Age‐Related Cortical Thickness Reduction in Non‐Demented Down's Syndrome Subjects

Romano, Andrea; Cornia, Riccardo; Moraschi, Marta; Bozzao, Alessandro; Chiacchiararelli, Laura; Coppola, Valeria; Iani, Cristina; Stella, Giacomo; Albertini, G.; Pierallini, A.

doi:10.1111/jon.12259

Cited by 18 publications

(16 citation statements)

References 39 publications

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“…The observed increased brain-PAD supports the idea that the long-term consequences of DS include premature “age-like” changes to the structure of the brain. Previously, studies have shown lower brain volumes or abnormal cortical thickness in DS (Koran et al., 2014, Mullins et al., 2013, Pinter et al., 2001, Romano et al., 2016, Teipel et al., 2004) as well as a correlation between age and brain volume in individuals with DS, not seen in controls (Beacher et al., 2010, Krasuski et al., 2002). While these results have been used to indirectly infer the presence of “accelerated” brain aging in DS, our machine learning method provides a more direct approach of quantifying age-related changes to brain structure, by way of reference to a large lifespan training sample.…”

Section: Discussionmentioning

confidence: 99%

Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline

Cole

Annus

Wilson

et al. 2017

Neurobiology of Aging

118

100

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Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer's disease—factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score. DS participants also underwent [11C]-PiB positron emission tomography (PET) scans to index the levels of cerebral beta amyloid deposition, and cognitive assessment. Mean brain-PAD in DS participants' was +2.49 years, significantly greater than controls (p < 0.001). The variability in brain-PAD was associated with the presence and the magnitude of PiB-binding and levels of cognitive performance. Our study indicates that DS is associated with premature structural brain aging, and that age-related alterations in brain structure are associated with individual differences in the rate of beta amyloid deposition and cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline

Cole

Annus

Wilson

et al. 2017

Neurobiology of Aging

118

100

View full text Add to dashboard Cite

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“…We recognize that there may be a systematic difference in brain volume and composition between our demented and nondemented participants. A recent study suggests that partial volume effects are important when quantifying MRS and that knowing the voxel composition of grey and white matter as well as cerebrospinal fluid can reduce variability in studies that include people with neurodegenerative diseases ( Mato Abad et al, 2014 ) Further, there is an age related decrease in cortical thickness in the cingulate gyrus in nondemented adults with DS, which is more rapid between 20–30 years of age ( Romano et al, 2016 ). This suggests that decreased NAA in our study may reflect partial volume effects and potentially be overestimated On the other hand, MI increases, against a potential decrease in volume and thus may be a conservative estimate.…”

Section: Discussionmentioning

confidence: 99%

1 H-MRS metabolites in adults with Down syndrome: Effects of dementia

Lin

Powell

Caban‐Holt

et al. 2016

NeuroImage: Clinical

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To determine if proton magnetic resonance spectroscopy (1H-MRS) detect differences in dementia status in adults with Down syndrome (DS), we used 1H-MRS to measure neuronal and glial metabolites in the posterior cingulate cortex in 22 adults with DS and in 15 age- and gender-matched healthy controls. We evaluated associations between 1H-MRS results and cognition among DS participants. Neuronal biomarkers, including N-acetylaspartate (NAA) and glutamate-glutamine complex (Glx), were significantly lower in DS patients with Alzheimer's should probably be changed to Alzheimer (without ' or s) through ms as per the new naming standard disease (DSAD) when compared to non-demented DS (DS) and healthy controls (CTL). Neuronal biomarkers therefore appear to reflect dementia status in DS. In contrast, all DS participants had significantly higher myo-inositol (MI), a putative glial biomarker, compared to CTL. Our data indicate that there may be an overall higher glial inflammatory component in DS compared to CTL prior to and possibly independent of developing dementia. When computing the NAA to MI ratio, we found that presence or absence of dementia could be distinguished in DS. NAA, Glx, and NAA/MI in all DS participants were correlated with scores from the Brief Praxis Test and the Severe Impairment Battery. 1H-MRS may be a useful diagnostic tool in future longitudinal studies to measure AD progression in persons with DS. In particular, NAA and the NAA/MI ratio is sensitive to the functional status of adults with DS, including prior to dementia.

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“…Seizures could be a result of the PNH (which contains epileptogenic cells) although patients with 22q11.2DS and no structural abnormalities also have an overall lower seizure threshold . Schizophrenia, OCD and ID have been associated with multiple structural abnormalities, including abnormal cortical thickness and connectivity in the cingulate, prefrontal cortex, olfactory bulb, amongst other regions . Postmortem studies of non‐22q11.2DS schizophrenic brains have also shown decline in GABAergic interneurons most prominently in pre‐frontal and cingulate association cortices .…”

Section: Discussionmentioning

confidence: 99%

Periventricular nodular heterotopia in 22q11.2 deletion and frontal lobe migration

Rezazadeh

Bercovici

Kiehl

et al. 2018

Ann Clin Transl Neurol

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ObjectiveWe aimed to delineate the distribution of periventricular nodular heterotopia (PNH) in patients with 22q11.2 microdeletion syndrome (22q11.2DS) and place this in the context of other genetic forms of PNH.MethodsWe retrospectively analyzed brain imaging and postmortem data available for adult patients with 22q11.2DS. We included only those with good quality MRI data (n = 29) in addition to two patients with PNH identified through postmortem studies. We also reviewed the pattern of PNH in all genetic conditions reported with this phenotype.ResultsOf the total seven patients (M = 4, F = 3; age: 19–61 years) identified to have PNH, six had a history of seizures, six had schizophrenia, six had variable levels of intellectual disability, and two had obsessive compulsive disorder. In all seven patients, the nodules were located over the dorsal pole of the frontal horn of the lateral ventricles. The nodules were small, noncontiguous, and ranged in number from 1 to 10 per individual. Our review identified 37 genetic conditions associated with PNH. With the cases reported here, 22q11.2DS becomes the fifth most commonly reported genetic condition, and the third most common copy number variation, associated with PNH.InterpretationThe neuropsychiatric manifestations in our patients with PNH support other data indicating abnormal neurodevelopment as part of the pathogenesis of 22q11.2DS.The location and cellular characteristics of PNH in 22q11.2DS overlaps with a group of migrating postnatal interneurons termed Arc cells, although more research is needed to confirm that PNH in 22q11.2DS represents Arc cells arrested in their migratory pathway.

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Age‐Related Cortical Thickness Reduction in Non‐Demented Down's Syndrome Subjects

Abstract: Our findings showed that Down Syndrome subjects are affected by a diffuse cortical thinning. The involvement of cortical structures can be observed at an earlier age than previous studies have reported.

Cited by 18 publications

References 39 publications

Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline

Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline

1 H-MRS metabolites in adults with Down syndrome: Effects of dementia

Periventricular nodular heterotopia in 22q11.2 deletion and frontal lobe migration

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