriented Mobility Assessment (POMA), Short Physical Performance Battery (SPPB), and Functional Reach (FR). One-year outcomes were falls, loss of mobility with social repercussions (inability to leave home, or need for nursing home care) and death. RESULTS: In univariate analysis, poor results on any of the three tests were associated with an increased risk of falls, loss of mobility with social repercussions, and death. In multivariate analysis, age, two or more falls, and a low POMA score were predictive of future falls, whereas dependency in instrumental activities of daily living and a low SPPB score were predictive of loss of mobility with social repercussions. No multivariate model was superior to univariate ones in predicting death. No associations were found between other medical or geriatric characteristics and outcomes. CONCLUSIONS: Lower limb mobility tests performed in an acute care hospital setting are predictive of future falls, inability to leave home, and/or need for nursing home care.

Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia.

BACKGROUND: Evidence supports an independent association between plasma total homocysteine concentrations and the risk of vascular disease. Recent epidemiologic studies reappraised the possibility that vascular risk factors might play a role in the pathogenesis not only of vascular dementia (VaD) but also of Alzheimer disease (AD). OBJECTIVE: The objective was to investigate the relations of mild cognitive impairment, AD, and VaD with blood homocysteine, folate, and vitamin B-12. DESIGN: The study population consisted of 314 consecutive subjects, 228 of whom were eligible for analyses. Plasma total homocysteine, serum folate, and serum vitamin B-12 concentrations were measured in 55 nondemented elderly control subjects, 81 mildly cognitively impaired subjects (Clinical Dementia Rating: 0.5), and 92 demented patients prevalently in a mild disease stage and with a clinical diagnosis of AD (n = 74) or VaD (n = 18). RESULTS: Subjects in the lowest folate tertile had significantly higher adjusted odds ratios (ORs) for mild cognitive impairment (OR: 3.1; 95% CI: 1.2, 8.1) and dementia (3.8; 1.3, 11.2). Hyperhomocysteinemia was significantly associated with dementia (adjusted OR: 4.3; 1.3, 14.7) and AD (adjusted OR: 3.7; 1.1, 13.1). In subjects with a Clinical Dementia Rating of 0.5, the mean (+/- SE) Mini-Mental State Examination score was significantly lower (P < 0.05) in the highest homocysteine tertile (24.5 +/- 0.5) than in the lowest tertile (26.6 +/- 0.5). No significant associations were found between minimum medial temporal lobe thickness or leukoaraiosis and any biochemical measure in the dementia and AD groups. CONCLUSIONS: These findings suggest that relative folate deficiency may precede AD and VaD onset. Hyperhomocysteinemia might also be an early risk factor for cognitive decline in the elderly, but its role in dementia development must be addressed in future longitudinal studies.

Tumor necrosis factor alpha polymorphism C-850T is not associated with Alzheimer's disease and vascular dementia in an Italian population.

A pathogenic role of inflammatory factors has been proposed both in Alzheimer's disease (AD) and vascular dementia (VD). A previous report indicated the presence of polymorphism C-850T of tumor necrosis factor (TNF) alpha as a genetic risk factor for VD and, associated with apolipoprotein E epsilon 4, for AD. We have assessed the association between TNF-alpha polymorphism and dementias in Italian populations of AD, VD and elderly controls. The influence of TNF-alpha polymorphism on dementia has not been confirmed in this segment of the Italian population.