Subjective memory complaints predict baseline but not future cognitive function over three years: results from the Western Australia Memory Study.

ABSTRACTBackground:This study investigated the characteristics of subjective memory complaints (SMCs) and their association with current and future cognitive functions. METHODS: A cohort of 209 community-dwelling individuals without dementia aged 47-90 years old was recruited for this 3-year study. Participants underwent neuropsychological and clinical assessments annually. Participants were divided into SMCs and non-memory complainers (NMCs) using a single question at baseline and a memory complaints questionnaire following baseline, to evaluate differential patterns of complaints. In addition, comprehensive assessment of memory complaints was undertaken to evaluate whether severity and consistency of complaints differentially predicted cognitive function. RESULTS: SMC and NMC individuals were significantly different on various features of SMCs. Greater overall severity (but not consistency) of complaints was significantly associated with current and future cognitive functioning. CONCLUSIONS: SMC individuals present distinctive features of memory complaints as compared to NMCs. Further, the severity of complaints was a significant predictor of future cognition. However, SMC did not significantly predict change over time in this sample. These findings warrant further research into the specific features of SMCs that may portend subsequent neuropathological and cognitive changes when screening individuals at increased future risk of dementia.

Serum high-density lipoprotein is associated with better cognitive function in a cross-sectional study of aging women.

Purpose/Aim of the study: Poor cardiovascular health, including obesity and altered lipid profiles at mid-life, are linked to increased risk of Alzheimer's disease (AD). The biological mechanisms linking cardiovascular health and cognitive function are unclear though are likely to be multifactorial. This study examined the association between various lipoproteins and cognitive functioning in ageing women. MATERIALS AND METHODS: We investigated the relationship between readily available biomarkers (i.e. serum lipoprotein) and cognitive decline in domains associated with increased risk of AD (e.g. episodic verbal memory performance and subjective memory complaint). We report cross-sectional data investigating the relationship between serum total cholesterol, triglycerides, high-density lipoprotein (HDL-C) and low-density lipoprotein with verbal memory and learning ability in 130 women with and without memory complaints (n = 71 and 59, respectively) drawn from a study investigating cognitively healthy Western Australians (average age 62.5 years old). RESULTS: After statistical modelling that controlled for the effects of age, depression and apolipoprotein E genotype, HDL-C was significantly associated with better verbal learning and memory performance, specifically short and long delay-free recalls (F = 3.062; p < .05 and F = 3.2670; p < .05, respectively). CONCLUSION: Our cross-sectional findings suggest that the positive effect of HDL-C on verbal memory may be present much earlier than previously reported and provide further support for the role of HDL-C in healthy brain ageing. Further exploration of the protective effect of HDL-C on cognitive function in ageing is warranted through follow-up, longitudinal studies.

Direct exposure of guinea pig CNS to human luteinizing hormone increases cerebrospinal fluid and cerebral beta amyloid levels.

BACKGROUND/AIMS: Luteinizing hormone (LH) has been shown to alter the metabolism of beta amyloid (Aß), a key protein in Alzheimer's disease (AD) pathogenesis. While LH and components required for LH receptor signalling are present in the brain, their role in the CNS remains unclear. In vitro, LH has been shown to facilitate neurosteroid production and alter Aß metabolism. However, whether LH can directly modulate cerebral Aß levels in vivo has not previously been studied. In this study, we investigated the effect of chronic administration of LH to the guinea pig CNS on cerebral Aß levels. METHODS: Gonadectomised male animals were administered, via cortical placement, either placebo or LH slow-release pellets. At 14 and 28 days after treatment, animals were sacrificed. Brain, plasma and CSF were collected and Aß levels measured via ELISA. Levels of the Aß precursor protein (APP) and the neurosteroidogenic enzyme cytochrome P450 side-chain cleavage enzyme (P450scc) were also assayed. RESULTS: An increase in CSF Aß40 levels was observed 28 days following treatment. These CSF data also reflected changes in Aß40 levels observed in brain homogenates. No change was observed in plasma Aß40 levels but APP and its C-terminal fragments (APP-CTF) were significantly increased in response to LH exposure. Protein expression of P450scc was increased after 28 days of LH exposure, suggesting activation of the LH receptor. CONCLUSION: These data indicate that direct exposure of guinea pig CNS to LH results in altered brain Aß levels, perhaps due to altered APP expression/metabolism.

The relationship between memory complaints, perceived quality of life and mental health in apolipoprotein Eepsilon4 carriers and non-carriers.

Apolipoprotein E epsilon4 (APOE-epsilon4) is a major genetic risk factor for Alzheimer's disease. In this study, we addressed the question of whether possession of the APOE-epsilon4 allele results in adverse effects on perceived health-related quality of life (HRQL) and on symptoms of depression and anxiety in people with subjective memory complaints (SMC). 138 healthy, community-dwelling elderly volunteers, aged 52 to 85, were assessed for HRQL, depression, and anxiety. The participants were classified as i) APOE-epsilon4 carriers or ii) non-carriers with a) SMC or b) without memory complaints. The possible interactions of APOE genotype, gender, and SMC on HRQL, depression, and anxiety were investigated statistically. SMC was significantly associated with poorer outcomes on measures of depression, trait anxiety, and mental health. APOE-epsilon4 carriers did not significantly differ from non-carriers on HRQL, depression, and anxiety. However, significant interaction was found between APOE-epsilon4 genotype and SMC on depression. These findings are important from a health perspective and suggest that memory complaints are associated with markers of mental health and quality of life that are independent of possession of the APOE-epsilon4 allele, despite the importance of this polymorphism in the risk of AD and other health problems.

Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer's disease.

BACKGROUND: Inflammatory changes are a prominent feature of brains affected by Alzheimer's disease (AD). Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins and TNFA, which are associated with AD. The gene coding for HLA-B associated transcript 1 (BAT1) lies adjacent to TNFA in the central major histocompatibility complex (MHC). BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current study TNFA and BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases. METHODS: Genotyping was performed for polymorphisms at positions -850 and -308 in the proximal promoter of TNFA and position -22 in the promoter of BAT1. These were investigated singly or in haplotypic association in a cohort of Australian AD patients with AD stratified on the basis of their APOE epsilon4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases. RESULTS: APOE epsilon4 was associated with an independent increase in risk for AD in individuals with TNFA -850*2, while carriage of BAT1 -22*2 reduced the risk for AD, independent of APOE epsilon4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels of BAT1 mRNA in frontal cortex of AD cases. CONCLUSION: These findings lend support to the application of TNFA and BAT1 polymorphisms in early diagnosis or risk assessment strategies for AD and suggest a potential role for BAT1 in the regulation of inflammatory reactions in AD pathology.

Distinct effects of testosterone on plasma and cerebrospinal fluid amyloid-beta levels.

The effect of testosterone on the levels of the Alzheimer's disease amyloid-beta peptide (Abeta) was investigated in guinea pigs. Castrated guinea pigs (GPX) were administered testosterone at two different dosages, following which plasma and cerebrospinal fluid (CSF) Abeta_{40} levels were measured. Plasma Abeta_{40} levels were reduced in GPX in the early stages of low-dose testosterone treatment, whereas CSF Abeta_{40} levels were only reduced by the time circulating testosterone had returned to untreated GPX levels. The supraphysiological testosterone dose did not reduce CSF Abeta_{40} levels significantly until circulating testosterone was back to uncastrated levels, whereas plasma Abeta_{40} levels significantly increased over time in these animals. These results indicate that the extent of testosterone-induced changes to Abeta_{40} levels and their response rates depend on both the tissue examined and testosterone dosage.

Bone mineral density, adiposity, and cognitive functions.

Cognitive decline and dementia due to Alzheimer's disease (AD) have been associated with genetic, lifestyle, and environmental factors. A number of potentially modifiable risk factors should be taken into account when preventive or ameliorative interventions targeting dementia and its preclinical stages are investigated. Bone mineral density (BMD) and body composition are two such potentially modifiable risk factors, and their association with cognitive decline was investigated in this study. 164 participants, aged 34-87 years old (62.78 ± 9.27), were recruited for this longitudinal study and underwent cognitive and clinical examinations at baseline and after 3 years. Blood samples were collected for apolipoprotein E (APOE) genotyping and dual energy x-ray absorptiometry (DXA) was conducted at the same day as cognitive assessment. Using hierarchical regression analysis, we found that BMD and lean body mass, as measured using DXA were significant predictors of episodic memory. Age, gender, APOE status, and premorbid IQ were controlled for. Specifically, the List A learning from California Verbal Learning Test was significantly associated with BMD and lean mass both at baseline and at follow up assessment. Our findings indicate that there is a significant association between BMD and lean body mass and episodic verbal learning. While the involvement of modifiable lifestyle factors in human cognitive function has been examined in different studies, there is a need for further research to understand the potential underlying mechanisms.

Association between the presenilin-1 mutation Glu318Gly and complaints of memory impairment.

Presenilin-1 mutations account for nearly 50% of all early-onset familial cases of Alzheimer's disease. Most of these mutations are completely penetrant, although the recently described Glu318Gly substitution seems to have only partial penetrance. These findings suggest that the Glu318Gly mutation may work as a genetic risk factor for Alzheimer's disease. We designed the present study to investigate the frequency of this mutation among non-demented volunteers with subjective memory impairment (n = 58) and controls (n = 66). Four (6.8%) subjects with complaints of memory problems, but no controls, carried this mutation. The presence of the Glu318Gly mutation was associated with significantly lower cognitive performance when compared to controls (P = 0.011). However, there was no significant association between the presence of the mutation and the cognitive performance of individuals within the memory complainers group. Follow-up studies should clarify whether the Glu318Gly mutation increases the risk of cognitive decline in later life.

Functional effects of genetic polymorphism in inflammatory genes in subjective memory complainers.

A number of genetic risk factors have been identified for Alzheimer's disease (AD) including genes involved in the inflammatory response (interleukin 1A, [IL-1α (-889)], interleukin 1B (IL-1ß [+3953]), and tumor necrosis factor (TNF [-308 and -850]). We investigated the prevalence and functional consequences (baseline cognitive performance, plasma cytokine levels) of possession of these putative genetic risk factors within a group of subjective memory complainers (SMC, n = 226) and age and sex matched noncomplainers (NMC, n = 167). We observed no effect of any of the genetic factors investigated on cognitive performance. Further, there was no difference in the frequency of the disease-associated alleles, or cytokine levels between subjective memory complainers and noncomplainer participants. There was no relationship between TNF polymorphisms and TNF levels. There was a significant increase in plasma IL-1ß levels in those homozygous for the disease-associated allele (i.e., IL-1ß +3953 TT). Follow-up longitudinal assessments on this cohort will provide insight as to how these polymorphisms may affect the risk of cognitive decline over time.

Association of cardiovascular factors and Alzheimer's disease plasma amyloid-beta protein in subjective memory complainers.

A strong link is indicated between cardiovascular disease (CVD) and risk for developing Alzheimer's disease (AD), which may be exacerbated by the major AD genetic risk factor apolipoprotein Eepsilon4 (APOEepsilon4). Since subjective memory complaint (SMC) may potentially be an early indicator for cognitive decline, we examined CVD risk factors in a cohort of SMC. As amyloid-beta (Abeta) is considered to play a central role in AD, we hypothesized that the CVD risk profile (increased LDL, reduced HDL, and increased body fat) would be associated with plasma Abeta levels. We explored this in 198 individuals with and without SMC (average age = 63 years). Correlations between Abeta40 and HDL were observed, which were stronger in non-APOEepsilon4 carriers (rho = -0.315, p < 0.001) and in SMC (rho = -0.322, p = 0.01). There was no relationship between percentage body fat and Abeta40 in this cohort. Age and HDL remained predictive for plasma Abeta40 using multivariate regression analysis. We report a novel negative association between HDL and Abeta, which if demonstrated to be causal has implications for the development of lifestyle interventions and/or novel therapeutics. The relationship between HDL and Abeta and the potential significance of such an association needs to be validated in a larger longitudinal study.

Stress infantil e desempenho escolar - avaliação de crianças de 1ª a 4ª série de uma escola pública do município de São Paulo / Stress in children and their performance at school: evaluation of children from the 1st to 4th grade of a public school in São Paulo city

O objetivo deste trabalho foi caracterizar o stress em crianças de 1ª a 4ª série, de uma escola pública do município de São Paulo e ainda comparar a presença ou ausência do stress com o respectivo desempenho escolar, das crianças. 342 crianças foram avaliadas pela Escala de Stress Infantil (ESI). O desempenho escolar das crianças foi obtido a partir da média de conceitos (A, B, C, D e E) fornecidos pelos professores, em sete disciplinas. E, para fins de tratamento estatístico, o desempenho escolar passou a se configurar nos seguintes critérios: forte (A), médio (B) e fraco (C). Os resultados não apontaram diferenças estatisticamente significativas. Porém, os dados mostraram que 30,1porcento das crianças apresentaram stress e, das crianças estressadas, 38,2porcento apresentaram desempenho fraco