Josephsengriffin4555

Background The role of cognitive reserve (CR) to explain individual differences in cognitive functioning is unclear in memory clinic patients. Objective To examine the cross-sectional effect of CR on cognition in relation to levels of neurodegeneration in a large elderly single-center memory clinic population. Methods We included patients with subjective cognitive impairment (SCI, n = 481), mild cognitive impairment (MCI, n = 628) or Alzheimer's disease (AD, n = 1,099). Education was used as proxy for CR and visually rated medial temporal lobe atrophy (MTA) on CT was used as parameter of neurodegeneration. Relations between CR, cognition, and MTA were analyzed with multiple linear regression adjusted for age, sex, and cerebral atrophy. In addition, we examined if education affects the relation between MTA and cognition using an interaction variable. Results Education was significantly related to all measures of cognition including subtests with an explained variance of education as a determinant of cognition of 11%. More highly educated patients had more advanced levels of MTA at the same level of cognition. All these results were stronger or only present in demented compared to non-demented patients but appeared no longer significant in those with lowest overall cognition. The interaction effect was significant indicating that with more advanced MTA, less cognitive decline was shown in higher educated patients. Conclusion Education is a very strong determinant of cognition in an elderly memory clinic population. The positive effect of education was stronger in demented than in non-demented patients but disappeared in those with the lowest cognitive scores indicating a "window of CR benefit".Background A complex set of interactions between biological, genetic, and environmental factors likely underlies the development of Alzheimer's disease (AD). Identifying which of these factors is most associated with AD is important for early diagnosis and treatment. Objective We sought to examine genetic risk and structural brain volume on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD. Methods 686 adults (55-91 years old) completed a 3T MRI scan, baseline cognitive assessments, and biospecimen collection through the Alzheimer's Disease Neuroimaging Initiative. Hierarchical linear regression analyses examined main and interaction effects of medial temporal lobe (MTL) volume and polygenic hazard score (PHS), indicating genetic risk for AD, on a validated episodic memory composite score. Results Genetic risk moderated the relationship between MTL volume and memory, such that individuals with high PHS and lower hippocampal and entorhinal volume had lower memory composite scores [ΔF (1,677) = 4.057, p = 0.044, ΔR2 = 0.002]. Further analyses showed this effect was driven by the left hippocampus [ΔF(1,677) = 5.256, p = 0.022, ΔR2 = 0.003] and right entorhinal cortex [ΔF (1,677) = 6.078, p = 0.014, ΔR2 = 0.003]. Conclusions Among those with high genetic risk for AD, lower volume was associated with poorer memory. Results suggest that the interaction between AD genetic risk and MTL volume increases the likelihood for memory impairment among older adults. Results from this study suggest that genetic risk and brain volume should be considered key factors in tracking cognitive decline.Background Neuroinflammatory cytokines can play a pivotal role in Alzheimer's disease (AD) contributing to the evolution of degenerative processes. Objective We aimed at evaluating the levels of cerebrospinal fluid (CSF) inflammatory cytokines, chemokines, and growth factors in subjects with diagnosis of amnestic mild cognitive impairment and mild AD. Methods We evaluated CSF contents of inflammatory cytokines in 66 patients divided according to the NIA-AA research framework and the APOE genotype. CSF of a group of cognitively unimpaired individuals (n = 23) was evaluated as control. All patients were evaluated for 24 months using Mini-Mental State Examination (MMSE). Results We found significant increased levels of IL-4, IL-6, IL-8, and G-CSF in the CSF of A+/T-APOE4 carriers, respect to A+/T-patients homozygous for APOE3, respect to A+/T+ patients, regardless the APOE status, and respect to controls. Over a period of 24 months, A+/T-APOE4 carriers, with increased levels of cytokines, showed a preserved cognitive evaluation when compared to the other subgroups of patients (delta MMSE at 24 months respect to baseline 0.10±0.35; p less then 0.05). Conclusion Our data suggest that during early phases of AD, in APOE4 carriers, Aβ pathology likely induces a specific cytokines pattern synthesis associated to cognitive preservation. These data highlight the different role that neuroinflammation can play in AD pathology based on the presence of specific CSF biomarkers and on the APOE status.Background Altered calcium homeostasis is hypothesized to underlie Alzheimer's disease (AD). However, it remains unclear whether serum calcium levels are genetically associated with AD risk. Objective To develop effective therapies, we should establish the causal link between serum calcium levels and AD. Methods Here, we performed a Mendelian randomization study to investigate the causal association of increased serum calcium levels with AD risk using the genetic variants from a large-scale serum calcium genome-wide association study (GWAS) dataset (61,079 individuals of European descent) and a large-scale AD GWAS dataset (54,162 individuals including 17,008 AD cases and 37,154 controls of European descent). Here, we selected the inverse-variance weighted (IVW) as the main analysis method. Meanwhile, we selected other three sensitivity analysis methods to examine the robustness of the IVW estimate. Results IVW analysis showed that the increased serum calcium level (per 1 standard deviation (SD) increase 0.5 mg/dL) was significantly associated with a reduced AD risk (OR = 0.57, 95% CI 0.35-0.95, p = 0.031). learn more Meanwhile, all the estimates from other sensitivity analysis methods were consistent with the IVW estimate in terms of direction and magnitude. Conclusion In summary, we provided evidence that increased serum calcium levels could reduce the risk of AD. Meanwhile, randomized controlled study should be conducted to clarify whether diet calcium intake or calcium supplement, or both could reduce the risk of AD.Care home residents with dementia often have accompanying agitation. We investigated agitation's course at 5 time-points in 1,424 people with dementia over 16 months in 86 English care homes. We categorized baseline agitation symptoms on the Cohen-Mansfield Agitation Inventory (CMAI) into none (CMAI = 29; 15%), subclinical (CMAI = 30-45; 45%), or clinically-significant (CMAI > 45; 40%). 88% of those with no agitation at baseline remained free of clinically-significant agitation at all follow-ups. Seventy percent of those exhibiting clinically-significant agitation at baseline had clinically-significant agitation at some follow-ups. Over a 16-month observation period, this study finds many care home residents with dementia never develop clinically significant agitation and interventions should be for treatment not prevention.Background While sex differences in incidence of Alzheimer's disease (AD) and potential explanations have received considerable attention, less attention has been paid to possible sex differences in genetic risk for AD. Objective We examined sex differences in genetic and environmental influences on disease risk and age at onset for All Dementia, AD Only, and Non-AD Dementia. Methods Twin pairs were drawn from the Swedish Twin Registry. All Dementia analysis included 9,467 pairs; AD only, 8,696 pairs; and non-AD dementia, 8,195 pairs. APOE analyses included 1,923 individual twins with measured ɛ4 alleles. Dementia diagnoses were based on clinical workup and national health registry linkage. Results Although within-pair correlations for All Dementia and AD Only were higher for women than for men, sex differences did not statistically differ for genetic or environmental etiology of All Dementia, AD Only, and Non-AD dementia. Similar results were observed when looking at specific genetic effects (APOEɛ4). Co-twin control analyses indicated that among twin pairs discordant for dementia, female twins without dementia had approximately 40% greater risk of developing dementia, compared with their male counterparts, in the 2-5 years following the first twin's diagnosis. Conclusion For All Dementia, AD Only, and Non-AD Dementia, genetic influences could be equated across sex. Co-twin analyses, however, suggest greater risk to female than to male co-twins of dementia cases even though sex differences in either genetic or shared environmental influences on the risk of dementia could not be differentiated.Background Both pain interference and depressive symptoms have certain effects on dementia, and these are reciprocally related. However, comorbid effects of pain interference and depressive symptoms on dementia have not been examined in detail. Objective This longitudinal study aimed to examine the combined effects of pain interference and depressive symptoms on the incidence of dementia in community-dwelling elderly individuals. Methods This prospective cohort study with a 36-month follow-up period included 4,326 community-dwelling elderly individuals without dementia at baseline. Pain interference and depressive symptoms were assessed for every participant at baseline. We collected medical records in the Japanese public health insurance system to identify the incidence of dementia for 36 months. Results The incidence rates of dementia during the follow-up period in the control, pain-interference, depressive-symptoms, and comorbid group were 3.2%, 6.2%, 7.9%, and 11.3%, respectively. A Cox regression analysis showed that the hazard ratios for the incidence of dementia were 1.85 (95% CI 1.13-3.03) in the pain interference group, 1.87 (95% CI 1.27-2.76) in the depressive symptoms group, and 2.20 (95% CI 1.26-3.84) in the comorbid group, after adjusting for covariates. Conclusion The coexistence of pain interference and depressive symptoms had a greater effect on the incidence of dementia than either condition alone in community-dwelling elderly individuals. Pain interference and depressive symptoms are known as common comorbid conditions and often form a negative cycle that accelerates the worsening of the individual symptoms of both. Thus, the comorbidity of these conditions may require monitoring for the prevention of dementia.Some months ago, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, and spread rapidly around the world. Some states, such as the Netherlands, Germany, Great Britain, Sweden and the USA initially focused on keeping the restrictions for economy and society as low as possible. The responsible authorities were of the opinion - and still are e.g. in Sweden - that it is sufficient enough to protect particularly vulnerable persons such as the elderly or people with pre-existing conditions. The idea behind this is that as soon as 60 to 70 percent of the population is infected with a pathogen, a so-called "herd immunity" has developed. However, the increasing numbers of deaths and modelling studies showed the expected overload of the hospitals. Therefore, most countries decided for a temporary lockdown with the exception of Sweden.Based on the number of the total population, three times more people died from COVID-19 in Sweden (2679 deaths per 10 million inhabitants) compared to Germany (6848 deaths per 80 million inhabitants).