Cortical gyrification in relation to age and cognition in older adults

Gyrification of the cerebral cortex changes with aging and relates to development of cognitive function during early life and midlife. Little is known about how gyrification relates to age and cognitive function later in life. We investigated this in 4397 individuals (mean age: 63.5 years, range: 45.7 to 97.9) from the Rotterdam Study, a population-based cohort. Global and local gyrification were assessed from T1-weighted images. A measure for global cognition, the g-factor, was calculated from five cognitive tests. Older age was associated with lower gyrification (mean difference per year ​= ​−0.0021; 95% confidence interval ​= ​−0.0025; −0.0017). Non-linear terms did not improve the models. Age related to lower gyrification in the parietal, frontal, temporal and occipital regions, and higher gyrification in the medial prefrontal cortex. Higher levels of the g-factor were associated with higher global gyrification (mean difference per g-factor unit ​= ​0.0044; 95% confidence interval ​= ​0.0015; 0.0073). Age and the g-factor did not interact in relation to gyrification (p ​> ​0.05). The g-factor bilaterally associated with gyrification in three distinct clusters. The first cluster encompassed the superior temporal gyrus, the insular cortex and the postcentral gyrus, the second cluster the lingual gyrus and the precuneus, and the third cluster the orbitofrontal cortex. These clusters largely remained statistically significant after correction for cortical surface area. Overall, the results support the notion that gyrification varies with aging and cognition during and after midlife, and suggest that gyrification is a potential marker for age-related brain and co

Trajectories of imaging markers in brain aging: the Rotterdam Study

With aging, the brain undergoes several structural changes. These changes reflect the normal aging process and are therefore not necessarily pathologic. In fact, better understanding of these normal changes is an important cornerstone to also disentangle pathologic changes. Several studies have investigated normal brain aging, both cross-sectional and longitudinal, and focused on a broad range of magnetic resonance imaging (MRI) markers. This study aims to comprise the different aspects in brain aging, by performing

Hearing loss and cognitive decline in the general population: a prospective cohort study

Background: Previous studies identifying hearing loss as a promising modifiable risk factor for cognitive decline mostly adjusted for baseline age solely. As such a faster cognitive decline at a higher age, which is expected considering the non-linear relationship between cognition and age, may have been overlooked. Therefore it remains uncertain whether effects of hearing loss on cognitive decline extend beyond age-related declines of cognitive function. Methods: 3,590 non-demented participants were eligible for analysis at baseline, and a maximum of 837 participants were eligible for the longitudinal analysis. Hearing loss was defined at baseline. Cognitive function was measured at baseline and at follow-up (4.4 years [SD: 0.2]). Multivariable linear regression analysis was used for the cross-sectional analysis. Linear mixed models were used to assess the longitudinal association between hearing loss and cognitive decline over time while adjusting for confounders and the interaction of age and follow-up time. Results: Hearing loss was associated with lower cognitive function at baseline. Moreover, hearing loss was associated with accelerated cognitive decline over time on a memory test. After additionally adjusting for the interaction between age and follow-up time, we found that hearing loss did not accelerate cognitive decline anymore. Conclusions: Hearing loss was associated with lowe

Trajectories of Cognitive and Motor Function Between Ages 45 and 90 Years: A Population-Based Study

BACKGROUND: To establish trajectories of cognitive and motor function, and to determine the sequence of change across individual tests in community-dwelling individuals aged 45-90 years. METHOD: Between 1997 and 2016, we repeatedly assessed cognitive function with 5 tests in 9514 participants aged 45-90 years from the population-based Rotterdam Study. Between 1999 and 2016, we measured motor function with 3 tests in 8297 participants. All participants were free from dementia, stroke, and parkinsonism. We assessed overall and education-specific cognitive and motor trajectories using linear mixed models with age as time scale. Next, we determined the sequence of change across individual tests. RESULTS: The number of assessments per participant ranged between 1 and 6 (mean interval, years [SD]: 5.1 [1.4]) for cognitive function, and 1 and 4 (5.4 [1.4]) for motor function. Cognitive and motor trajectories declined linearly between ages 45 and 65 years, followed by steeper declines after ages 65-70 years. Lower educated participants had lower cognitive function at age 45 years (baseline), and declined faster on most cognitive, but not on motor tests than higher educated participants. Up to a 25-year age difference between the fastest and slowest declining test scores was observed. CONCLUSIONS: On a population-level, cognitive and motor function decline similarly. Compared to higher educated individuals, lower educated individuals had lower cognitive f

Season of birth and the risk of dementia in the population‐based Rotterdam Study

Early-life environmental factors have been suggested in the pathophysiology of dementia. Season of birth has previously been used as a proxy for these external exposures. We investigated the link between season of birth and the risk of dementia and further explored underlying pathways by studying structural brain changes on MRI. From the Dutch, population-based Rotterdam Study, 12,964 participants born between 1887 and 1960 were followed between 1990 and 2018 for dementia. Cox regression was conducted to assess the association between season of birth and dementia. In addition, we distinguished between mild and cold winters. The association of season of birth with structural brain markers on MRI was examined in 5237 participants. The risk of dementia in participants born in winter and fall was higher than of those born in summer (hazard ratio (HR) 1.15 [95% confidence interval (CI) 1.01–1.31] for winter and HR 1.17 [95% CI 1.01–1.33] for fall), especially for Alzheimer’s disease (HR 1.23 [1.06–1.43] for winter and HR 1.15 [95% CI 0.99–1.35] for fall). The risk was particularly increased for participants born in a cold winter. Except for slightly lower hippocampus in fall born participants (β − 0.03; 95% CI − 0.06 to 0.00), we did not find associations with brain imaging markers. In conclusion, winter and fall births were associated with a higher incidence of dementia, especially of AD. We did not find evidence for structural brain changes as an underlying mechanism

REPEATABILITY OF BOLUS KINETICS ULTRASOUND PERFUSION IMAGING FOR THE QUANTIFICATION OF CEREBRAL BLOOD FLOW

Ultrasound perfusion imaging (UPI) can be used for the quantification of cerebral perfusion. In a neuro-intensive care setting, repeated measurements are required to evaluate changes in cerebral perfusion and monitor therapy. The aim of this study was to determine the repeatability of UPI in quantification of cerebral perfusion. UPI measurement of cerebral perfusion was performed three times in healthy patients. The coefficients of variation of the three bolus injections were calculated for both time- and volume-derived perfusion parameters in the macro- and microcirculation. The UPI time-dependent parameters had overall the lowest CVs in both the macro- and microcirculation. The volume-related parameters had poorer repeatability, especially in the microcirculation. Both intra-observer variability and inter-observer variability were low. Although UPI is a promising tool for the bedside measurement of cerebral perfusion, improvement of the technique is required before implementation in routine clinical practice

Aging-dependent genetic effects associated to ADHD predict longitudinal changes of ventricular volumes in adulthood

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood-onset disorder that can persist into adult life. Most genetic studies have focused on investigating biological mechanisms of ADHD during childhood. However, little is known about whether genetic variants associated with ADHD influence structural brain changes throughout adulthood. Methods: Participant of the study were drawn from a population-based sample of 3,220 healthy individuals drawn from the Rotterdam Study, with at least two magnetic resonance imaging (MRI)-scans (8,468 scans) obtained every 3-4 years. We investigate associations of genetic single nucleotide polymorphisms (SNPs) that have previously been identified in genome-wide association studies for ADHD, and trajectories of global and subcortical brain structures in an adult population (aged 50 years and older), acquired through MRI. We also evaluated the existence of age-dependent effects of these genetic variants on trajectories of brain structures. These analyses were reproduced among individuals 70 years of age or older to further explore aging-dependent mechanisms. We additionally tested baseline associations using the first MRI-scan of the 3,220 individuals. Results: We observed significant age-dependent effects on the rs212178 in trajectories of ventricular size (lateral ventricles, P= 4E-05; inferior lateral ventricles, P=3.8E-03; third ventricle, P=2.5E-03; fourth ventricle, P=5.5E-03). Specifically, carriers of the G allele, which was reported as protective for ADHD, had a smaller increase of ventricular size compared with homozygotes for the A allele in elder stages. Post hoc analysis on the subset of individuals older than 70 years of age reinforced these results (lateral ventricles, P=7.3E-05). In addition, the rs4916723, and the rs281324 displayed nominal significant age-dependent effects in trajectories of the amygdala volume (P=1.4E-03), and caudate volume (P=1.8E-03), respectively. Conclusions: To the best of our knowledge, this is the first study suggesting the involvement of protective genetic variants for ADHD on prevention of brain atrophy during adulthood.The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. This research is supported by the Dutch Technology Foundation STW (12723), which is part of the NWO, and which is partly funded by the Ministry of Economic Affairs. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (project: ORACLE, grant agreement No: 678543)

Potential of Contrast-Enhanced Ultrasound as a Bedside Monitoring Technique in Cerebral Perfusion: a Systematic Review

Contrast-enhanced ultrasound (CEUS) has been suggested as a new method to measure cerebral perfusion in patients with acute brain injury. In this systematic review, the tolerability, repeatability, reproducibility and accuracy of different CEUS techniques for the quantification of cerebral perfusion were assessed. We selected studies published between January 1994 and March 2017 using CEUS to measure cerebral perfusion. We included 43 studies (bolus kinetics n = 31, refill kinetics n = 6, depletion kinetics n = 6) with a total of 861 patients. Tolerability was reported in 28 studies describing 12 patients with mild and transient side effects. Repeatability was assessed in 3 studies, reproducibility in 2 studies and accuracy in 19 studies. Repeatability was high for experienced sonographers and significantly lower for less experienced sonographers. Reproducibility of CEUS was not clear. The sensitivity and specificity of CEUS for the detection of cerebral ischemia ranged from 75% to 96% and from 60% to 100%. Limited data on repeatability, reproducibility and accuracy may suggest that this technique could be feasible for use in acute brain injury patients