Ageing in higher functioning adults with Down's syndrome: an interim report in a longitudinal study

ABSTRACT. Mildly and moderately mentally retarded adults, who live in the community, were examined for global changes in mental status and specific changes in auditory and visual memory over a period of 3–5 years. Twenty-eight subjects with Down's syndrome (DS) between the ages of 27 arid 55 years were compared to 18 subjects without DS who were of similar IQ and age. The evaluation of mental status consisted of testing orientation to person, place and time, object naming, visuomotor coordination, and concentration. Auditory memory was tested with an adapted version of the Buschke Memory test. Visual memory testing consisted of matching shapes which were presented simultaneously and after delays of 0, 5 and 10s on a computer-controlled screen. No changes were found in test scores between an initial testing and follow-up testing up to 5 years later, indicating that ageing processes were not having a major impact in the cognitive functioning of these subjects. Furthermore, there was no indication of any generalized decline in performance suggestive of early symptoms of dementia among the older subjects with DS.     

Manual and oral praxis in adults with Down's syndrome

Mentally handicapped adults with and without Down's syndrome performed single movements and movement sequences following both verbal and demonstration cueing conditions. While the type of cue did not influence the performance of control subjects. Down's syndrome individuals exhibited more error following verbal cueing. These findings could not be explained on the basis of verbal encoding differences between the groups. The results support the notion that Down's syndrome persons suffer from a dissociation of the functional system responsible for speech perception and the system involved with the organization of complex movement.     

Nocturnal periodic breathing in adults with Down's syndrome

ABSTRACT. Nineteen adults with Down's syndrome were studied with the static charge sensitive bed (SCSBl method. A single whole-night recording was made of each subject. Two different periodic breathing indices (PBIf and PBI%) were calculated from a computerized analysis of these recordings. A polygraphic recording was also made of one subject, a 52-year-old male. The EEC, the EOG, the EMG, nasal and oral airflow, and diaphragmatic movement were recorded, the latter with an abdominal strain gauge and with the SCSB-method simultaneously. Good correlation was found between the recording with the SCSB and the strain gauge. The apnoea index (AI calculated from the polygraphic recording was 23.3, while the PBIf of this patient recorded on another night and analysed automatically was 45 and the PBI% was 78.6. The patient group was divided into those aged 40 or older (n= 10) and those aged 39 or younger (n=9). The mean PBI% of the older group was 24.0 while that of the younger group was 5.4 (t = 2.23; P<0.05). The mean PBIf of the older group was 16.7 and that of the younger was 3.6 (i=2.70; P=<0.02). The mean body mass index (BMI) of the younger group was significantly higher than the mean BMI of the older group. The mean BMI of those patients, whose FBI values were considered to be normal (PBI% <3, PBIf <7), did not significantly differ from the BMI of those patients, whose PBI-values were abnormal. There were four patients with tonsillar or lingual hypertrophy in the older age group and five in the younger. The mean FBI-values between those with and those without narrowing of the upper airways did not differ significantly. The study thus indicated that age is the most significant factor favouring the development of periodic breathing during sleep in patients with Down's syndrome.     

Working memory and everyday cognition in adults with Down's syndrome

A number of previous studies have suggested that young people with Down's syndrome (DS) have a specific deficit of the phonological loop component of the working memory. However, there have also been studies which have proposed a specific deficit of the central executive component of working memory and suggested similarities of working memory functioning with patients with Alzheimer's disease. Fifteen middle‐aged people with DS were matched for their individual scores of non‐verbal intelligence to 15 individuals with mixed aetiology of intellectual disability. A versatile range of tasks was used in order to evaluate the functioning of working memory components. In addition, several everyday cognition skills were assessed. The subjects with DS performed significantly more poorly in all tasks assessing the phonological loop. Performance in other working memory tasks and compound variables representing different working memory components was equal in the groups. In addition, both groups had equal everyday cognition skills. The functioning of the phonological loop seems to be clearly deficient in people with DS. Interestingly, the deficit does not seem to affect the vocabulary or other everyday cognition skills in individuals with DS. No signs of specific deficit of the central executive component of working memory were found.     

Cervical spine abnormalities in institutionalized adults with Down's syndrome

ABSTRACT. The prevalence of increased anterior atlanto-odontoid distance (AAOD), a risk factor for spinal cord compression, and degenerative disease of the cervical spine (DDCS) in a population of institutionalized adults with Down's syndrome (DS) was determined and compared with age- and sex-matched'normals'presenting to a hospital emergency department. Radiographs of the cervical spines of 99 adults with DS and 198'normals'were compared using a standardized rating scale. The prevalence of an AAOD of 3 mm or greater, the threshold of risk from the literature, was 8% for DS cases and 2% for controls (P<0.01). The mean AAOD for DS cases was 2.0±l mm and for controls l.5±0.5 mm (P<0.01). There was a negative correlation between AAOD and age of DS cases. The prevalence of any degree of DDCS among the DS cases was 64%, the controls 39% (P<0.001); for moderate or severe DDCS the prevalence among DS cases was 45%, controls 12% (P<0.001). The prevalence of DDCS increased with age in both groups, but the severity of DDCS was significantly greater for DS individuals in all age groups. The levels of the cervical spine affected ranged from C2 to C6; the most commonly affected level was C5-C6. While DS adults are at increased theoretical risk for spinal cord compression due to increased AAOD, its clinical significance would appear to be small and to decline with age. Of more concern is the high prevalence of DDCS; adults with DS are at high risk for this condition and consideration should be given to this diagnosis in the appropriate clinical setting.     

Overweight and obesity amongst Down's syndrome adults

Two hundred and one individuals with Down's syndrome were assessed for evidence of overweight and obesity. Thirty-one per cent of males and 22% of females were overweight, while 48% males and 47% females were obese. Overweight and obesity was significantly associated with living in the family home compared to supervised community units or in hospital. No association with the degree of learning disability vras found.     

Brain-stem auditory evoked potentials in adults with Down's syndrome.

Brain-stem auditory evoked potentials (BAEPs) were examined in 37 adult patients with Down's syndrome and in 37 age-matched normal subjects. All absolute and interpeak latencies except for the interpeak latency IV-V were shorter in patients than in normal subjects. The amplitude of wave V and the amplitude ratio V/I were smaller in patients than in normal subjects. Short latencies in patients were considered to be due to the smaller size of the brain-stem or to faster conduction velocity. The prolonged interpeak latency IV-V and the smaller wave V may indicate physiological dysfunctions between the upper pons and the lower midbrain.     

Sequence of cognitive decline in dementia in adults with Down's syndrome

Adults with Down's syndrome (DS) are known to be at risk of dementia of the Alzheimer type (DAT), but because of their lifelong intellectual deficits, it is difficult to determine the earliest signs and characteristics of age‐associated decline and dementia. In a longitudinal study in which all participants were healthy at the time of their entry into the study, the present authors compared the amount of decline on the subtests of the WISC‐R to determine the sequence of cognitive decline associated with varying stages of dementia. Twenty‐two individuals with varying degrees of cognitive decline were compared to 44 adults with DS who have remained healthy. All participants functioned in the mild or moderate range of intellectual disability at initial testing. On each subtest of the WISC‐R, the amount of change experienced by the healthy participants over the study period was compared to the amount of change found for each of the groups with decline. Out of the individuals who showed declines, 10 adults with DS were classified as having ‘questionable’ decline based on the presence of memory impairment, and five and seven adults with DS were classified as in the ‘early stage’ and ‘middle stage’ of DAT, respectively, based on the presence of memory impairment, score on the Dementia Scale for Down Syndrome and a physician's diagnosis. It was found that participants who were identified as ‘questionable’, in addition to the memory loss that determined their classification, also showed significant declines on the Block Design and Coding subtests. The five adults in the early stage of dementia showed declines on these subtests, and in addition, on the Object Assembly, Picture Completion, Arithmetic and Comprehension subtests. The seven adults in the middle stage of dementia showed declines on these subtests, plus declines on Information, Vocabulary and Digit Span subtests. The Picture Arrangement and Similarities subtests were not useful in distinguishing between the groups because of baseline floor effects for a substantial proportion of participants. The present longitudinal study showed a sequence of cognitive decline associated with DAT, beginning with a possible ‘pre‐clinical’ stage, and progressing through the early and middle stages. This approach begins to define the sequence of declining cognitive capacities that contributes to the observed functional deterioration caused by Alzheimer's disease and that is likely to reflect the involvement of cortical areas as the disease progresses.     

Basal metabolic rate in healthy Down's syndrome adults

ABSTRACT. Basal metabolic rale (BMR) was measured on 2 consecutive Jays with an open-circuit, indirect calorimeter in 16 healthy subjects with trisomy 21 Down's syndrome (DS) aged 22-35 years and 11 healthy control volunteers aged 20-31 years. BMR measurements Jut mil differ on consecutive days in either the DS or control groups. Absolute BMR, BMR corrected for surface area, and HMR corrected tor lean body mass did not differ between the DS subjects and the volunteers. The per cent of predicted BMR also did not Jitter between the two groups. These results suggest that systems controlling basal metabolism are not affected by extra gcnomic material from chromosome 21.     

Normal ageing in adults with Down's syndrome: a longitudinal study

The ubiquitous presence of the neuropathoiogy of Alzheimer disease (AD) in individuals with Down's syndrome (DS) over 40 years of age suggests that this group of people will exhibit a high prevalence of dementia of the Alzheimer type (DAT) as they age. The present study indicates that there is a clear discrepancy between the presumed presence of AD neuropathoiogy and the clinical expression of DAT among older people with DS. In the first 6 years of a longitudinal study, the present authors compared 91 adults (31–63 years of age) with DS and mild or moderate mental retardation to 64 adults (3 l –76 years of age) with other forms of mental retardation (MR) on yearly measures of mental status, short-and long-term memory, speeded psychomotor function, and visuospatial organization. The results indicated that, over repeated testing on the verbal long–term memory test, younger participants with DS showed small increases in their scores, while older participants with DS showed very slight decreases. Overall performance scores on this test and a speeded psychomotor task were poorer for both diagnostic groups in individuals aged SO years and older. The magnitude and type of these selective changes in performance were consistent with performance profiles observed in older healthy adults without mental retardation on tests measuring similar cognitive functions. Only four out of the 91 people with DS in the present sample showed changes in funaioning that have led to a diagnosis of possible DAT. and in these individuals, alternative causes of performance declines were concurrently present (e.g, thyroid dysfunction). These findings indicate that some age–associated changes in funaioning are related to ‘normal’ but probably precocious ageing among adults with DS. Furthermore, these findings suggest that adults with DS and mild or moderate mental retardation may be at lower risk for dementia during their fourth and fifth decades of life than previous studies have suggested.     

Cerebrospinal fluid monoaminergic metabolites are elevated in adults with Down's syndrome

Under conditions of rest and a low monoamine diet, brain monoamine activity was examined in young (less than 35 years) and old (greater than 35 years) adults with Down's syndrome and in control subjects by measuring the cerebrospinal fluid (CSF) and plasma concentrations of the neurotransmitter norepinephrine, and of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy 4-hydroxyphenylglycol (MHPG), the respective metabolites of the neurotransmitters serotonin, dopamine, and norepinephrine. There were no age-related differences in metabolite concentrations in either the Down's syndrome or control subjects. CSF concentrations of 5-HIAA, HVA, and norepinephrine were significantly higher in young subjects with Down's syndrome as compared with young controls, and CSF concentrations of 5-HIAA and norepinephrine were significantly higher, by twofold or more, in old subjects with Down's syndrome as compared with older controls. The results suggest that monoamine turnover and brain functional activity involving monoamines is elevated in Down's syndrome, and that the early neuropathological changes in the disorder are not associated with a monoamine deficit.     

Speaking fundamental frequency characteristics of institutionalized adults with Down's syndrome.

Mean speaking fundamental frequency was obtained from 16 institutionalized adults with Down's syndrome (8 males, 8 females) and from 16 nonretarded adults of similar age and sex. Both male and female adults with Down's syndrome exhibited a higher mean speaking fundamental frequency than did the nonretarded adults of the same sex. This finding does not support early reports of a characteristically low-pitched voice among Down's syndrome individuals.     

Neuropsychological evaluation of adults with Down's syndrome: patterns of selective impairment in non-demented old adults

A batiery of neuropsychological tests, developed to study patterns of age-related differences in adults with Down's syndrume (DS), was administered to 10 DS adults over age 35 and 19 younger DS adults. Although all adults with DS are reported to develop the neuropathoiogical changes of Alzheimer's disease by the fourth decade of life, only four of the 10 old DS adults were judged to have dementia based on clinical criteria. Demented old DS adults had global neuropsychological deficits, as indicated by significant differences on all functions tested except some simple language functions. In contrast, non-demented old adults had a selective pattern of neuropsychological reductions relative to young adults. Ability to form new long-term memories and visuospatial construction were consistently diminished, whereas immediate memory span and language were not. The global mental decline observed in demented adults suggests a stage of disease progression that corresponds to severe dementia in pre- morbidly normal adults with dementia of the Alzheimer type (DAT). The prominent long-term memory impairment with selective reductions of nonmemory functions in non-demented adults suggests a correspondence to early and intermediate DAT.     

Maladaptive behaviours and symptoms of dementia in adults with Down's syndrome compared with adults with intellectual disability of other aetiologies

Dementia commonly occurs in elderly people with intellectual disability, especially those with Down's syndrome. The non-cognitive symptoms of dementia can be of greater significance to individuals and carers than the cognitive changes caused by this condition. It is not known whether there are differences between people with Down's syndrome and those with intellectual disability of other causes with regard to the prevalence of such symptoms. The present study was undertaken to draw a comparison between a group with Down's syndrome and dementia ( n = 19), and a group with intellectual disability of other causes and dementia ( n = 26). Maladaptive behaviours and psychiatric symptomatology were assessed in both groups. The group with Down's syndrome had a higher prevalence of low mood, restlessness/excessive overactivity, disturbed sleep, being excessively uncooperative and auditory hallucinations. Aggression occurred with greater frequency in those subjects with intellectual disability of other causes. These findings are of epidemiological importance in terms of service planning and understanding psychiatric presentation.     

MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia

OBJECTIVE: This study sought to determine whether volumes of the hippocampus and amygdala are disproportionately smaller in subjects with Down's syndrome than in normal comparison subjects and whether volume reduction is greater in Down's syndrome subjects with dementia. METHOD: The subjects were 25 adults with Down's syndrome (eight with dementia) and 25 cognitively normal adults who were individually matched on age, sex, and race. Magnetic resonance imaging measures included volumes of the hippocampus, amygdala, and total brain. Nineteen of the Down's syndrome subjects had follow-up scans (interscan interval = 9-41 months). RESULTS: Nondemented Down's syndrome subjects had significantly smaller volumes of the hippocampus, but not the amygdala, than their comparison subjects, even when total brain volume was controlled for. Volumes of both the hippocampus and the amygdala were smaller in the demented Down's syndrome subjects than in their comparison subjects, even when total brain volume was controlled for. Age was not correlated with volume of the hippocampus or amygdala among the nondemented Down's syndrome subjects and the comparison subjects; age was correlated with volume of the amygdala, but not the hippocampus, among the Down's syndrome subjects with dementia. Changes in volume over time were not statistically significant for either the demented or the nondemented subjects. CONCLUSIONS: Hippocampal volume, while disproportionately small for brain size in individuals with Down's syndrome, remains fairly constant through the fifth decade of life in those without dementia. All subjects over age 50 who had Down's syndrome demonstrated volume reduction in the hippocampus as well as clinical signs of dementia. Dementia was also associated with volume reductions in the amygdala that exceeded reductions in total brain volume.