Subjective Cognitive Decline as a predictor of Frailty in older adults: Hellenic Longitudinal Investigation of Aging and Diet study (HELIAD).

BACKGROUND: Subjective cognitive decline (SCD) is a self-evaluation of cognitive impairment, in the absence of observed objective cognitive deficits on a neuropsychological assessment. Frailty refers to a multidimensional syndrome where the individual has poor health including falls, disabilities, hospitalization, and vulnerability. Both terms are associated with cognitive decline and increased incidence of dementia. The present longitudinal study explored whether the detection of SCD can predict the development of frailty over time. METHODS: The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) is an epidemiological, population-based study. From the original testing sample of 1,984 older Greek individuals (≥65 years old), 1,121 remained in the longitudinal analysis. Participants diagnosed with frailty, Mild Cognitive Impairment (MCI), dementia, severe depression, and anxiety, in the baseline assessment were excluded from the analysis (n=146), resulting in a total sample of 975 participants. The average follow-up interval was 3.1 years (SD=0.84 years). SCD was assessed in the baseline assessment with a series of eighteen questions. The questions regarding SCD were categorized according to cognitive domains. Frailty was assessed according to a phenotypic-physiologic (Fried's definition) and a multidomain approach (Frailty Index). Univariate and multivariate Cox regression analyses were used for exploring the role of SCD in developing frailty. RESULTS: The proportion of individuals with frailty according to Fried's definition was greater compared to the Frailty Index. At follow-up according to Fried's definition, a greater proportion of cases with frailty was found in those who reported SCD complaints regarding orientation (OD) (HR=3.12 95% CI:1.45-6.73 p<0.004) or in those who reported at least three SCD complaints regarding their memory performance (SMC3) (HR=1.92 95% CI:1.05-3.52 p<0.035) at the baseline assessment. Subjective complaints regarding orientation were predictive of a greater hazard of frailty as defined by the Fried scale (HR=3.12 95% CI:1.45-6.73 p<0.004) and the Frailty Index (HR=3.59 95% CI:1.77-7.25 p<0.001). CONCLUSION: Our findings demonstrate that healthy older adults who report SCD complaints regarding orientation or state that they have at least three memory complaints have a higher risk of developing frailty. Additionally, the number of participants with a clinical diagnosis of MCI or dementia, compared to individuals with normal aging, at follow-up was found to be significantly greater in cases with frailty according to both frailty definitions applied (p<0.001). Consequently, it is advisable to use screening questionnaires for SCD covering multiple cognitive domains in clinical practice for identifying and managing frailty, thus, implementing effective interventions to promote healthy aging.

Sleep Quality and Duration as Determinants of Healthy Aging Trajectories: The HELIAD Study.

BACKGROUND: The aging of global population has increased the scientific interest in the concept of healthy aging and its determinants. AIM: The aim of this study was to investigate the association of sleep characteristics with trajectories of healthy aging. DESIGN AND SETTING: Prospective observational study conducted in two cities, Maroussi and Larissa. PARTICIPANTS: A total of 1226 older adults (≥65 years, 704 women) were selected through random sampling. MEASUREMENTS: Sleep quality was assessed with the Sleep Index II, and sleep duration was self-reported. A healthy aging metric was introduced using an Item Response Theory approach based on validated questionnaires that assessed functionality. Four healthy aging trajectories were developed based on whether the healthy aging status of the participants was above (High) or below (Low) the median at baseline and follow-up, i.e., High-High, High-Low, Low-High, and Low-Low. The association of sleep characteristics with the trajectories was investigated using a multinomial logistic regression with the Low-Low group as reference, adjusting for potential confounders. RESULTS: 34.3% participants classified to the High-High group, 15.7% to the High-Low, 18.6% to the Low-High, and 31.4% to the Low-Low group. Better sleep quality was associated with the probability of belonging to the High-High group (p-value<0.001); while, long sleep duration was inversely associated with likelihood of being classified in the High-High group (p-value < 0.05). CONCLUSION: Poor sleep quality and long sleep duration seem to have a significant negative association with healthy aging. Public health policies are needed to raise awareness about the importance of sleep characteristics on human health.

Objective and Subjective Measurements of Motor Function: Results from the HELIAD Study.

BACKGROUND: Slow gait speed has recently emerged as a potential prodromal feature of cognitive decline and dementia. Besides objective measurements, subjective motor function (SMF) difficulties might be present prior to the manifestation of gait disorders. OBJECTIVES: To examine the association of walking time and the presence of SMF with future cognitive decline in cognitively normal individuals. DESIGN: Longitudinal study. SETTINGS: Athens and Larissa, Greece. PARTICIPANTS: 931 cognitively normal individuals over the age of 64 with longitudinal follow-up from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). MEASUREMENTS: We used a simple chronometer for recording objective walking time (OWT) and SMF was assessed using a self-reported physical functioning questionnaire. Generalized estimating equations (GEE) models were deployed to explore the associations between baseline OWT and SMF difficulties and the rate of change of performance scores on individual cognitive domains over time. Models were adjusted for age, years of education and sex. RESULTS: Each additional second of OWT was associated with 1.1% of a standard deviation more decline per year in the composite z-score, 1.6% in the memory z-score, 1.1% in the executive z-score and 1.8% in the attention-speed z-score. The presence of SMF difficulties was not associated with differential rates of decline in any cognitive domain. CONCLUSION: Gait speed can be indicative of future cognitive decline adding credence to the notion that gait speed might serve as a simple and easily accessible clinical tool to identify a larger pool of at risk individuals and improve the detection of prodromal dementia.

Sex Differences in Frailty Incidence in Greek Community-Dwelling Older People: The HELIAD Study.

BACKGROUND: Previous frailty studies found higher prevalence of frailty in female than in male participants. This was mainly attributed to the fact that compared to men, women show increased longevity. Recent studies have reported that the observed difference between sexes applies irrespectively of the age of older people. OBJECTIVES: To provide data on sex differences in incident frailty by applying both phenotypic and multi-domain frailty measures in the same population of Greek community-dwelling older people. DESIGN: Longitudinal study. SETTING: Data were drawn from the Hellenic longitudinal Investigation of Aging and Diet (HELIAD), a population-based, multidisciplinary study designed to estimate the prevalence and incidence of dementia in the Greek population. PARTICIPANTS: 1104 participants aged 65 year and above were included in this longitudinal study. This incidence cohort was re-evaluated after a mean follow-up period of 3.04±0.90 years. MEASUREMENTS: Frailty was operationalized using 5 different definitions in the same population: the Fried Frailty Phenotype (FFP) definition, the FRAIL Scale, the Frailty Index (FI), the Tilburg Frailty Indicator (TFI) and the Groningen Frailty Index (GFI). Frailty incidence was calculated a) for the whole sample, b) separately for men and women and c) after both age and sex stratification. RESULTS: Age and sex stratification revealed that irrespective of age and frailty measurement, women showed higher incidence rates of frailty than men. Specifically, frailty seems to be a condition concerning women >65 years old, but when it comes to men, it is more frequent in those aged more than 75 years old. Finally, in relation to overall frailty incidence and comparing our results to previous studies, we detected a lower frailty incidence in the Greek population. CONCLUSIONS: Differences between the two sexes indicate that when exploring the factors that are related to frailty, studies should provide data disaggregated for men and women.

Adherence to the Mediterranean diet and incident frailty: Results from a longitudinal study.

OBJECTIVES: The aim of the current prospective study was to examine the relationship between adherence to the Mediterranean diet and incident frailty. STUDY DESIGN: 1075 Greek community-dwelling older adults from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present longitudinal analysis. MAIN OUTCOME MEASURES: Adherence to the Mediterranean diet was evaluated through the MedDietScore, calculated from the information participants provided on a validated food frequency questionnaire. Frailty was assessed using two multidomain tools: the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI). Analysis of the incidence of frailty as a function of the baseline MedDietScore was performed using Cox proportional hazards models. Additionally, Generalized Estimating Equations (GEE) models were used to explore whether the baseline MedDietScore was associated with the change in the total number of frailty criteria met by participants over time. In testing for a dose-response association between Mediterranean diet and frailty, the MedDietScore was treated either as a continuous variable or as tertiles of low, medium and high adherence to MeDi. RESULTS: 176 and 131 participants developed incident frailty, as measured with the FI and TFI respectively. Each unit of MedDietScore was associated with a 5% (ΗR 0.95, 95% CI 0.91-0.99, p = 0.012) and 10% (ΗR 0.90, 95% CI 0.86-0.95, p ≤ 0.001) decrease in the risk of incident frailty when measured with the FI and TFI respectively. Compared with participants reporting low adherence to the Mediterranean diet (lowest tertile), those with high adherence (highest tertile) had a 41% (ΗR 0.59, 95% CI 0.38-0.91, p = 0.017) and a 57% (ΗR 0.43, 95% CI 0.27-0.70, p ≤ 0.001) lower risk of incident frailty as measured with the FI and TFI respectively. After excluding from the analyses participants diagnosed with dementia at baseline or follow-up, the same results were obtained: each unit of MedDietScore was associated with a 5% (HR 0.95 CI 0.91-0.99, p = 0.023) and a 10% (HR 0.90 CI 0.86-0.94, p ≤ 0.001) decrease in the risk of incident frailty as measured with the FI and TFI respectively. CONCLUSIONS: The present longitudinal study showed that non-frail community-dwelling older adults with high adherence to the Mediterranean dietary pattern had a significantly lower incidence of frailty.

Association between 9p21-23 Locus and Frailty in a Community-Dwelling Greek Population: Results from the Hellenic Longitudinal Investigation of Ageing and Diet.

BACKGROUND: Frailty is a complex geriatric syndrome arising from a combination of genetic and environmental factors and is associated with adverse health outcomes and mortality. A recent study reported an association between variants of the 9p21-23 locus, associated with a number of age-related disorders, including Alzheimer's disease (AD), and frailty. Frailty has been associated with increased risk of developing AD and it has been proposed that frailty burden may modify AD clinical presentation. In view of the overlapping genetic architecture between the two disorders, it is noteworthy to conduct studies to uncover risk variants that contribute to both AD and frailty. The purpose of this study is to test the reproducibility of the association of 9p21-23 locus with frailty in a population that is ethnically different from previous work and in the context of multidimensional definitions of frailty that will allow us to examine the potential impact to domains pertaining to AD pathology. METHODS: We operationalized frailty according two definitions and the corresponding instruments, the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI) and we determined genotypes of eight alleles previously identified as risk increasing for frailty in 1172 community-dwelling older participants (57% females) from the HELIAD study with a mean age of 74 years old. We cross-sectionally investigated the association between risk alleles and frailty, as well as with specific components of each definition using linear regression analyses adjusted for age, sex and years of education. RESULTS: Compared to non-carriers, carriers of rs7038172 C risk allele, were associated with a higher FI Score (ß=0.089, p=0.002). Similarly, we found a positive association between the presence of at least one rs7038172 C variant and TFI score (ß=0.053, p=0.04). Moreover, the rs7038172 variant was associated, irrespectively of dementia status, with the memory and psychological domain of FI and TFI, respectively. CONCLUSION: Our study confirms the association of the rs7038172 C allele with the frailty syndrome in a Greek population and in the context of multidimensional definitions of frailty. Furthermore, we report novel associations between this allele and the memory domain of FI and the psychological domain of TFI, that includes memory problems on its components. Given that frailty burden has been shown to modify the AD clinical presentation, it is likely that rs7038172 C allele may accelerate the transition of AD or frailty to dementia Overall, our study corroborates the role of the 9p21-23 region in frailty development and draw potential links with AD pathology.

Plasma GSH levels and Alzheimer's disease. A prospective approach.: Results from the HELIAD study.

BACKGROUND: Potential links between oxidative stress and the pathophysiology of Alzheimer's disease (AD) have been reported in the existing literature. Biological markers of oxidative stress, such as the reduced form of glutathione (GSH), may have a potential role as predictive biomarkers for AD development. The aim of the present study was to explore the longitudinal associations between plasma GSH and the risk of developing AD or cognitive decline, in a sample of community-dwelling, non-demented older adults. METHODS: Participants from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present prospective study. The sample used in the analyses consisted of 391 non-demented individuals over the age of 64 (mean age = 73.85 years; SD = 5.06), with available baseline GSH measurements and longitudinal follow-up. Plasma GSH was treated both as a continuous variable and as tertiles in our analyses. Cox proportional hazards models were used to evaluate the hazard ratio (HR) for AD incidence as a function of baseline plasma GSH. Generalized estimating equations (GEE) models were deployed to explore the associations between baseline plasma GSH and the rate of change of performance scores on individual cognitive domains over time. Models were adjusted for age, years of education and sex. Supplementary exploratory models were also adjusted for mild cognitive impairment (MCI) at baseline, risk for malnutrition, physical activity and adherence to the Mediterranean dietary pattern. RESULTS: A total of 24 incident AD cases occurred during a mean (SD) of 2.99 (0.92) years of follow-up. Individuals in the highest GSH tertile group (highest baseline plasma GSH values) had a 70.1% lower risk for development of AD, compared to those in the lowest one [HR = 0.299 (0.093-0.959); p = 0.042], and also demonstrated a slower rate of decline of their executive functioning over time (5.2% of a standard deviation less decline in the executive composite score for each additional year of follow-up; p = 0.028). The test for trend was also significant suggesting a potential dose-response relationship. CONCLUSION: In the present study, higher baseline plasma GSH levels were associated with a decreased risk of developing AD and with a better preservation of executive functioning longitudinally.

Facial palsy caused by an intrameatal metastatic disease - Reconstruction with an autologous sural nerve graft.

Dysfunction of the facial nerve is frequently attributed to inflammation, followed by traumatic injury. Knowledge of the complex anatomical course of the facial nerve is critical to localize the site of pathology and for successful management. The multiplicity of etiologies and its complex anatomy often make facial paralysis a diagnostic challenge. Neoplasms are a fairly rare cause of peripheral facial palsy, and are frequently overlooked in search of the more frequent traumatic or inflammatory etiologies of facial paralysis. Isolated metastatic lesions to the cerebellopontine angle (CPA) and internal auditory canal (IAC) are extremely rare. Their accurate diagnosis is difficult, since they share common clinical and radiological characteristics with vestibular schwannomas. We report a case of a 63-year-old female with a rapidly progressive left-sided hearing loss and complete facial palsy. Magnetic resonance imaging revealed a left intrameatal lesion. A provisional diagnosis of intracanalicular schwannoma or meningioma was made, although the possibility of metastasis due to her rapid neurological deterioration was considered. The patient underwent a translabyrinthine complete removal of the tumor followed by facial nerve reconstruction. The final histopathological findings revealed a metastatic breast adenocarcinoma. To our knowledge only seven prior cases of an isolated metastatic CPA lesion have been reported. In patients without a known malignancy, a rapid progression of hearing loss, disequilibrium, and facial palsy might be the first sign of a metastatic CPA lesion.

Black holes and high levels of neurofilaments in glial fibrillary acidic protein - astrocytopathy: a case report.

BACKGROUND AND PURPOSE: Glial fibrillary acidic protein (GFAP) is an intracellular protein of the astrocytic cytoskeleton. Recently, autoantibodies to GFAP detected by cell-based assay in cerebrospinal fluid (CSF) or serum have been implicated in cerebral astrocytopathy, presenting predominantly with autoimmune meningoencephalomyelitis. However, the phenotypic spectrum, prognosis and therapeutics of this new entity remain to be elucidated. METHODS: Herein, we report radiological, CSF and serological findings during disease exacerbation and remission, from a patient with autoimmune GFAP astrocytopathy, presenting as an immunotherapy responsive GFAP IgG-associated meningoencephalomyelitis. RESULTS: Brain and spine magnetic resonance imaging revealed meningeal enhancement, T2 hyperintensities, black holes, significant sulci widening and spinal atrophy. In addition, high levels of neurofilaments (NfL) and GFAP were also identified during disease exacerbation, consistent with the appearance of the black holes. CONCLUSIONS: To date, black holes and atrophy have never been reported before in autoimmune GFAP astrocytopathy. These findings, combined with the high levels of GFAP and NfL, suggest the existence of an underlying neurodegenerative mechanism in addition to the known inflammatory response. Further studies are needed to elucidate the pathomechanism of GFAP-astrocytopathies.

Prevalence and Risk Factors of Frailty in a Community-Dwelling Population: The HELIAD Study.

Objective: To estimate the prevalence of frailty using five different instruments in a cohort of older adults and explore the association between frailty and various risk factors. Method: 1,867 participants aged 65 years and above were included in the current retrospective cross-sectional study. Frailty was operationalized according to the Fried definition, the FRAIL Scale, the Frailty Index (FI), the Tilburg Frailty Indicator (TFI), and the Groningen Frailty Index (GFI). We explored the role of various frailty risk factors using logistic regression analyses. Results: The prevalence of frailty varied depending on the definition used (Fried definition = 4.1%, FRAIL Scale = 1.5%, FI = 19.7%, TFI = 24.5%, and GFI = 30.2%). The only risk factors consistently associated with frailty irrespectively of definition were education and age. Conclusion: The frailty prevalence reported in our study is similar or lower to that reported in other population studies. Qualitative differences between frailty definitions were observed.

Assessing functional status using the IADL-extended scale: results from the HELIAD study.

OBJECTIVES: Instrumental activities of daily living (IADL) have been operationalized as exhibiting a greater level of complexity than basic ADL. In the same way, incorporating more advanced ADLs may increase the sensitivity of functional measures to identify cognitive changes that may precede IADL impairment. Towards this direction, the IADL-extended scale (IADL-x) consists of four IADL tasks and five advanced ADLs (leisure time activities). DESIGN: Retrospective, cross-sectional study. SETTING: Athens and Larissa, Greece. PARTICIPANTS: 1,864 community-dwelling men and women aged over 64. MEASUREMENTS: We employed both the IADL-x and IADL scales to assess functional status among all the participants. Diagnoses were assigned dividing the population of our study into three groups: cognitively normal (CN), mild cognitive impairment (MCI) and dementia patients. Neuropsychological evaluation was stratified in five cognitive domains: memory, language, attention-speed, executive functioning and visuospatial perception. Z scores for each cognitive domain as well as a composite z score were constructed. Models were controlled for age, sex, education and depression. RESULTS: In both IADL-x and IADL scales dementia patients reported the most functional difficulties and CN participants the fewest, with MCI placed in between. When we restricted the analyses to the CN population, lower IADL-x score was associated with worse cognitive performance. This association was not observed when using the original IADL scale. CONCLUSION: There is strong evidence that the endorsement of more advanced IADLs in functional scales may be useful in detecting cognitive differences within the normal spectrum.

Long-term effects of prolonged-release fampridine in cognitive function, fatigue, mood and quality of life of MS patients: The IGNITE study.

BACKGROUND: Studies have reported conflicting results regarding the potential benefit of prolonged release (PR) fampridine in other domains besides walking. Moreover, only a small number of studies have explored long- term effects of PR fampridine. The aim of this study was to assess cognitive function, quality of life, mood and fatigue in MS patients treated with fampridine after 6 and 12 months of treatment. METHODS: IGNITE was an observational, open label study. Subjects were examined with the timed 25-ft walk (T25FW) and the BICAMS battery and were asked to complete the Multiple Sclerosis Impact Scale (MSIS-29), Modified Fatigue Impact Scale (MFIS), Beck Depression Inventory-II (BDI-II) and MS International Quality-of-Life questionnaire (MUSIQOL) at baseline and at weeks 24 and 48. Patients were sub-grouped into responders (n:40) and non-responders (n:20) according to T25FW performance after 2 weeks on treatment. RESULTS: After 6 months, statistically significant improvement was observed on T25FW (p < .001), SDMT (p < .001) and MSIS29 (p < .001), for responders. After 1 year on treatment, statistically significant improvement was observed in T25FW (p < .001), MSIS29 (p = .004), SDMT (p < .001) and MUSIQOL (p = .03) for responders. There were no statistically significant improvements for the non-responders. CONCLUSIONS: PR Fampridine may have a beneficial effect on information processing speed though not on memory. Study data provide some evidence that fampridine treatment may reduce the impact of MS on daily activities and improve quality of life but has no effect on subjective fatigue and mood.

The contribution of genetic variants of SLC2A1 gene in T2DM and T2DM-nephropathy: association study and meta-analysis.

An association study was conducted to investigate the relation between 14 variants of glucose transporter 1 gene (SLC2A1) and the risk of type 2 diabetes (T2DM) leading to nephropathy. We also performed a meta-analysis of 11 studies investigating association between diabetic nephropathy (DN) and SLC2A1 variants. The cohort included 197 cases (T2DM with nephropathy), 155 diseased controls (T2DM without nephropathy) and 246 healthy controls. The association of variants with disease progression was tested using generalized odds ratio (ORG). The risk of type 2 diabetes leading to nephropathy was estimated by the OR of additive and co-dominant models. The mode of inheritance was assessed using the degree of dominance index (h-index). We synthesized results of 11 studies examining association between 5 SLC2A1 variants and DN. ORG was used to assess the association between variants and DN using random effects models. Significant results were derived for co-dominant model of rs12407920 [OR = 2.01 (1.17-3.45)], rs841847 [OR = 1.73 (1.17-2.56)] and rs841853 [OR = 1.74 (1.18-2.55)] and for additive model of rs3729548 [OR = 0.52 (0.29-0.90)]. The mode of inheritance for rs12407920, rs841847 and rs841853 was 'dominance of each minor allele' and for rs3729548 'non-dominance'. Frequency of one haplotype (C-G-G-A-T-C-C-T-G-T-C-C-A-G) differed significantly between cases and healthy controls [p = .014]. Regarding meta-analysis, rs841853 contributed to an increased risk of DN [(ORG = 1.43 (1.09-1.88); ORG = 1.58 (1.01-2.48)] between diseased controls versus cases and healthy controls versus cases, respectively. Further studies confirm the association of rs12407920, rs841847, rs841853, as well as rs3729548 and the risk of T2DM leading to nephropathy.

History of induced abortions and frailty in older Greek women: results from the HELIAD study.

PURPOSE: Women are almost twice as likely as men to develop frailty and early-traumatic experiences related to reproduction may have a role to play. The purpose of this study was to investigate the association between a history of induced abortions and risk of frailty. METHODS: 1062 women aged ≥ 65 years from the HELIAD study were included in the present cross-sectional study. Frailty was assessed by frailty index and Fried definitions. The history of abortion and of other reproductive experiences (age onset of menstruation, age of menopause, number of offspring, and number of miscarriages) was obtained by all participants. Logistic and linear regression analyses were performed to examine whether the number of abortions was related to frailty. RESULTS: When frailty was defined with frailty index, women with 1 or 2 abortions had 1.7 higher risk of frailty compared to women with no history of abortions, while those with more than 3 abortions had more than a twofold higher risk of frailty. Two supplementary analyses excluding women with surgical operations' history and women with dementia revealed similar results. When frailty was defined with Fried definition, the analysis was marginally significant when abortion was inserted as a categorical variable. Women with more than 3 abortions showed 2.4 higher risk of frailty compared to women with no history of abortion. CONCLUSION: The number of induced abortions was associated with moderate higher odds of frailty, when frailty was defined according to frailty index. A similar trend was revealed in the model with Fried definition after trichotomization of abortions.

Dataset on the associations between sleep quality/duration and cognitive performance in cognitively healthy older adults.

In the present data, we provide the details of the cross-sectional study examining the associations between sleep quality/sleep duration and cognitive performance. Data are from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A total of 1484 older adults (65 y.o. or older) took part in the study. Sleep measurements were drawn from the sleep scale of the Medical Outcomes Study (MOS). Cognition was used as a z-score drawn by different tests. The domains examined were: executive function, visuo-spatial ability, language, attention- speed of processing, as well as the composite z-score of all the cognitive domains (including memory). Linear regression models were conducted to investigate the associations between sleep quality and cognition, and sleep duration and cognition as well. We also conducted linear regression analyses for the associations between sleep quality/duration and cognitive domains/composite cognitive score based on the status of the Apolipoprotein E-ε4 (ApoE-ε4) genotype. Analyses were performed excluding both the demented and the Mild Cognitive Impairment (MCI) participants. Adjustments conducted for multiple covariates. For further analyses and enhanced discussion, see original article: "Sleep quality and duration in relation to memory in the elderly: initial results from the Hellenic Longitudinal Investigation of Aging and Diet" by Tsapanou et al. [1].

Viruses and endogenous retroviruses in multiple sclerosis: From correlation to causation.

Multiple sclerosis is an immune-mediated disease with an environmental component. According to a long-standing but unproven hypothesis dating to initial descriptions of multiple sclerosis (MS) at the end of the 19th century, viruses are either directly or indirectly implicated in MS pathogenesis. Whether viruses in MS are principally causal or simply contributory remains to be proven, but many viruses or viral elements-predominantly Epstein-Barr virus, human endogenous retroviruses (HERVs) and human herpesvirus 6 (HHV-6) but also less common viruses such as Saffold and measles viruses-are associated with MS. Here, we present an up-to-date and comprehensive review of the main candidate viruses implicated in MS pathogenesis and summarize how these viruses might cause or lead to the hallmark demyelinating and inflammatory lesions of MS. We review data from epidemiological, animal and in vitro studies and in doing so offer a transdisciplinary approach to the topic. We argue that it is crucially important not to interpret "absence of evidence" as "evidence of absence" and that future studies need to focus on distinguishing correlative from causative associations. Progress in the MS-virus field is expected to arise from an increasing body of knowledge on the interplay between viruses and HERVs in MS. Such interactions suggest common HERV-mediated pathways downstream of viral infection that cause both neuroinflammation and neurodegeneration. We also comment on the limitations of existing studies and provide future research directions for the field.

Sleep quality and duration in relation to memory in the elderly: Initial results from the Hellenic Longitudinal Investigation of Aging and Diet.

BACKGROUND: Sleep is crucial for cognition, particularly for memory, given its complex association with neurodegenerative processes. The aim of the present study was to examine the association between sleep quality as well as sleep duration and memory performance in a Greek elderly population. SETTING: Cross-sectional design in the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD), a population representative study of Greek elderly (65years or older). METHODS: Data from 1589 participants free of sleep medication were included. Sleep quality was estimated by using the Sleep Scale from the Medical Outcomes Study. An extensive neuropsychological assessment examining memory was administered to each participant. Linear regression analyses were used to examine whether sleep quality (higher score, poor quality) and/or sleep duration were associated with memory expressed in the form of a z-score. Age, sex, education, and body mass index were included as covariates. The main analyses were conducted first on the total sample, then with the exclusion of demented participants, and finally with the exclusion of both demented and participants with Mild Cognitive Impairment (MCI). We then conducted further analyses on the non-demented, non-MCI group, initially stratified by Apolipoprotein E-ε4 gene. We further examined the role of co-morbidities, as well as the association between sleep duration groups and memory. We also explored any interaction effect between sex and sleep quality/duration on memory. We then examined the associations between components of sleep measures and memory scores. Lastly, we examined the associations between sleep quality/duration and verbal/non-verbal memory separately. RESULTS: In the total sample, we noted significant associations between sleep duration and memory (B=-0.001, p≤0.0001), but not for sleep quality and memory (B=-0.038, p=0.121). After excluding the demented participants, the associations were significant for: sleep quality and memory (B=-0.054, p=0.023), and sleep duration and memory (B=-0.001, p≤0.0001). After excluding both the MCI and the demented subjects, the associations between sleep quality and memory (B=-0.065, p=0.006), and sleep duration and memory (B=-0.001, p=0.003) were still significant. The association between the sleep duration groups and memory function was also significant, such that poor memory performance was associated with the longer sleep duration group. The results remained significant even after controlling for the co-morbidities, as well as after adding in the model anxiety and depression as covariates. Associations between sleep quality and memory, and sleep duration and memory were present in the ApoE-ε4 non-carriers. The individual sleep questions that were probably shown to be driving the associations between sleep and memory were: time to fall asleep, sleep not quiet, getting enough sleep to feel rested upon waking in the morning, and getting the amount of sleep needed. Sleep duration was associated with both verbal and non-verbal memory, while sleep quality was only associated with verbal memory. CONCLUSION: Poor sleep quality and longer sleep duration were linked to low memory performance, independent of demographic and clinical factors, in a large sample of cognitively healthy older Greek adults. Other parameters than sleep and memory measurements could play an important role on the association. Levels of melatonin, or circadian rhythms dysregulation might play a crucial role in the above associations.

Wound ballistics 101: the mechanisms of soft tissue wounding by bullets.

PURPOSE: The mechanisms of soft tissue injury by bullets are reviewed, in the belief that the current incidence of firearm injuries in many urban areas necessitates an understanding of wound ballistics on the part of trauma surgeons who may not be familiar with the wounding factors involved. METHODS: Review of the literature, with technical information obtained from appropriate non-medical texts. RESULTS: Despite numerous publications concerning the treatment of gunshot wounds, relatively few papers contain details on the mechanisms of ballistic trauma, with the main body of evidence derived from previous laboratory and animal studies which have only recently been systematically appraised. These studies have shown that in rifle injuries the main wound tract is surrounded by an area of damaged tissue as a result of the temporary cavitation induced once the bullet becomes destabilized or deformed. On the other hand, the more commonly encountered non-deforming handgun bullets cause damage limited to the bullet's path, mainly as a result of localized crush injury. CONCLUSIONS: The bullet's construction and ballistic behavior within tissue determine to what extent the previously overestimated velocity factor may influence wound severity. The damage produced from temporary cavitation depends on the tensile properties of the tissues involved, and in high-energy injuries may lead to progressive muscle tissue necrosis. Therefore, the term "high-energy" should be reserved for those injuries with substantial tissue damage extending beyond the visible wound tract.