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.     

The Prudhoe Cognitive Function Test, a scale to assess cognitive function in adults with Down's syndrome: inter-rater and test–retest reliability

Background The Prudhoe Cognitive Function Test (PCFT) was designed to measure cognitive function in subjects with all degrees of intellectual disability (ID) and to be administered by non‐specialist raters. The aim of the present study was to measure the test–retest and inter‐rater reliability of the PCFT. Methods Three raters, one a specialist and two non‐specialists, administered the PCFT to 14 subjects with Down's syndrome on two occasions separated by 4 weeks. Results The intra‐class correlation coefficients (ICCs) between the rater pairs (n = 3) were 0.99, 0.99 and 0.98 (P < 0.01). Floor effects were recorded for two items. The ICC for test–retest reliability was 0.99 (P < 0.01). Conclusions The PCFT is a highly reliable instrument when used by either specialist or non‐specialist raters. It has excellent temporal stability.     

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.     

Age at onset of dementia and age of menopause in women with Down's syndrome

Menstrual status and the age of menopause were investigated in 143 Irish females with Down's syndrome (DS). The average age of menopause in 42 subjects (44.7 years) was younger than in the general population. The age at onset of dementia correlated with the age of menopause. This finding may be a manifestation of accelerated ageing in DS or point to oestrogen deficiency being an independent risk factor for the development of Alzheimer's dementia in DS. The implications of this finding for possible treatments are discussed.     

Alzheimer dementia in Down's syndrome: the relevance of cognitive ability

More years of education have been found to be associated with a lower rate of Alzheimer disease (AD) in individuals without intellectual disability. It has been proposed that education reflects greater ‘synaptic reserve’ and that greater synaptic reserve may defer the development of AD. The present study compared individuals with Down's syndrome (DS) who were found to have symptoms of dementia with those who remained symptom‐free to determine if the two groups differed in their level of education, employment, recreational activities, years in an institution or overall level of cognitive functioning. Thirty‐five adults with DS aged between 29 and 67 years were assessed. The participants were recruited from a community health facility and included individuals with a wide range of ability levels. Neuropsychological testing, caregiver report and the Dementia Scale for Down Syndrome ( Gedye 1995 ) were used to identify decline in participants over periods of 6 months to 3 years. After the effect of age was statistically removed, multiple regression analyses revealed that level of cognitive functioning was significantly associated with decline such that a higher level of cognitive functioning predicted less decline. None of the environmental variables (i.e. educational level, years in an institution and employment) were directly associated with decline; however, a post hoc regression using level of cognitive functioning as the outcome variable revealed that level of cognitive functioning itself was associated with these environmental variables. A higher level of cognitive functioning was associated with fewer cases of dementia in individuals with DS, and level of cognitive functioning appears to be associated with environmental factors such as level of education, years in an institution and employment. The present findings suggest that environmental interventions aimed at improving level of cognitive functioning may also be useful in deferring the onset of dementia.     

Use of electroencephalography to detect Alzheimer's disease in Down's syndrome

We studied the role of electroencephalography (EEG) in the diagnosis of Alzheimer-type dementia in patients with Down's syndrome. 197 patients with Down's syndrome were monitored for 5 to 8 years. Aspects of cognitive functioning were assessed twice yearly. EEGs were scored in a blind fashion, and changes in the EEG were compared to changes in cognitive functioning. When possible, a neuropathological post-mortem examination was performed. Cognitive functioning was drastically reduced in 29 patients. The dominant occipital rhythm became slower at the onset of the cognitive deterioration, and eventually disappeared. In 11 of these patients neuropathological examination showed a severe form of Alzheimer's disease. Changes in the frequency of the dominant occipital rhythm could distinguish between Alzheimer's disease or other causes as underlying the cognitive decline. Slowing of the dominant occipital rhythm seems to be related to Alzheimer's disease in patients with Down's syndrome, and the frequency of the dominant occipital activity decreases at the onset of cognitive deterioration. The EEG is thus an important tool in the clinical diagnosis of Alzheimer-type dementia 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.     

Mastery motivation in young children with Down's syndrome: relations with cognitive and adaptive competence

Background Prior research on relations between motivation and competence have focused on cognitive competence, despite theoretical predictions that mastery motivation spurs behaviour that is effective in meeting the demands of one's environment, i.e. adaptive competence. Issues of adaptive competence are especially relevant for children with developmental delay since functional independence is an important long‐term goal for these children. Methods In the present study, mastery motivation was examined in relation to both cognitive and adaptive competence in 5‐year‐old children with Down's syndrome (n = 41). Results Scores on mastery task and parent‐report measures of mastery motivation were generally low, but positively related to scores on standardized measures of cognitive competence and adaptive competence. Conclusions This is the first study of motivation–competence relations in pre‐school‐age children. The findings have implications for both developmental theory and early intervention efforts, and the authors hope that they will serve as a stimulus for future research on cross‐domain relationships in atypical populations.     

Proteins in serum and cerebrospinal fluid in demented patients with Down's syndrome

ABSTRACT— Serum and cerebrospinal fluid (CSF) of 19 Down's syndrome (DS) patients over 35 years old, were examined because of progressive dementia. Immunoglobulins, haptoglobin, transferrin, prealbumin and albumin were quantitated nephelometrically. The results were compared to those obtained for age-matched controls without neurological disease. The concentration of IgG was elevated in the DS serum and CSF, while that of IgA was elevated only in the serum. The level of transferrin was decreased in the DS serum and CSF, and that of albumin in the serum. IgM, haptoglobin and prealbumin concentrations were normal in the DS serum and CSF. No evidence of transudation of proteins into CSF and of their increased intrathecal synthesis was noted. These changes appear not to be associated with the development of dementia in DS.     

Determinants of aggression, and adaptive and maladaptive behaviour in older people with Down's syndrome with and without dementia

In a cross-sectional study of aggression, and adaptive and maladaptive behaviour in 128 subjects with Down's syndrome (DS), 29 of whom had dementia, the current authors found that the presence of dementia was not predictive of aggression or maladaptive behaviour. However, the level of adaptive behaviour was shown to be lower in subjects with dementia, and in those with lower levels of cognitive functioning, as measured on a rating instrument, the Test for Severe Impairment. Although the presence of aggressive behaviours is not higher in subjects with dementia and DS on cross-sectional review, it remains to be seen whether aggression will increase in individual cases with the onset or progression of dementia. The decline in adaptive behaviour shown in the present study confirms the findings of previous studies and indicates a direction for service development for persons with the dual diagnosis of dementia and DS.     

Preliminary evaluation of a scale to assess cognitive function in adults with Down's syndrome: the Prudhoe Cognitive Function Test

Background In the clinical diagnosis of dementia in Down's syndrome (DS), it may be difficult to distinguish between cognitive deterioration and the various degrees of pre‐existing intellectual disability (ID). Serial measurements of both cognitive function and behaviour are required. The aim of the present study was to evaluate the performance of non‐demented adults with DS on a subject‐directed instrument, the Prudhoe Cognitive Function Test (PCFT), preliminary to its serial use in a prospective study. Methods From 1985 to 1986, 85 non‐demented hospitalized adults with DS were interviewed using the PCFT. The Adaptive Behavior Scale (ABS) was administered to the carers. The subjects’ levels of ID (graded from mild through moderate, severe and profound to untestable) were based on their scores on the Stanford–Binet Intelligence Scale, as reported in the medical records, and the relationship between level of disability and performance on the PCFT and ABS, and their respective domains, was examined. Results Both scales produced a wide range of scores and the correlation between them was highly significant. Both scales correlated highly significantly with the degree of ID, but more subjects with high levels (i.e. profound to untestable) of disability obtained very low or zero scores on the PCFT and its domains than on the ABS. Conclusions The PCFT provides a reliable quantitative measure of cognitive function in subjects with DS, and could be a useful adjunct to the diagnosis of dementia in prospective studies. However, the almost uniformly low scores obtained by those with high levels of ID suggests that its power to detect cognitive decline will be limited to those who are less disabled, while the ABS may be more useful than the PCFT in detecting deterioration in people with profound ID.     

Fifteen-year follow-up of thyroid status in adults with Down syndrome

Background The natural history of thyroid function in adults with Down syndrome is relatively unknown with limited long‐term follow‐up data. Method This study investigated annual thyroid function tests in 200 adults with Down syndrome over a 15‐year period. Results For healthy adults with Down syndrome there is a gradual increase in thyroxine and possible gradual decline in thyroid‐stimulating hormone with age. The 15‐year incidence for definite hypothyroidism remains low and subclinical hypothyroidism is not a precursor for the onset of definite hypothyroidism. Conclusions The incidence of thyroid dysfunction is markedly less than would be expected from prevalence studies. Subclinical hypothyroidism is not necessarily a precursor to definite hypothyroidism. Prevalence studies have overstated the association between thyroid dysfunction and Down syndrome. Routine screening for adults with Down syndrome who are euthyroid can be reduced to every 5 years rather than the 1–2 years, as is the present policy.     

Communication profiles of individuals with Down's syndrome, Angelman syndrome and pervasive developmental disorder

The communication profiles of individuals with Down's syndrome (DS), Angelman syndrome (AS) and pervasive developmental disorder (PDD) were investigated and contrasted. Seventy‐seven individuals participated in the study. A within‐group analysis revealed that those with DS performed better on tacting or labelling and echoing than on manding or requesting. No other effects were found, apart from an absence of echoing in those with AS, a result that is hardly surprising. A between‐groups analysis revealed no differences between the aetiological groups in terms of their use of mands or requests and tacts. Individuals with DS and PDD did not differ in their scores on echoic functioning. The implications of these findings for the study of behavioural phenotypes and for communication intervention are discussed.     

Down's syndrome and its association with Alzheimer's disease

The purpose of this study was to ascertain the frequency of Alzheimer's dementia in the relatives of Down's probands and to establish whether these two disorders cluster together. Out of 128 families of Down's probands, only 67 responded to the questionnaire. Twelve cases of Alzheimer's dementia were found in the eight families of 67 probands. There was a significant increase in the frequency of presenile dementia, but no significant increase in senile dementia among the first and second degree relatives of these probands. The methodological problems were discussed and future directions suggested.