Down syndrome with and without dementia: An in vivo proton Magnetic Resonance Spectroscopy study with implications for Alzheimer's disease

Lamar, Melissa; Foy, Catherine; Beacher, Felix; Daly, Eileen; Poppe, Michaela; Archer, Nicola; Murphy, Kieran C.; Morris, Robin G.; Simmons, Andrew; Lovestone, Simon; Murphy, Declan

doi:10.1016/j.neuroimage.2011.03.073

Cited by 30 publications

(33 citation statements)

References 36 publications

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“…Therefore, the group differences found in regional brain volume between DS+ and AD in the general population most probably reflect AD-type neuropathology. The sample in this study was characterized with AD using identical methods to those previously reported and accepted for publication by other high impact factor journals [5,9,36]. …”

Section: Discussionmentioning

confidence: 99%

“…We have previously reported [5] that subjects with DS who do not have dementia (DS-) have a significant increase in the concentration of mI as compared to controls, and that increased mI is associated with reduced overall cognitive ability (including memory). People with DS and dementia (DS+) have higher mI concentration than those without dementia (DS-), or people from the general population who have AD or mild cognitive impairment [8,9]. …”

Section: Introductionmentioning

confidence: 99%

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Dementia in Down’s syndrome: an MRI comparison with Alzheimer’s disease in the general population

Mullins

Daly²,

Simmons

et al. 2013

J Neurodevelop Disord

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BackgroundDown’s syndrome (DS) is the most common genetic cause of intellectual disability. People with DS are at an increased risk of Alzheimer’s disease (AD) compared to the general population. Neuroimaging studies of AD have focused on medial temporal structures; however, to our knowledge, no in vivo case–control study exists comparing the anatomy of dementia in DS to people with AD in the general population. We therefore compared the in vivo brain anatomy of people with DS and dementia (DS+) to those with AD in the general population.MethodUsing MRI in 192 adults, we compared the volume of whole brain matter, lateral ventricles, temporal lobes and hippocampus in DS subjects with and without dementia (DS+, DS-), to each other and to three non-DS groups. These included one group of individuals with AD and two groups of controls (each age-matched for their respective DS and general population AD cohorts).ResultsAD and DS+ subjects showed significant reductions in the volume of the whole brain, hippocampus and temporal lobes and a significant elevation in the volume of the lateral ventricle, compared to their non-demented counterparts. People with DS+ had a smaller reduction in temporal lobe volume compared to individuals with AD.ConclusionsDS+ and AD subjects have a significant reduction in volume of the same brain regions. We found preliminary evidence that DS individuals may be more sensitive to tissue loss than others and have less ‘cognitive reserve’.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dementia in Down’s syndrome: an MRI comparison with Alzheimer’s disease in the general population

Mullins

Daly²,

Simmons

et al. 2013

J Neurodevelop Disord

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“…MRS can quantify the concentration of a number of metabolites which serve as biomarkers for brain health including: total N‐acetyl‐aspartate (tNAA, plays a role in myelin synthesis, reflects neuronal integrity), total creatine (tCr, creatine and phosphocreatine, phosphorylated at the outer membrane of mitochondria, a marker of mitochondrial density or function), total choline (tCho, choline‐containing compounds, indicative of membrane turnover and/or synthesis), glutamate and glutamine (Glu + Gln = Glx, Glu: neurotransmitter, Gln: Glu uptake, both Glu and Gln are indicators of synapse density), and myoinositol (mI, glial marker, indicative of gliosis and scarring) . MRS can successfully be implemented to study the hippocampus in neurodegenerative diseases . Previous work has demonstrated that reductions in hippocampal NAA can be detected in subjects with mild cognitive impairment, and that hippocampal NAA and tCR can distinguish between mild Alzheimer's disease and normal elderly controls …”

Section: Introductionmentioning

confidence: 99%

Longer Repetition Time Proton MR Spectroscopy Shows Increasing Hippocampal and Parahippocampal Metabolite Concentrations with Aging

Sporn

MacMillan

et al. 2019

Journal of Neuroimaging

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BACKGROUND AND PURPOSE Previous magnetic resonance spectroscopy (MRS) studies have concluded that hippocampal and parahippocampal metabolite concentrations remain stable during healthy adult aging. However, these studies used short repetition times (TR ≤ 2 seconds), which lead to incomplete longitudinal magnetization recovery, and thus, heavily T1‐weighted measurements. It is important to accurately characterize brain metabolites changes with age to enable appropriate interpretations of MRS findings in the context of neurodegenerative diseases. Our goal was to assess hippocampal brain metabolite concentrations in a large cohort of diversely aged healthy volunteers using a longer TR of 4 seconds. METHODS Left hippocampal MR spectra were collected from 38 healthy volunteers at 3T. Absolute metabolite concentrations were determined for total N‐acetyl‐aspartate (tNAA), total creatine (tCr), total choline (tCho), glutamate and glutamine (Glx), and myoinositol (mI). Individual partial correlations between each metabolite with age were assessed using demographic information and voxel compartmentation as confounders. RESULTS Hippocampal tNAA, tCr, tCho, and mI all increased with age (NAA: R2 = .17, P = .041; tCr: R2 = .45, P = .0002; tCho: R2 = .37, P = .001; mI: R2 = .44, P = .0003). There were no relationships between age and signal to noise ratio, linewidth, or scan date, indicating the correlations were not confounded by spectral quality. Furthermore, we did not observe a trend with age in the voxel tissue compartmentations. CONCLUSIONS We observed increases in hippocampal/parahippocampal metabolite concentrations with age, a finding that is in contrast to previous literature. Our findings illustrate the importance of using a sufficiently long TR in MRS to avoid T1‐relaxation effects influencing the measurement of absolute metabolite concentrations.

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“…Magnetic resonance spectroscopic differences include an elevated myoinositol peak in subjects with Down Syndrome, with (Lamar et al, 2011) or without (Beacher et al, 2005) dementia, but without changes in creatine or N-acetylaspartate (Shonk and Ross, 1995). An activation study using magnetoencephalography (MEG) indicated that different subjects with Down Syndrome may differ in the ipsilateral vs. contralateral response to a finger movement task (Virji-Babul et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Abnormal brain synchrony in Down Syndrome

Anderson

Nielsen

Ferguson

et al. 2013

NeuroImage: Clinical

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142

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Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks.

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Down syndrome with and without dementia: An in vivo proton Magnetic Resonance Spectroscopy study with implications for Alzheimer's disease

Cited by 30 publications

References 36 publications

Dementia in Down’s syndrome: an MRI comparison with Alzheimer’s disease in the general population

Dementia in Down’s syndrome: an MRI comparison with Alzheimer’s disease in the general population

Longer Repetition Time Proton MR Spectroscopy Shows Increasing Hippocampal and Parahippocampal Metabolite Concentrations with Aging

Abnormal brain synchrony in Down Syndrome

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