Cognitive reserve, cortisol, and Alzheimer\u27s disease biomarkers: A memory clinic study

INTRODUCTION Cognitive reserve might mitigate the risk of Alzheimer\u27s dementia among memory clinic patients. No study has examined the potential modifying role of stress on this relation. METHODS We examined cross-sectional associations of the cognitive reserve index (CRI; education, occupational complexity, physical and leisure activities, and social health) with cognitive performance and AD-related biomarkers among 113 memory clinic patients. The longitudinal association between CRI and cognition over a 3-year follow-up was assessed. We examined whether associations were influenced by perceived stress and five measures of diurnal salivary cortisol. RESULTS Higher CRI scores were associated with better cognition. Adjusting for cortisol measures reduced the beneficial association of CRI on cognition. A higher CRI score was associated with better working memory in individuals with higher (favorable) cortisol AM/PM ratio, but not among individuals with low cortisol AM/PM ratio. No association was found between CRI and AD-related biomarkers. DISCUSSION Physiological stress reduces the neurocognitive benefits of cognitive reserve among memory clinic patients. HIGHLIGHTS Physiological stress may reduce the neurocognitive benefits accrued from cognitively stimulating and enriching life experiences (cognitive reserve [CR]) in memory clinic patients.Cortisol awakening response modified the relation between CR and P-tau181, a marker of Alzheimer\u27s disease (AD).Effective stress management techniques for AD and related dementia prevention are warranted

Lifestyle Factors Are Important Contributors to Subjective Memory Complaints among Patients without Objective Memory Impairment or Positive Neurochemical Biomarkers for Alzheimer’s Disease

Background/Aims: Many patients presenting to a memory disorders clinic for subjective memory complaints do not show objective evidence of decline on neuropsychological data, have nonpathological biomarkers for Alzheimer’s disease, and do not develop a neurodegenerative disorder. Lifestyle variables, including subjective sleep problems and stress, are factors known to affect cognition. Little is known about how these factors contribute to patients’ subjective sense of memory decline. Understanding how lifestyle factors are associated with the subjective sense of failing memory that causes patients to seek a formal evaluation is important both for diagnostic workup purposes and for finding appropriate interventions and treatment for these persons, who are not likely in the early stages of a neurodegenerative disease. The current study investigated specific lifestyle variables, such as sleep and stress, to characterize those patients that are unlikely to deteriorate cognitively. Methods: Two hundred nine patients (mean age 58 years) from a university hospital memory disorders clinic were included. Results: Sleep problems and having much to do distinguished those with subjective, but not objective, memory complaints and non-pathological biomarkers for Alzheimer’s disease. Conclusions: Lifestyle factors including sleep and stress are useful in characterizing subjective memory complaints from objective problems. Inclusion of these variables could potentially improve health care utilization efficiency and guide interventions

The ABCC4 gene is associated with pyometra in golden retriever dogs

Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation and bacterial infection of the uterus. On average 20% of intact female dogs are affected before 10 years of age, a proportion that varies greatly between breeds (3-66%). The clear breed predisposition suggests that genetic risk factors are involved in disease development. To identify genetic risk factors associated with the disease, we performed a genome-wide association study (GWAS) in golden retrievers, a breed with increased risk of developing pyometra (risk ratio: 3.3). We applied a mixed model approach comparing 98 cases, and 96 healthy controls and identified an associated locus on chromosome 22 (p = 1.2 x 10(-6), passing Bonferroni corrected significance). This locus contained five significantly associated SNPs positioned within introns of the ATP-binding cassette transporter 4 (ABCC4) gene. This gene encodes a transmembrane transporter that is important for prostaglandin transport. Next generation sequencing and genotyping of cases and controls subsequently identified four missense SNPs within the ABCC4 gene. One missense SNP at chr22:45,893,198 (p.Met787Val) showed complete linkage disequilibrium with the associated GWAS SNPs suggesting a potential role in disease development. Another locus on chromosome 18 overlapping the TESMIN gene, is also potentially implicated in the development of the disease

Gait and dynamic balance in adults with spina bifida

BACKGROUND: Spina bifida (SB) is a complex congenital malformation, often causing impaired gait performance depending on the level and extent of malformation. Research regarding gait and balance performance in adults with SB, has not been sufficiently described yet. RESEARCH QUESTION: What are the characteristics of spatiotemporal gait parameters and balance performance in adults with SB? Further, do persons with muscle function (MF) level 3 differ regarding gait and balance performance from those with MF level 1-2? METHODS: Cross-sectional observational study at an outpatient clinic. 41 adults with SB (18-65 years), who walked regularly. Spatiotemporal parameters of gait was assessed with the APDM system and balance performance with the Mini Balance Evaluation Systems Test (Mini-BESTest). Muscle strength in the legs was assessed with 0-5 manual muscle test, and participants were classified according to level of MF into groups MF1, MF2, and MF3. Two-sided t-test was used for parametric independent variables, and Cohen's d was used for effect sizes. The Mann-Whitney U test was used for non-parametric independent data and effect size was calculated by the z value (r = z/√n). RESULTS: Mean gait speed was 0.96 (SD 0.20) m/s and mean stride length 1.08 m (SD 0.17), individuals with MF3 showed significantly slower gaitspeed and shorter stride length (p < 0.05). Lumbar rotation was 21° (SD 11), and thoracic lateral sway 15° (IQR 15) with significantley difference (p < 0.001 and p < 0.05) for individuals in MF3. Mini-BESTest showed a mean score of 11.3 (SD 6.9), and individuals with MF3 showed significantly lower scores (p ≤ 0.001). SIGNIFICANCE: Gait and balance performance was reduced compared to normative data in almost all parameters, especially in persons with less muscle function. Increased knowledge from advanced gait analysis may help healthcare professionals to design rehabilitation programmes, in order to achieve and maintain a sustainable gait and balance performance

Life-course stress, cognition, and diurnal cortisol in memory clinic patients without dementia

Aims: To examine associations of life-course stress with cognition and diurnal cortisol patterns in older adulthood, as well as potential mediation effects of diurnal cortisol patterns and perceived stress on the association between life-course stress and cognition. Methods: 127 participants without dementia were selected from a cohort of Swedish memory clinic patients. Cross-sectional associations between scores on two chronic stress questionnaires (perceived stress, stressful life events (SLEs)), five cognitive domains (overall cognition, memory, working memory, processing speed, perceptual reasoning), and two measures of diurnal cortisol patterns (total daily output, diurnal cortisol slope), as well as potential mediation effects of diurnal cortisol patterns and perceived stress on associations between life-course stress and cognition, were assessed using linear regressions. Results: Greater lifetime exposure to SLEs was associated with worse memory, working memory, and processing speed performance, but not with diurnal cortisol patterns. A greater number of SLEs in late childhood was associated with worse working memory and processing speed, while a greater number of SLEs in non-recent adulthood were associated with better overall cognition and perceptual reasoning. Greater perceived stress was associated with a flattened diurnal cortisol slope, but not with cognition. No evidence for interplay between self-reported and physiological stress markers was found in relation to cognition, although there appeared to be a significant positive indirect association between economic/legal SLEs and the diurnal cortisol slope via perceived stress

Life-course stress, cognition, and diurnal cortisol in memory clinic patients without dementia

Aims: To examine associations of life-course stress with cognition and diurnal cortisol patterns in older adulthood, as well as potential mediation effects of diurnal cortisol patterns and perceived stress on the association between life-course stress and cognition. Methods: 127 participants without dementia were selected from a cohort of Swedish memory clinic patients. Cross-sectional associations between scores on two chronic stress questionnaires (perceived stress, stressful life events (SLEs)), five cognitive domains (overall cognition, memory, working memory, processing speed, perceptual reasoning), and two measures of diurnal cortisol patterns (total daily output, diurnal cortisol slope), as well as potential mediation effects of diurnal cortisol patterns and perceived stress on associations between life-course stress and cognition, were assessed using linear regressions. Results: Greater lifetime exposure to SLEs was associated with worse memory, working memory, and processing speed performance, but not with diurnal cortisol patterns. A greater number of SLEs in late childhood was associated with worse working memory and processing speed, while a greater number of SLEs in non-recent adulthood were associated with better overall cognition and perceptual reasoning. Greater perceived stress was associated with a flattened diurnal cortisol slope, but not with cognition. No evidence for interplay between self-reported and physiological stress markers was found in relation to cognition, although there appeared to be a significant positive indirect association between economic/legal SLEs and the diurnal cortisol slope via perceived stress. Conclusions: The associations between SLEs and cognition depend on the period during which SLEs occur, but seem independent of late-life cortisol dysregulatio

Mid-life work-related stress increases dementia risk in late-life : The CAIDE 30-year study

Background: The associations between work-related stress and various health outcomes in mid-life are well documented, yet less is known about the effects on late-life cognitive process and dementia. The current study investigated the associations between work-related stress in mid-life and the development of cognitive impairment and Alzheimer’s disease in late-life. Methods: The data was derived from the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) study; a prospective cohort study. Participants were randomly selected from four independent population-based samples that completed cardiovascular surveys. First baseline examinations occurred when participants were 50 years old on average, in 1972, 1977, 1982, or 1987. A random sample of 2,000 individ- uals was selected for re-examinations (carried out in 1998 and 2005-2008), where 1,511 subjects participated in at least one re-examination. The re- examinations included an extensive neuropsychological and cognitive assessment. Follow-up time was on average 28 (S.E.M. 1⁄4 0.17) years. Work-related stress comprised the total score of two questions adminis- tered in mid-life. The questions asked participants to rate their stress related to meeting demands at work, and constant hurry at work. Groups were categorized so that those with high or medium levels of stress were compared to those with low levels or no work-related stress. Results: High levels of work-related stress in mid-life were associated with higher risk of cognitive impairment (where participants with cognitive impair- ment and dementia were compared to the group with no cognitive impair- ment) [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.1], and Alzheimer’s disease [OR, 2.1; CI, 1.1-3.9], when assessed at the first or second follow-up. Results remained significant after adjusting for age, ed- ucation, marital status, chronic health conditions, apolipoprotein E ε 4 allele (APOE ε 4), measures of hopelessness and loneliness. Conclusions: High levels of mid-life work-related stress predict the risk of developing dementia in late-life. The evidence suggests that individuals experiencing high levels of work-related stress form an important at-risk population. Preventive interventions are needed for this population in order to post- pone or prevent the development of cognitive impairment and Alzheimer’s disease.

Midlife work-related stress increases dementia risk in later life : The CAIDE 30-year study

OBJECTIVE: To investigate the associations between midlife work-related stress and mild cognitive impairment (MCI), dementia, and Alzheimer's disease later in life, in a large representative population. METHOD: Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study participants were randomly selected from independent population-based surveys (mean age 50 years). A random sample of 2,000 individuals was invited for two reexaminations including cognitive tests (at mean age 71 and mean age 78), and 1,511 subjects participated in at least one reexamination (mean follow-up 28.5 years). Work-related stress was measured using two questions on work demands that were administered in midlife. Analyses adjusted for important confounders. RESULTS: Higher levels of midlife work-related stress were associated with higher risk of MCI (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.08-1.76), dementia (OR, 1.53; CI, 1.13-2.07), and Alzheimer's disease (OR, 1.55; CI, 1.19-2.36) at the first follow-up among the CAIDE participants. Results remained significant after adjusting for several possible confounders. Work-related stress was not associated with MCI and dementia during the extended follow-up. DISCUSSION: Midlife work-related stress increases the risk for MCI, dementia, and Alzheimer's disease in later life. The association was not seen after the extended follow-up possibly reflecting selective survival/participation, heterogeneity in dementia among the oldest old, and a critical time window for the effects of midlife stress