Obesity, diabetes and their metabolic correlates in middle-aged adults with Down syndrome.

BACKGROUND: Obesity in adults without Down syndrome is associated with an adverse metabolic profile including high prevalence of pre-diabetes and diabetes, high levels of insulin, non-high-density lipoprotein (HDL) cholesterol, leptin and high-sensitivity C-reactive protein (hsCRP) and low levels of HDL and adiponectin. We examined whether obesity in middle-aged adults with Down syndrome is also related to an adverse metabolic profile. METHODS: This cross-sectional study included 143 adults with Down syndrome, with a mean age of 55.7 ± 5.7 years and 52.5% women. Body mass index (BMI) was classified as underweight (BMI < 18.5 kg/m2 ), normal (BMI 18.5-24.9 kg/m2 ), overweight (BMI 25-29.9 kg/m2 ) and obese (BMI ≥ 30 kg/m2 ). Diabetes was ascertained by history or by haemoglobin A1c (HbA1c) as normal glucose tolerance (HbA1c < 5.7%), pre-diabetes (HbA1c 5.7-6.4%) and diabetes (HbA1c ≥ 6.5%). We measured non-fasting lipids, hsCRP, insulin, adiponectin and leptin. RESULTS: The majority of the sample had an overweight (46.9%) or obesity (27.3%) status. However, there was a relatively low prevalence of pre-diabetes (9.8%) and diabetes (6.9%). Overweight and obesity status were not associated with lower HDL and adiponectin and higher insulin, non-HDL cholesterol and hsCRP as expected in adults without Down syndrome. However, overweight and obesity were strongly associated with higher leptin (P < 0.001). CONCLUSIONS: The only metabolic correlate of obesity in middle-aged adults with Down syndrome was high leptin levels. Our findings are limited by non-fasting laboratory tests but suggest that middle-aged adults with Down syndrome do not have the adverse metabolic profile related to obesity found in adults without Down syndrome.

An improved method for detecting telomere size differences in T-lymphocyte interphases from older people with Down syndrome with and without mild cognitive impairment.

Telomere size (quantified by fluorescence intensity and physical lengths) in short-term T-lymphocyte cultures from adults with Down syndrome (DS) with and without mild cognitive impairment (MCI-DS) or dementia was compared. For these studies, dementia status was determined based on longitudinal assessments employing a battery of cognitive and functional assessments developed to distinguish adult-onset impairment from preexisting developmental disability. In the course of our studies using a MetaSystems Image Analyzer in combination with ISIS software and a Zeiss Axioskop 2, we found that Fluorescein isothiocyanate (FITC) telomere fluorescence referenced to chromosome 2-identified FITC probe fluorescence as a nontelomere standard (telomere/cen2 ratio) showed great promise as a biomarker of early decline associated with Alzheimer's disease (AD) in this high-risk population. We have now obtained a cen (2) CY3 probe that can clearly be distinguished from the blue-green FITC interphase telomere probe, providing a clear distinction between telomere and centromere fluorescence in both interphase and metaphase. We used FITC/CY3 light intensity ratios to compare telomere length in interphases in adults with DS with and without MCI-DS or dementia. Five age-matched female and five age-matched male pairs (n = 10) all showed clear evidence of telomere shortening associated with clinical progression of AD (P < 0.002 - P < 0.000001), with distributions of mean values for cases and controls showing no overlap. We also examined the time needed for microscopy using interphase versus metaphase fluorescence preparations. With interphase preparations, examination time was reduced by an order of magnitude compared with metaphase preparations, indicating that the methods employed herein have considerable practical promise for translation into broad diagnostic practice.

Verbal intrusions precede memory decline in adults with Down syndrome.

BACKGROUND: Verbal intrusion errors are irrelevant responses made in the course of verbal memory retrieval or language production that have been associated with disruption of executive functions and the prefrontal cortex. They have been observed to occur more frequently both with normal aging and with neurodegenerative diseases such as Alzheimer's disease (AD). The purpose of this study was to longitudinally examine the production of verbal intrusions among middle-aged adults with Down syndrome (DS) and unspecified intellectual disability (ID) to determine whether producing verbal intrusions at one point in time was related to subsequent verbal memory performance. Because of the combination of a relative deficit in verbal working memory (WM), premature aging, and higher risk of AD among adults with DS, it was predicted that they would make more verbal intrusions than adults with unspecified ID. METHODS: Word List recall (WLR), the Selective Reminding Test (SRT), and the Cued Recall Test (CRT), were administered three times at 18-month intervals during a 3-year period. In Analysis 1, aetiology differences in making intrusion errors were examined. Twenty-three adults with unspecified ID in the moderate to mild range [time 1(T1) mean age = 47.2 years] and 42 adults with DS (T1 mean age = 44.3) participated. WLR is a serial WM task beginning at two word sequences and progressively increasing by one word every three trials. WLR intrusions were analysed because they were least likely to include 'educated guesses' because this test is not based on semantic categories. In Analysis 2, we only examined participants with DS. They were divided into two groups, 16 individuals who made at least one intrusion error at T1 (T1 mean age = 45.8) and 26 who did not (T1 mean age = 43.3). Longitudinal performance for these groups was analysed to determine whether the group that intruded at T1 did more poorly on subsequent memory tests. RESULTS: A higher proportion of responses comprised intrusions for the group with DS and a higher percentage of the participants with DS made at least one intrusion error when compared with participants with unspecified ID (74% and 44% respectively). Those participants with DS who made at least one intrusion error at T1 showed a subsequent decline in performance on both WLR and the SRT. CONCLUSIONS: The production of intrusion errors during a verbal WM task is a characteristic of middle-aged adults with DS. This suggests compromised executive function and control of inhibition within the verbal modality for this group. Further, verbal intrusions are a qualitative aspect of verbal processing that merit attention in considering the issue of deficiencies of language and verbal WM abilities among people with DS. Last, and perhaps most importantly, although not definitive diagnostically, an increase in verbal intrusions is a potentially noteworthy signal when evaluating the cognitive health of adults with DS.

Dementia of the Alzheimer's type and accelerated aging in Down syndrome.

This case study, of a woman with Down syndrome and dementia of the Alzheimer's type (DAT), follows the course of her decline over an 11-year period until death at age 57. Detailed neuropathological findings are also presented. This case illustrates features of premature aging that are typically associated with Down syndrome, and the progressive changes in memory and cognition that are usually associated with DAT. Although the subject's cardiovascular condition and thyroid disorder were treated, they may have contributed to the decline of her memory. This case shows the difficulty in diagnosing dementia in an individual with mental retardation who suffered comorbid episodes of depression and psychosis.

Sex differences in performance over 7 years on the Wechsler Intelligence Scale for Children--Revised among adults with intellectual disability.

BACKGROUND: The aim of this study was to explore changes related to sex differences on the Wechsler Intelligence Scale for Children - Revised (WISC-R) subtest performance over a 7-year interval in middle-aged adults with intellectual disability (ID). Cognitive sex differences have been extensively studied in the general population, but there are few reports concerning individuals with ID. Sex differences are of current relevance to actively debated issues such as cognitive changes during menopause and risk for Alzheimer's disease. Given that hormonal effects on cognition have been observed in the general population, particularly in areas such as visuospatial processing, and individuals with Down's syndrome (DS) have been reported to be hormonally and reproductively atypical, we analysed our data to allow for the possibility of an aetiology-specific profile of sex differences for these adults. METHODS: The WISC-R subtests were administered in a longitudinal study, as part of a more comprehensive test battery, at least twice within 7 years. Participants were 18 females with ID without DS [age at first test time (time 1): mean = 40.5; IQ: mean = 59.3], 10 males with ID without DS (age at time 1: mean = 42.4; IQ: mean = 59.4), 21 females with DS (age at time 1: mean = 37.9; IQ: mean = 51.6), and 21 males with DS (age at time 1: mean = 40.3; IQ: mean = 54.3). All participants were in the mild to moderate range of ID and were displaying no changes suggestive of early dementia. RESULTS: Females, regardless of aetiology of ID, exhibited a robust superiority on the coding subtest, which parallels the widely reported difference among adults in the general population. Additionally, there was a decline in overall performance during the 7-year study interval, particularly on the verbal subscale subtests, but there was no evidence of sex-differentiated decline. There were also marginal sex by aetiology interactions on the object assembly and block design subtests, suggesting that males with unspecified ID might perform better than their female peers, but among adults with DS, females might do better than males. CONCLUSIONS: This study supports the presence of cognitive sex differences in the population with ID as indicated by female superiority on the WISC-R coding subtest. Extending this observation to adults with ID has implications for explanations of female advantage on this task, which now have to account for its presence among individuals with a broader range of intellectual capabilities, more atypical developmental histories and more varied genotypes than previously considered. Trends towards sex by aetiology interactions on the two visuoconstructive subtests, while marginal, were sufficient to warrant continued consideration of the idea of a distinct profile of sex differences for adults with DS and to justify looking at the effects of sex separately within different aetiologies of ID.

Cued recall in early-stage dementia in adults with Down's syndrome.

BACKGROUND: Memory declines were evaluated with an adaptation of the Cued Recall Test (CRT) in 19 adults with Down's syndrome (DS) with mild or moderate intellectual disability (ID) who were at an early-stage of dementia of the Alzheimer type (DAT), and their performance was compared to peer groups of 75 adults with DS and 66 adults with ID without DS who were not suspected of functional declines. METHOD: The CRT consisted of a training period in which 12 items were presented, four at a time, with each item accompanied by a unique category cue. The testing phase consisted of three trials which generated two measures, a free recall score (FRS; spontaneous recall of the list of 12 items) and a total score (TS; FRS plus items recalled when the category cue was provided). RESULTS: It was found that a cut-off value of < or = 23 on the TS resulted in a sensitivity of 94.7% and a specificity of 93.9% with a positive predictive value of 81.9% when those individuals with DAT were compared to the participants with ID without DS. Eight of these individuals with DAT had relatively poor performance on the CRT compared to their healthy peers at a baseline when they were not suspected of functional declines, suggesting that memory declines can occur several years prior to the identification of DAT. In addition, 17 participants with DS without a diagnosis of DAT met the criterion for the cut-off score. Longitudinal data and converging measures indicated that there was the possibility that 15 of these individuals are in a 'pre-clinical' stage of decline. CONCLUSION: The usefulness of the CRT as a screening test for early memory deficits for this population needs to be confirmed by following these participants for an extended period of time and by studying an independent sample.

Changes in explicit memory associated with early dementia in adults with Down's syndrome.

BACKGROUND: A modified version of the Selective Reminding Test (SRT) (Buschke 1973) was used to examine the changes in memory that occur with early-stage dementia of the Alzheimer's type (DAT) in adults with intellectual disability (ID) and Down's syndrome (DS), and to compare these changes to those occurring with 'normal' ageing. METHOD: Hierarchical linear modelling analyses showed steep declines in the performance of participants who had met the criteria for the onset of DAT. Non-demented participants also showed declines in performance which were related to their age. However, the absolute magnitude of these declines was consistent with a 'normal' ageing pattern and not with undetected dementia. RESULTS: In analysing the specific memory components that are compromised, the present authors found that participants with early-stage DAT showed severely diminished long-term storage and retrieval processing abilities compared to their non-demented peers. Notably, these declines preceded other symptoms of dementia, in most cases by more than a full year and sometimes by as much as 3 years. CONCLUSIONS: Thus, the present results clearly confirm that memory processes are affected during early dementia in adults with DS, and that the SRT has promise as a clinical tool.

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.