We searched PubMed, Medline, and PsycNET Direct (1970 to December 2009). We used the search terms “Down's syndrome” or “mental retardation” or “cognitive impairment” in combination with the words “genomic imbalance”, “gene–environment interactions”, “mothering style”, “endophenotypes”, “trisomy”, “language”, “morphosyntax”, “verbal short-term memory”, “explicit memory”, “implicit memory”, “associative learning”, “executive function”, “visuospatial abilities”, “avoidance strategies”,
ReviewCognitive deficits and associated neurological complications in individuals with Down's syndrome
Introduction
Down's syndrome has an incidence of about one in 650–1000 livebirths worldwide.1 The disorder is caused by trisomy of chromosome 21 and is associated with many neurological complications, including cognitive deficits, seizures, early-onset dementia that resembles Alzheimer's disease, and neurological complications of systemic disorders. Medical interventions in Down's syndrome have resulted in increased longevity, with the estimated life expectancy of people with Down's syndrome in developed countries increasing from an average of 12 years in the 1940s to an average of 57·8 years for women and 61·1 years for men.1, 2 The symptomatic onset of some neurological complications in people with Down's syndrome is age-specific; therefore, because certain complications will arise in childhood and others in adulthood, their occurrence is relevant to paediatric and adult neurologists. In this review we provide a critical overview of cognitive functioning in individuals with Down's syndrome and discuss how cognitive functioning is affected by neurological complications in children and adults.
Section snippets
Pathogenesis
The relation between genomic effects of the trisomy that causes Down's syndrome and pathogenetic mechanisms underlying cognitive deficits are not fully understood, in part because of the broad variability of the phenotypic effects of the disorder. This variability might be caused by allelic variation, genomic imbalance, or epigenetic or environmental factors,3, 4, 5, 6, 7, 8, 9 and therefore homologous structural changes in the brain do not affect all individuals with Down's syndrome in the
Seizures
Seizures occur in a bimodal distribution in Down's syndrome, with 40% of people with the disorder having seizure onset before 1 year of age and another 40% having seizure onset in the third decade of life or later.66 Seizures can impair cognitive functioning, particularly if uncontrolled. Insights from mouse models in which frequent seizures are induced have implicated aberrant sprouting of nerve fibres, reduced neurogenesis, and abnormal neurotransmitter function.67, 68 In a
Dementia that resembles Alzheimer's disease
By age 40 years, almost all individuals with Down's syndrome have characteristics of Alzheimer's disease, such as plaques and tangles (figure 2). Amyloid accumulation in the brain starts in the childhood years, thereby linking development with brain ageing in the disorder.90 Concentrations of brain amyloid increase markedly after age 45 years and are associated with the presence of neurofibrillary tangles.91 There are a number of genes present on chromosome 21 that have been implicated in
Neurological complications of systemic disorders
A prospective cohort study reported that 57% of children aged 2–4 years who had Down's syndrome had obstructive sleep apnoea,116 a condition that is associated with lower IQ and behavioural disorders.117, 118 In Down's syndrome, the number of apnoeas is associated with difficulties in visuoperceptual skills, particularly those involving the right hemisphere.119 Sleep apnoea is associated with several otolaryngologic problems in children and adults with Down's syndrome, including otitis media,
Psychiatric comorbidities
Severe psychiatric and behavioural problems are rare in children with Down's syndrome, but there is an increased risk of depression in adults with the disorder compared with the general population.135 In childhood, behaviours that can interfere with adaptive functioning include stubbornness, oppositionality, and inattention.135 There seems to be a comorbidity between Down's syndrome and autism, with prevalence rates suggesting that ten-times more children with Down's syndrome have symptoms of
Vascular disease and stroke
Individuals with Down's syndrome have a low prevalence of coronary artery disease and rarely die of complications related to atherosclerosis despite having a tendency towards obesity and abnormal lipid profiles associated with risk of cardiovascular disease.143 Histopathological examination of the arterial system in Down's syndrome has shown either an absence or a low level of atherosclerosis.144, 145 This absence of atherosclerosis in the disorder is an interesting feature which remains
Concluding remarks
Cognitive deficits in people with Down's syndrome are not linear; rather, they are characterised by variability in several aspects of learning and memory. Therefore, vigilance is required in recognising and treating the complications of Down's syndrome that can impair cognition. Future research is needed to investigate the following associations with Down's syndrome: age-dependent susceptibility to seizures and prognosis; optimum therapeutic approach for treating thyroid problems to protect
Search strategy and selection criteria
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