Abstract 36: Association of Parental Stroke with Cognitive and Brain MRI Measures in Offspring - The Framingham Heart Study

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
GALIT WEINSTEIN ◽  
Alexa Beiser ◽  
Rhoda Au ◽  
Charles DeCarli ◽  
Philip A Wolf ◽  
...  

Objectives- Parental stroke is related to an increased risk of stroke among the offspring. Vascular related brain changes, however, often occur before clinical stroke and the association of parental history of stroke and structural brain measures and cognition has not been fully explored. We hypothesized that prospectively verified parental stroke will be associated with increased vascular brain injury and poorer cognitive performance. Methods- A total of 1,297 Framingham offspring (mean age: 61 ± 9 years, 54% women) were studied. Of these, 9.9% had prospectively identified stroke in one or both parents before age 65. Volumetric brain MRI measures of total cerebral brain volume (TCBV), regional brain volumes, white matter hyperintensity volume (WMHV), and covert brain infarcts (CBI) and performance on tests of verbal memory, abstract reasoning, verbal learning and visuospatial memory (VRd) were compared for offspring with and without parental history of stroke. All measures were assessed cross-sectionally and longitudinally (mean duration of follow-up was 6.1±1.2 years). We used models adjusted only for age, sex, education and also additionally adjusted for vascular risk factors and for WMHV as an index of subclinical vascular brain injury. GEE models were used to adjust for sibling relationships among offspring. Results- Higher WMHV (β±SE=0.17±0.08;p=0.027) and lower VRd scores (β±SE=-0.80±0.34; p=0.017) at baseline were found in offspring with parental history of stroke. In addition, participants with parental stroke by age 65 years were more likely to be in the highest quintile of increase in WMHV (OR=1.87;p=0.04) as well as worsening executive function (Trails B-A) (OR:1.81;p=0.03). Parental stroke was not associated with total and regional brain volumes or with memory, abstract reasoning and verbal learning. Conclusions- In our community-based sample of middle-aged asymptomatic subjects, the occurrence of parental stroke by age 65 years is associated with higher baseline WMHV and with a more rapid increase in WMHV. Further, parental stroke is also associated with poorer performance on VRd and a decline in executive function. The effects on baseline WMH and VRd were substantial equivalent to 2.8 and 7 years of brain aging, respectively.

2020 ◽  
Vol 35 (5) ◽  
pp. 1211-1221 ◽  
Author(s):  
Hui Wang ◽  
Fei Li ◽  
Maohua Miao ◽  
Yongfu Yu ◽  
Honglei Ji ◽  
...  

Abstract STUDY QUESTION Is a maternal history of spontaneous abortion (SA) associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring? SUMMARY ANSWER Our results suggest an association between maternal history of SA and ADHD in offspring, with the risk increasing with the number of maternal SA and highest in the firstborn children whose mothers had had recurrent SAs after adjusting for a number of potential confounders. WHAT IS KNOWN ALREADY A history of SA has been associated with more complications in next pregnancies and adverse childbirth outcomes, which are risk factors for ADHD in the offspring. However, no previous study has investigated whether maternal SA increases risk of ADHD in the offspring. STUDY DESIGN, SIZE, DURATION This population-based study included all live-born children in Denmark from 1 January 1995 to 31 December 2012 (n = 1 062 667). All children were followed from 3 years of age until the day of ADHD diagnosis, death, emigration or 31 December 2016, whichever came first. PARTICIPANTS/MATERIALS, SETTING, METHODS There were 130 206 (12.2%) children born to mothers who had at least one SA. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE During a median follow-up of 9.4 years (interquartile range, 5.4–14.3), 25 747 children were diagnosed with ADHD. Overall, children of mothers with a history of SA had an increased rate of ADHD (HR, 1.11; 95% CI, 1.07 to 1.15). The HRs increased with the number of maternal SA, 1.09 (95% CI, 1.05 to 1.13) for one SA and 1.22 (95% CI, 1.12 to 1.33) for at least two SAs, respectively. These findings were consistent when we took into consideration a number of factors, such as maternal socioeconomic status, type of SA, birth order, parental history of psychiatric disorders, pregnancy characteristics and adverse birth outcomes. LIMITATIONS, REASONS FOR CAUTION Misclassification of SA was possible as we used population-based register data to capture maternal history of SA. However, any misclassification of maternal history of SA would be non-differential with regard to the diagnosis of ADHD in offspring, which generally leads to underestimation of the associations. Furthermore, probabilistic sensitivity analysis suggested that only 1% of change in the estimate may have been due to misclassification of SA. WIDER IMPLICATIONS OF THE FINDINGS SA is quite frequent (varying from 15 to 20%), and a small increase of neurodevelopmental problems in offspring could have major public health implications. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from the National Natural Science Foundation of China (No. 81703237, No. 81530086 and No. 81761128035), National Key Research and Development Program (2018YFC1002801, 2016YFC1000505), Shanghai Municipal Commission of Health and Family Planning (No. 2017ZZ02026, No. 2017EKHWYX-02), the Novo Nordisk Foundation (NNF18OC0052029), the Danish Council for Independent Research (DFF-6110-00019), the Nordic Cancer Union (176673, 186200 and R217-A13234-18-S65), Karen Elise Jensens Fond (2016) and Xinhua Hospital of Shanghai Jiao Tong University School of Medicine (2018YJRC03). All authors report no conflict of interest. TRIAL REGISTRATION NUMBER NA.


Author(s):  
Claire E Kelly ◽  
Deanne K Thompson ◽  
Alicia J Spittle ◽  
Jian Chen ◽  
Marc L Seal ◽  
...  

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA cohort of MLPT infants had brain MRI at approximately TEA (38–44 weeks’ postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years’ corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics.Results189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes.ConclusionsRegional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children.


Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Matthew Mesley ◽  
Ross Puffer ◽  
Charles Laymon ◽  
Brian Lopresti ◽  
Kathryn Edelman ◽  
...  

Abstract INTRODUCTION TBI (traumatic brain injury) is associated with an increased risk of late neurodegeneration in chronic TBI survivors. The underlying pathophysiology of trauma-related neurodegeneration is hypothesized to involve a tauopathy, with p-tau deposited in beta-pleated sheets. Current research focuses on identifying strategies to detect trauma-related neurodegeneration in-Vivo. [F-18]AV-1451, a tau-specific PET radiotracer, may detect hyper-phosphorylated tau deposits in living patients. METHODS Participants with a history of TBI >6 mo prior with concern for cognitive decline with age-matched controls were recruited. Subjects were classified into three groups: few (=3 TBI exposures), intermediate (4–10 exposures), and numerous (>10 exposures). Participants underwent PET imaging with [F-18]AV-1451, and qualitative and semi-quantitative (SUVR) analyses of radiotracer retention were performed. Visual classification of tau positivity (+/−) was performed with absence of established positivity thresholds for [F-18]AV-1451 SUVR values. All subjects underwent neuropsychological evaluation, including measures of processing speed, executive function, and memory. RESULTS Twenty-seven TBI subjects and 7 controls were enrolled. A total of 9 participants were categorized as few, 2 as intermediate, 7 as numerous. All TBI subjects demonstrated impairment on at least one neurocognitive measure, while control subjects had normal neuropsychological test results. Analysis of [F-18]AV-1451 uptake patterns demonstrated evidence of tauopathy in 3 subjects, based on visual reads. Significantly increased [F-18]AV-1451 retention was noted in occipital gray matter, posterior cingulate gyrus, and parietal cortex in these 3 tau (+) TBI subjects compared to 24 TBI subjects visually classified as tau (−) and also normal controls. CONCLUSION Evidence of tauopathy, indicative of trauma-related neurodegeneration, was noted in 3 chronic TBI subjects, all of whom were categorized as numerous (>10) TBI exposures and cognitive deficits on neuropsychological testing. No tau PET [F-18]AV-1451 uptake was noted in control participants or in participants categorized as few or intermediate. The data represent a possible [F-18]AV-1451 PET uptake pattern associated with a clinical neurodegeneration syndrome in repetitive TBI.


Neurology ◽  
2017 ◽  
Vol 88 (17) ◽  
pp. 1642-1649 ◽  
Author(s):  
Frank J. Wolters ◽  
Sven J. van der Lee ◽  
Peter J. Koudstaal ◽  
Cornelia M. van Duijn ◽  
Albert Hofman ◽  
...  

Objective:To determine the association of parental family history with risk of dementia by age at onset and sex of affected parent in a population-based cohort.Methods:From 2000 to 2002, we assessed parental history of dementia in participants without dementia of the Rotterdam Study. We investigated associations of parental history with risk of dementia until 2015, adjusting for demographics, cardiovascular risk factors, and known genetic risk variants. Furthermore, we determined the association between parental history and markers of neurodegeneration and vascular disease on MRI.Results:Of 2,087 participants (mean age 64 years, 55% female), 407 (19.6%) reported a history of dementia in either parent (mean age at diagnosis 79 years). During a mean follow-up of 12.2 years, 142 participants developed dementia. Parental history was associated with risk of dementia independently of known genetic risk factors (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12–2.48), in particular when parents were diagnosed at younger age (<80 years: HR 2.58, 95% CI 1.61–4.15; ≥80 years: HR 1.01, 95% CI 0.58–1.77). Accordingly, age at diagnosis in probands was highly correlated with age at diagnosis in their parents <80 years (r = 0.57, p = 0.001) but not thereafter (r = 0.17, p = 0.55). Among 1,161 participants without dementia with brain MRI, parental history was related to lower cerebral perfusion and higher burden of white matter lesions and microbleeds. Dementia risk and MRI markers were similar for paternal and maternal history.Conclusions:Parental history of dementia increases risk of dementia, primarily when age at parental diagnosis is <80 years. Unexplained heredity may be attributed in part to cerebral hypoperfusion and small vessel disease. We found no evidence of preferential maternal compared to paternal transmission.


2019 ◽  
Vol 44 (4) ◽  
pp. 781-789
Author(s):  
Andraea Van Hulst ◽  
Marina Ybarra ◽  
Marie-Eve Mathieu ◽  
Andrea Benedetti ◽  
Gilles Paradis ◽  
...  

Abstract Objective To identify determinants for the development of “normal weight metabolically unhealthy” (NWMU) profiles among previously metabolically healthy normal weight children. Methods The QUALITY cohort comprises youth 8–10 years of age with a parental history of obesity (n = 630). Of these, normal weight children with no metabolic risk factors were identified and followed up 2 years later (n = 193). Children were classified as NWMU if they remained normal weight but developed at least one cardiometabolic risk factor. They were classified as normal weight metabolically healthy otherwise. Multivariable logistic regression models were used to identify whether adiposity (anthropometrics and DXA), lifestyle habits (physical activity, screen time, vegetables, and fruit- and sugar-sweetened beverages intake), fitness, and family history of cardiometabolic disease were associated with new onset NWMU. Results Of the 193 normal weight and metabolically healthy children at baseline, 45 (23%) became NWMU 2 years later (i.e., 48% had elevated HDL cholesterol, 13% had elevated triglycerides, and 4% had impaired fasting glucose). Changes in adiposity between baseline and follow-up were associated with an increased risk of NWMU for all adiposity measures examined (e.g., for ∆zBMI OR = 3.95; 95% CI: 1.76, 8.83). Similarly, a 2-year change in screen time was associated with incident NWMU status (OR = 1.24; 95% CI 1.04, 1.49). Conclusions Children who increase their adiposity levels as they enter puberty, despite remaining normal weight, are at risk of developing cardiometabolic risk factors. Studies examining long-term consequences of NWMU profiles in pediatrics are needed to determine whether changes in screening practice are warranted.


2021 ◽  
pp. 1-10
Author(s):  
Emer R. McGrath ◽  
Jayandra J. Himali ◽  
Daniel Levy ◽  
Qiong Yang ◽  
Charles S. DeCarli ◽  
...  

Background: Epidermal growth factor containing fibulin extracellular matrix protein-1 (EFEMP1) has been associated with increased white matter hyperintensities (WMH) burden and disorders of premature aging and may have a shared pathophysiological role in the development of WMH and dementia. Objective: To determine the association between plasma EFEMP1 levels and MRI markers of vascular brain injury and incident all-cause and Alzheimer’s disease (AD) dementia. Methods: We measured plasma EFEMP1 levels in 1597 [53% women, mean age 68.7 (SD 5.7) years] dementia-free Framingham Offspring cohort participants between 1998–2001 and subsequently followed them for incident dementia. Secondary outcomes included stroke, structural MRI brain measures and neurocognitive test performance. Results: During a median 11.8 [Q1, Q3 : 7.1, 13.3] year follow-up, 131 participants developed dementia. The highest quintile of plasma EFEMP1, compared to the bottom four quintiles, was associated with an increased risk of time to incident all-cause dementia (HR 1.77, 95% CI 1.18–2.64) and AD dementia (HR 1.76, 95% CI 1.11–2.81) but not with markers of vascular brain injury (WMH, covert brain infarcts or stroke). Higher circulating EFEMP1 concentrations were also cross-sectionally associated with lower total brain (β±SE, –0.28±0.11, p = 0.01) and hippocampal volumes (–0.006±0.003, p = 0.04) and impaired abstract reasoning (Similarities test, –0.18±0.08, p = 0.018 per standard deviation increment in EFEMP1). Conclusion: Elevated circulating EFEMP1 is associated with an increased risk of all-cause and AD dementia, smaller hippocampal and total brain volumes, and poorer cognitive performance. EFEMP1 may play an important biological role in the development of AD dementia. Further studies to validate these findings are warranted.


2017 ◽  
Vol 62 (10) ◽  
pp. 3135-3150 ◽  
Author(s):  
Rachel Woolhouse ◽  
Audrey McKinlay ◽  
Randolph C. Grace

Relatively little is known about the characteristics of female offenders. Here, we studied the prevalence of traumatic brain injury (TBI) and mental health issues in an exclusively female prison population in New Zealand. Participants ( N = 38) were recruited from all security levels at Christchurch Women’s Prison. Measures for depression, anxiety, and stress, sleep, and a history of TBI were administered; 94.7% (36/38) of participants presented with a history of TBI. Younger age at first injury was associated with an increased risk of mental health problems. The study concludes that TBI is highly prevalent among female offenders and may be linked to increased mental health problems. TBI should be considered as an important factor in offender pathways and treatment programs.


2018 ◽  
Vol 24 (10) ◽  
pp. 1084-1098 ◽  
Author(s):  
Tess E.K. Cersonsky ◽  
Sarah Morgan ◽  
Sarah Kellner ◽  
Daphne Robakis ◽  
Xinhua Liu ◽  
...  

AbstractObjectives:Essential tremor (ET) confers an increased risk for developing both amnestic and non-amnestic mild cognitive impairment (MCI). Yet, the optimal measures for detecting mild cognitive changes in individuals with this movement disorder have not been established. We sought to identify the cognitive domains and specific motor-free neuropsychological tests that are most sensitive to mild deficits in cognition as defined by a Clinical Dementia Rating (CDR) of 0.5, which is generally associated with a clinical diagnosis of MCI.Methods:A total of 196 ET subjects enrolled in a prospective, longitudinal, clinical-pathological study underwent an extensive motor-free neuropsychological test battery and were assigned a CDR score. Logistic regression analyses were performed to identify the neuropsychological tests which best identified individuals with CDR of 0.5 (mild deficits in cognition)versus0 (normal cognition).Results:In regression models, we identified five tests in the domains of Memory and Executive Function which best discriminated subjects with CDR of 0.5versus0 (86.9% model classification accuracy). These tests were the California Verbal Learning Test II Total Recall, Logical Memory II, Verbal-Paired Associates I, Category Switching Fluency, and Color-Word Inhibition.Conclusions:Mild cognitive difficulty among ET subjects is best predicted by combined performance on five measures of memory and executive function. These results inform the nature of cognitive dysfunction in ET and the creation of a brief cognitive battery to assess patients with ET for cognitively driven dysfunction in life that could indicate the presence of MCI. (JINS, 2018,24, 1084–1098)


2019 ◽  
Vol 21 (1) ◽  
pp. 32-46 ◽  
Author(s):  
Ileana Ratiu ◽  
Tamiko Azuma

AbstractBackground and objective:Adults with a history of traumatic brain injury (TBI) often show deficits in executive function (EF), including the ability to inhibit, switch, and attend to task relevant information. Although performances differences between bilinguals and monolinguals have been observed in EF tasks, there is little research on the effect of TBI on EF in bilinguals. In this study, an ecologically valid standardized measure and experimental computerized tasks of EF were administered to Spanish-English bilingual adults with and without history of mild traumatic brain injury (mTBI).Method:Twenty-two bilinguals with a history of mTBI [mean age=20.1 years, SD=3.7; education=13.4 years, SD=0.7] and 20 control bilinguals [mean age=20.8 years, SD=3.6; education=13.7 years, SD=1.1], matched for age and education, completed language proficiency questionnaires, the Functional Assessment of Verbal Reasoning and Executive Strategies (FAVRES), English and Spanish language assessments, and a Flanker task (a test of inhibition).Results:Performance was analyzed using analyses of covariance. The results revealed that bilinguals with a history of mTBI performed worse on both the standardized assessment (FAVRES) and inhibition task. Interestingly, self-reported EF deficits were consistent with performance on these measures.Conclusion:The findings of this study provide useful information regarding assessment of EF deficits in bilinguals with a history mTBI. Computerized experimental tasks of EF may also prove useful in the assessment of EF in individuals with mTBI.


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