The Developing Brain in Down Syndrome

Author(s):  
Nancy Raitano Lee ◽  
Manisha D. Udhnani ◽  
Taralee Hamner

Research on the developing brain in persons with Down syndrome has grown in recent years thanks to advances in neuroimaging approaches that are safe for pediatric populations. This literature documents global reductions in total brain volume as well as specific alterations in both cortical and subcortical structures. These include reductions in hippocampal and cerebellar volumes (that are in excess of reduced total brain volume) as well as abnormalities in frontal and temporal lobe anatomy. Recent neuroimaging research has highlighted the importance of using fine-grained approaches to characterizing cortical and subcortical anatomy in persons with Down syndrome as well as interpreting these findings within the context of research on typical brain development. In the current review, we attempt to synthesize this literature from a developmental perspective. Our hope is that this developmental focus will lead to discoveries about the biological underpinnings and unfolding of the learning difficulties associated with Down syndrome.

2022 ◽  
Vol 15 ◽  
Author(s):  
Eilidh MacNicol ◽  
Paul Wright ◽  
Eugene Kim ◽  
Irene Brusini ◽  
Oscar Esteban ◽  
...  

Age-specific resources in human MRI mitigate processing biases that arise from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue's relative contribution to total brain volume would change with age in the adult rat. Data from a longitudinal study of rats at 3, 5, 11, and 17 months old were used to test this hypothesis. Tissue volume was estimated from high resolution structural images using a priori information from tissue probability maps. However, existing tissue probability maps generated inaccurate gray matter probabilities in subcortical structures, particularly the thalamus. To address this issue, gray matter, white matter, and CSF tissue probability maps were generated by combining anatomical and signal intensity information. The effects of age on volumetric estimations were then assessed with mixed-effects models. Results showed that herein estimation of gray matter volumes better matched histological evidence, as compared to existing resources. All tissue volumes increased with age, and the tissue proportions relative to total brain volume varied across adulthood. Consequently, a set of rat brain templates and tissue probability maps from across the adult lifespan is released to expand the preclinical MRI community's fundamental resources.


2020 ◽  
pp. 1-10 ◽  
Author(s):  
Michael A. Mooney ◽  
Priya Bhatt ◽  
Robert J. M. Hermosillo ◽  
Peter Ryabinin ◽  
Molly Nikolas ◽  
...  

Abstract Background Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children. Methods Children 7–15 years old were recruited for a case–control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577). Results ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = −0.147 (−0.27 to −0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score. Conclusion Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.


2015 ◽  
Vol 38 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Yiran Chen ◽  
Hosung Kim ◽  
Robert Bok ◽  
Subramaniam Sukumar ◽  
Xin Mu ◽  
...  

Hyperpolarized 13C magnetic resonance imaging has recently been used to dynamically image metabolism in vivo. This technique provides the capability to investigate metabolic changes in mouse brain development over multiple time points. In this study, we used 13C magnetic resonance spectroscopic imaging and hyperpolarized 13C-1-labeled pyruvate to analyze its conversion into lactate. We also applied T2-weighted anatomical imaging to examine brain volume changes starting from postnatal day 18 (P18). We combined these results with body weight measurements for a comprehensive interpretation of mouse brain maturation. Both the produced lactate level and pyruvate to lactate conversion rate decreased with increasing age in a linear manner. Total brain volume remained the same after P18, even though body weight continued to grow exponentially. Our results have shown that the rate of metabolism of 13C-1 pyruvate to lactate in brain is high in the young mouse and decreases with age. The brain at P18 is still relatively immature and continues to develop even as the total brain volume remains the same.


2014 ◽  
Vol 45 (7) ◽  
pp. 1389-1399 ◽  
Author(s):  
H. C. Saavedra Pérez ◽  
M. A. Ikram ◽  
N. Direk ◽  
H. G. Prigerson ◽  
R. Freak-Poli ◽  
...  

BackgroundSeveral psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study.MethodThe present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter–Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test – immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms.ResultsCompared with no-grief participants, participants with complicated grief had lower scores for the Letter–Digit Substitution Test [Z-score −0.16 v. 0.04, 95% confidence interval (CI) −0.36 to −0.04, p = 0.01] and Word Fluency Task (Z-score −0.15 v. 0.03, 95% CI −0.35 to −0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI −37.6 to −0.10, p = 0.04).ConclusionsParticipants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.


Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 783-788 ◽  
Author(s):  
Jeremy P. Berman ◽  
Faye L. Norby ◽  
Thomas Mosley ◽  
Elsayed Z. Soliman ◽  
Rebecca F. Gottesman ◽  
...  

Background and Purpose— Atrial fibrillation (AF) is associated with dementia independent of clinical stroke. The mechanisms underlying this association remain unclear. In a community-based cohort, the ARIC study (Atherosclerosis Risk in Communities), we evaluated (1) the longitudinal association of incident AF and (2) the cross-sectional association of prevalent AF with brain magnetic resonance imaging (MRI) abnormalities. Methods— The longitudinal analysis included 963 participants (mean age, 73±4.4 years; 62% women; 51% black) without prevalent stroke or AF who underwent a brain MRI in 1993 to 1995 and a second MRI in 2004 to 2006 (mean, 10.6±0.8 years). Outcomes included subclinical cerebral infarctions, sulcal size, ventricular size, and, for the cross-sectional analysis, white matter hyperintensity volume and total brain volume. Results— In the longitudinal analysis, 29 (3.0%) participants developed AF after the first brain MRI. Those who developed AF had higher odds of increase in subclinical cerebral infarctions (odds ratio [OR], 3.08; 95% CI, 1.39–6.83), worsening sulcal grade (OR, 3.56; 95% CI, 1.04–12.2), and worsening ventricular grade (OR, 9.34; 95% CI, 1.24–70.2). In cross-sectional analysis, of 969 participants, 35 (3.6%) had prevalent AF at the time of the 2004 to 2006 MRI scan. Those with AF had greater odds of higher sulcal (OR, 3.9; 95% CI, 1.7–9.1) and ventricular grade (OR, 2.4; 95% CI, 1.0–5.7) after multivariable adjustment and no difference in white matter hyperintensity or total brain volume. Conclusions— AF is independently associated with increase in subclinical cerebral infarction and worsening sulcal and ventricular grade—morphological changes associated with aging and dementia. More research is needed to define the mechanisms underlying AF-related neurodegeneration.


2008 ◽  
Vol 21 (4) ◽  
pp. 500-504 ◽  
Author(s):  
P. Papapostolou ◽  
F. Goutsaridou ◽  
M. Arvaniti ◽  
M. Emmanouilidou ◽  
G. Tezapsidis ◽  
...  

2015 ◽  
Vol 145 (8) ◽  
pp. 1817-1823 ◽  
Author(s):  
Elske M Brouwer-Brolsma ◽  
Nikita L van der Zwaluw ◽  
Janneke P van Wijngaarden ◽  
Rosalie A Dhonukshe-Rutten ◽  
Paulette H in 't Veld ◽  
...  

2015 ◽  
Vol 35 (11) ◽  
pp. 1882-1887 ◽  
Author(s):  
Hazel I Zonneveld ◽  
Elizabeth A Loehrer ◽  
Albert Hofman ◽  
Wiro J Niessen ◽  
Aad van der Lugt ◽  
...  

The question remains whether reduced cerebral blood flow (CBF) leads to brain atrophy or vice versa. We studied the longitudinal relation between CBF and brain volume in a community-dwelling population. In the Rotterdam Study, 3011 participants (mean age 59.6 years (s.d. 8.0)) underwent repeat brain magnetic resonance imaging to quantify brain volume and CBF at two time points. Adjusted linear regression models were used to investigate the bidirectional relation between CBF and brain volume. We found that smaller brain volume at baseline was associated with a steeper decrease in CBF in the whole population (standardized change per s.d. increase of total brain volume (TBV) = 0.296 (95% confidence interval (CI) 0.200; 0.393)). Only in persons aged ≥ 65 years, a lower CBF at baseline was associated with steeper decline of TBV (standardized change per s.d. increase of CBF = 0.003 (95% CI −0.004; 0.010) in the whole population and 0.020 (95% CI 0.004; 0.036) in those aged ≥65 years of age). Our results indicate that brain atrophy causes CBF to decrease over time, rather than vice versa. Only in persons aged >65 years of age did we find lower CBF to also relate to brain atrophy.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9012
Author(s):  
Curtis W. Dewey ◽  
Mark Rishniw ◽  
Philippa J. Johnson ◽  
Emma S. Davies ◽  
Joseph J. Sackman ◽  
...  

Objective Spontaneous brain microhemorrhages in elderly people are present to some degree in Alzheimer’s disease patients but have been linked to brain atrophy in the absence of obvious cognitive decline. Brain microhemorrhages have recently been described in older dogs, but it is unclear whether these are associated with brain atrophy. Diminution of interthalamic adhesion size-as measured on MRI or CT-has been shown to be a reliable indicator of brain atrophy in dogs with canine cognitive dysfunction (CCD) in comparison with successfully aging dogs. We hypothesized that aging dogs with brain microhemorrhages presenting for neurologic dysfunction but without obvious features of cognitive decline would have small interthalamic adhesion measurements, like dogs with CCD, compared with control dogs. The objective of this study was to compare interthalamic adhesion size between three groups of aging (>9 years) dogs: (1) neurologically impaired dogs with presumptive spontaneous brain microhemorrhages and no clinical evidence of cognitive dysfunction (2) dogs with CCD (3) dogs without clinical evidence of encephalopathy on neurologic examination (control dogs). MR images from 52 aging dogs were reviewed and measurements were obtained of interthalamic adhesion height (thickness) and mid-sagittal interthalamic adhesion area for all dogs, in addition to total brain volume. Interthalamic adhesion measurements, either absolute or normalized to total brain volume were compared between groups. Signalment (age, breed, sex), body weight, presence and number of SBMs, as well as other abnormal MRI findings were recorded for all dogs. Results All interthalamic adhesion measurement parameters were significantly (P < 0.05) different between control dogs and affected dogs. Both dogs with cognitive dysfunction (12/15; 80%) and dogs with isolated brain microhemorrhages had more microhemorrhages than control dogs (3/25; 12%). Affected dogs without cognitive dysfunction had significantly more microhemorrhages than dogs with cognitive dysfunction. In addition to signs of cognitive impairment for the CCD group, main clinical complaints for SBM and CCD dogs were referable to central vestibular dysfunction, recent-onset seizure activity, or both. Geriatric dogs with spontaneous brain microhemorrhages without cognitive dysfunction have similar MRI abnormalities as dogs with cognitive dysfunction but may represent a distinct disease category.


2021 ◽  
Author(s):  
Eilidh MacNicol ◽  
Paul Wright ◽  
Eugene Kim ◽  
Irene Brusini ◽  
Oscar Esteban ◽  
...  

Age-specific resources mitigate biases in human MRI processing arising from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue’s relative contribution to total brain volume would change with age in the adult rat. However, the currently available tissue probability maps, which provide a priori information for tissue volume estimation, provide inaccurate grey matter probabilities in subcortical structures, particularly the thalamus. Consequently, age-specific templates and tissue probability maps were generated from a longitudinal study that scanned a cohort of rats at 3, 5, 11, and 17 months old. Mixed-effects models assessed the effect of age on brain, grey matter, white matter, and CSF volumes, and the relative tissue proportions. Grey and white matter volume increased with age, and the tissue proportions relative to total brain volume varied throughout adulthood. Furthermore, we present evidence of a systematic underestimation of thalamic grey matter volume with existing resources, which is mitigated with the use of age-specific tissue probability maps since the derived estimates better matched histological evidence. To reduce age-related biases in image pre-processing, a set of rat brain resources from across the adult lifespan is consequently released to expand the preclinical MRI community’s fundamental resources.


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