Cross-sectional associations between short and mid-term blood pressure variability, cognition, and vascular stiffness in older adults.

Background: High blood pressure variability (BPV), particularly in older age, appears to be an independent risk factor for incident dementia. The current study aimed to investigate the association between different BPV measures (short- and mid-term BPV including circadian patterns) and cognitive functioning as well as vascular stiffness measures to better understand the role that BPV plays in cognitive impairment. Methods: 70 older adults (60-80-year-olds) without dementia completed a cognitive test battery and had their blood pressure (BP) assessed via a 24-hour ambulatory BP monitor (divided into sleep and wake for short-term BPV) and 4-day morning and evening home-based BP monitor (for day-to-day BPV). Arterial stiffness was evaluated via pulse wave analysis and pulse wave velocity (PWV) and cerebrovascular pulsatility was assessed via transcranial doppler sonography of the middle cerebral arteries. Results: High systolic as well as diastolic short- and mid-term BPV were associated with poorer cognitive functioning, independent of the mean BP. Higher short-term BPV was associated with poorer attention and psychomotor speed, whilst day-to-day BPV was negatively linked with executive functioning. Circadian BP patterns (dipping and morning BP surge) showed no significant relationships with cognition after adjusting for covariates. Higher systolic short-term BPV was associated with higher arterial stiffness (PWV) and higher diastolic day-to-day BPV was linked with lower arterial stiffness. No significant associations between BPV measures and cerebrovascular pulsatility were present. Conclusion: High BPV, independently of the mean BP, is associated with lower cognitive performance and increased arterial stiffness in older adults without clinically-relevant cognitive impairment. This highlights the role of systolic and diastolic BPV as a potential early clinical marker for cognitive impairment.

The relationship between long-term blood pressure variability and cortical thickness in older adults.

High blood pressure variability (BPV) is a risk factor for cognitive decline and dementia, but its association with cortical thickness is not well understood. Here we use a topographical approach, to assess links between long-term BPV and cortical thickness in 478 (54% men at baseline) community dwelling older adults (70-88 years) from the ASPirin in Reducing Events in the Elderly NEURO sub-study. BPV was measured as average real variability, based on annual visits across three years. Higher diastolic BPV was significantly associated with reduced cortical thickness in multiple areas, including temporal (banks of the superior temporal sulcus), parietal (supramarginal gyrus, post-central gyrus), and posterior frontal areas (pre-central gyrus, caudal middle frontal gyrus), while controlling for mean BP. Higher diastolic BPV was associated with faster progression of cortical thinning across the three years. Diastolic BPV is an important predictor of cortical thickness, and trajectory of cortical thickness, independent of mean blood pressure. This finding suggests an important biological link in the relationship between BPV and cognitive decline in older age.

Monotonous driving induces shifts in spatial attention as a function of handedness.

Current evidence suggests that the ability to detect and react to information under lowered alertness conditions might be more impaired on the left than the right side of space. This evidence derives mainly from right-handers being assessed in computer and paper-and-pencil spatial attention tasks. However, there are suggestions that left-handers might show impairments on the opposite (right) side compared to right-handers with lowered alertness, and it is unclear whether the impairments observed in the computer tasks have any real-world implications for activities such as driving. The current study investigated the alertness and spatial attention relationship under simulated monotonous driving in left- and right-handers. Twenty left-handed and 22 right-handed participants (15 males, mean age = 23.6 years, SD = 5.0 years) were assessed on a simulated driving task (lasting approximately 60 min) to induce a time-on-task effect. The driving task involved responding to stimuli appearing at six different horizontal locations on the screen, whilst driving in a 50 km/h zone. Decreases in alertness and driving performance were evident with time-on-task in both handedness groups. We found handedness impacts reacting to lateral stimuli differently with time-on-task: right-handers reacted slower to the leftmost stimuli, while left-handers showed the opposite pattern (although not statistically significant) in the second compared to first half of the drive. Our findings support suggestions that handedness modulates the spatial attention and alertness interactions. The interactions were observed in a simulated driving task which calls for further research to understand the safety implications of these interactions for activities such as driving.

Long-Chain Omega-3 Fatty Acid Intake Is Associated with Age but not Cognitive Performance in an Older Australian Sample.

BACKGROUND: Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) are essential nutrients and may be capable of delaying age-related cognitive decline. However, previous studies indicate that Australians are not meeting recommendations for LCn-3 PUFA intake. The current study therefore examined LCn-3 PUFA intake in an older Australia sample, as well as associations between LCn-3 PUFA intake and cognitive function. METHODS: Cross-sectional data were collected from 90 adults aged 50 to 80 years. LCn-3 PUFA intake was assessed using a food frequency questionnaire and red blood cell fatty acid profiles were used to calculate the Omega-3 Index (RBC n-3 index). Cognitive function was measured using Addenbrooke's Cognitive Examination-III. RESULTS: Positive associations were observed between age and RBC n-3 index (b=0.06, 95% CI: 0.01 - 0.10, P=0.01), and age and LCn-3 PUFA intake from fish oil capsules (b=17.5, 95% CI: 2.4 - 32.5 mg/day, P=0.02). When adjusting for LCn-3 PUFA from fish oil capsules, the association between age and RBC n-3 index was no longer significant. No associations were observed between LCn-3 PUFA intake and cognitive function. CONCLUSION: LCn-3 PUFA and fish oil consumption increased with age in this sample of older Australians, particularly due to supplement intake. However, LCn-3 PUFA intake was not associated with cognitive function.

The relationship between alertness and spatial attention under simulated shiftwork.

Higher and lower levels of alertness typically lead to a leftward and rightward bias in attention, respectively. This relationship between alertness and spatial attention potentially has major implications for health and safety. The current study examined alertness and spatial attention under simulated shiftworking conditions. Nineteen healthy right-handed participants (M = 24.6 ± 5.3 years, 11 males) completed a seven-day laboratory based simulated shiftwork study. Measures of alertness (Stanford Sleepiness Scale and Psychomotor Vigilance Task) and spatial attention (Landmark Task and Detection Task) were assessed across the protocol. Detection Task performance revealed slower reaction times and higher omissions of peripheral (compared to central) stimuli, with lowered alertness; suggesting narrowed visuospatial attention and a slight left-sided neglect. There were no associations between alertness and spatial bias on the Landmark Task. Our findings provide tentative evidence for a slight neglect of the left side and a narrowing of attention with lowered alertness. The possibility that one's ability to sufficiently react to information in the periphery and the left-side may be compromised under conditions of lowered alertness highlights the need for future research to better understand the relationship between spatial attention and alertness under shiftworking conditions.

Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. METHODS: We systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. RESULTS: A total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. CONCLUSIONS: Different methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.

Variability in lateralised blood flow response to language is associated with language development in children aged 1-5 years.

The developmental trajectory of language lateralisation over the preschool years is unclear. We explored the relationship between lateralisation of cerebral blood flow velocity response to object naming and cognitive performance in children aged 1-5 years. Functional transcranial Doppler ultrasound was used to record blood flow velocity bilaterally from middle cerebral arteries during a naming task in 58 children (59% male). At group level, the Lateralisation Index (LI) revealed a greater relative increase in cerebral blood flow velocity within the left as compared to right middle cerebral artery. After controlling for maternal IQ, left-lateralised children displayed lower expressive language scores compared to right- and bi-lateralised children, and reduced variability in LI. Supporting this, greater variability in lateralised response, rather than mean response, was indicative of greater expressive language ability. Findings suggest that a delayed establishment of language specialisation is associated with better language ability in the preschool years.

APOE and ACE polymorphisms and dementia risk in the older population over prolonged follow-up: 10 years of incidence in the MRC CFA Study.

BACKGROUND: dementia risk conferred by apolipoprotein-E (APOE) and angiotensin-1-converting enzyme (ACE) polymorphisms have been reported for the MRC Cognitive Function and Ageing Study (CFAS) at 6-year follow-up. We concentrate on incident dementia risk over 10 years. METHODS: participants come from MRC CFAS, a multi-centre longitudinal population-based study of ageing in England and Wales. Three follow-up waves of data collection were used: 2, 6 and 10 years. Logistic regressions were undertaken to investigate associations between APOE (n = 955) and ACE (n = 856) alleles/genotypes and incident dementia. Two types of control groups were used: non-demented and highly functioning non-demented. Results were back-weighted. RESULTS: compared to APOE epsilon3, epsilon2 conferred protection of odds ratio (OR) = 0.3 (95% confidence interval, CI = 0.1-0.6) and epsilon4 risk of OR = 2.9 (95% CI = 1.7-4.9) for incident dementia. Compared to epsilon3/epsilon3, the epsilon3/epsilon4 and epsilon4/epsilon4 genotypes conferred risks of OR = 3.6 (95% CI = 1.8-7.3) and OR = 7.9 (95% CI = 1.6-39.2), respectively. The epsilon3/epsilon2 genotype protected against dementia (OR = 0.2, 95% CI = 0.1-0.7), and epsilon2/epsilon2 had a similar protective effect but with wide CIs (OR = 0.3, 95% CI = 0.1-1.7). Restricting the control group accentuated these differentials. The effects of ACE alleles/genotypes on incident dementia risk were small. CONCLUSIONS: APOE but not ACE is associated with late-onset incident dementia in the population. Using longer term follow-up with proper adjustment for attrition and incident cases increases estimates of risk.