Learning and memory as a function of age in Down syndrome: A study using animal-based tasks

Nelson, Linda D.; Johnson, Julene K.; Freedman, Morris; Lott, Ira T.; Groot, Jantje; Chang, Marisa; Milgram, Norton W.; Head, Elizabeth

doi:10.1016/j.pnpbp.2004.12.009

Cited by 54 publications

(39 citation statements)

References 43 publications

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“…While the measure of 'frontal function' used in this study is somewhat crude, two further studies provide support for the early compromise of frontal lobe associated cognitive functions in dementia in DS. Das and Mishra (1995), suggest that impairments in planning may occur in the early stages of dementia and a recent study by Nelson et al (2005) suggests that performance on frontal lobe associated tasks, developed for use in animal studies, is related to both age and the presence of dementia.…”

Section: Discussionmentioning

confidence: 99%

Personality and behaviour changes mark the early stages of Alzheimer's disease in adults with Down's syndrome: findings from a prospective population-based study

Ball

Holland

Hon

et al. 2006

Int. J. Geriat. Psychiatry

157

148

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These findings confirm that the early presentation of AD in DS is characterized by prominent personality and behaviour changes, associated with executive dysfunction, providing support for the notion that the functions of the frontal lobes may be compromised early in the course of the disease in this population. This has important implications for the diagnosis, treatment and management of dementia in people with DS.

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Section: Discussionmentioning

confidence: 99%

Personality and behaviour changes mark the early stages of Alzheimer's disease in adults with Down's syndrome: findings from a prospective population-based study

Ball

Holland

Hon

et al. 2006

Int. J. Geriat. Psychiatry

157

148

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“…The impaired intellectual function in DS is caused by abnormalities in memory, language and learning [21]. Morphosyntax, verbal short-term memory and explicit long-term memory are typically affected by memory and language abilities.…”

Section: Introductionmentioning

confidence: 99%

Structural brain alterations of Down’s syndrome in early childhood evaluation by DTI and volumetric analyses

et al. 2016

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Objectives To provide an initial assessment of white matter (WM) integrity with diffusion tensor imaging (DTI) and the accompanying volumetric changes in WM and grey matter (GM) through volumetric analyses of young children with Down's syndrome (DS). Methods Ten children with DS and eight healthy control subjects were included in the study. Tract-based spatial statistics (TBSS) were used in the DTI study for whole-brain voxelwise analysis of fractional anisotropy (FA) and mean diffusivity (MD) of WM. Volumetric analyses were performed with an automated segmentation method to obtain regional measurements of cortical volumes. Results Children with DS showed significantly reduced FA in association tracts of the fronto-temporo-occipital regions as well as the corpus callosum (CC) and anterior limb of the internal capsule (p < 0.05). Volumetric reductions included total cortical GM, cerebellar GM and WM volume, basal ganglia, thalamus, brainstem and CC in DS compared with controls (p < 0.05). Conclusion These preliminary results suggest that DTI and volumetric analyses may reflect the earliest complementary changes of the neurodevelopmental delay in children with DS and can serve as surrogate biomarkers of the specific elements of WM and GM integrity for cognitive development. Key Points• DS is the most common genetic cause of intellectual disability.• WM and GM structural alterations represent the neurological features of DS.• DTI may identify the earliest aging process changes.• DTI-volumetric analyses can serve as surrogate biomarkers of neurodevelopment in DS.

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“…Down syndrome (DS, trisomy 21), the most common genetic cause of mental retardation, is characterized by decreased brain size, language, and memory deficits and other cognitive abnormalities (Haxby, 1989;Raz et al, 1995;Brock and Jarrold, 2005;Nelson et al, 2005). The cognitive impairment that characterizes DS subjects is thought to be related to the reduction in overall brain size, volume of various brain regions and cortical neuron density (Sylvester, 1983;Ross et al, 1984;Coyle et al, 1986;Schapiro et al, 1989;Aylward et al, 1997Aylward et al, , 1999.…”

Section: Introductionmentioning

confidence: 99%

Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with down syndrome and in Ts65Dn mice

et al. 2007

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Down syndrome (DS), the leading genetic cause of mental retardation, is characterized by reduced number of cortical neurons and brain size. The occurrence of these defects starting from early life stages points at altered developmental neurogenesis as their major determinant. The goal of our study was to obtain comparative evidence for impaired neurogenesis in the hippocampal dentate gyrus (DG) of DS fetuses and Ts65Dn mice, an animal model for DS. Cell proliferation in human fetuses was evaluated with Ki-67 (a marker of cells in S + G(2) + M phases of cell cycle) and cyclin A (a marker of cells in S phase) immunohistochemistry. We found that in the DG of DS fetuses the number of proliferating cells was notably reduced when compared with controls. A similar reduction was observed in the germinal matrix of the lateral ventricle. In both structures, DS fetuses showed a reduced ratio between cyclin A- and Ki-67-positive cells when compared with controls, indicating that they had a reduced number of cycling cells in S phase. In the DG of P2 Ts65Dn mice cell proliferation, assessed 2 h after an injection of bromodeoxyuridine (BrdU), was notably reduced, similarly to DS fetuses. After 28 days, Ts65Dn mice had still less BrdU-positive cells than controls. Phenotypic analysis of the surviving cells showed that Ts65Dn mice had a percent number of cells with astrocytic phenotype larger than controls. Using phospho-histone H3 immunohistochemistry we found that both DS fetuses and P2 Ts65Dn mice had a higher number of proliferating cells in G(2) and a smaller number of cells in M phase of cell cycle. Results provide novel evidence for proliferation impairment in the hippocampal DG of the DS fetal brain, comparable to that of the P2 mouse model, and suggest that cell cycle alterations may be critical determinants of the reduced proliferation potency.

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Learning and memory as a function of age in Down syndrome: A study using animal-based tasks

Cited by 54 publications

References 43 publications

Personality and behaviour changes mark the early stages of Alzheimer's disease in adults with Down's syndrome: findings from a prospective population-based study

Personality and behaviour changes mark the early stages of Alzheimer's disease in adults with Down's syndrome: findings from a prospective population-based study

Structural brain alterations of Down’s syndrome in early childhood evaluation by DTI and volumetric analyses

Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with down syndrome and in Ts65Dn mice

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