Down Syndrome & Aging Abstracts

Clin Neuropharmacol 26 (5): 277-83 (2003 Sep-Oct)

Progressive worsening of adaptive functions in Down syndrome may be mediated by the complexing of soluble Abeta peptides with the alpha 7 nicotinic acetylcholine receptor: therapeutic implications

Deutsch SI, Rosse RB, Mastropaolo J, Chilton M.
Mental Health Service Line, VISN5, Department of Veterans Affairs Medical Center, 50 Irving Street NW, Washington, DC 20422, USA

In persons with Down syndrome, soluble Abeta peptides, which result from the processing of the amyloid precursor protein, appear in the brain decades before the extracellular deposition of neuritic plaques. These soluble amyloidogenic peptides accumulate intraneuronally and can be secreted extracellularly. Their appearance has been reported in the brains of fetuses with Down syndrome. The extra gene dosage effect associated with trisomy 21 results in abnormalities of the processing of amyloid precursor protein in persons with Down syndrome. Abeta peptides, especially Abeta1-42, have been shown to form tight complexes with the alpha7 nicotinic acetylcholine receptor, interfering with transduction of the acetylcholine signal by this nicotinic receptor subtype. Furthermore, the selective binding of Abeta peptides by this nicotinic acetylcholine receptor subtype is associated with cytotoxicity. The alpha7 nicotinic acetylcholine receptor has unique electrophysiologic properties and plays a prominent role in normal psychophysiologic processes (eg, sensory inhibition) and cognition. In persons with Down syndrome there is a decrease in the ability to perform instrumental activities of daily living that worsen with aging. The progressive worsening of adaptive functions and cognition in persons with Down syndrome may be, at least in part, mediated by interference with this receptor by soluble Abeta peptides. In view of this complex formed by soluble Abeta peptides and the alpha7 nicotinic acetylcholine receptor, cholinergic interventions that have been developed for Alzheimer disease, including selective nicotinic ones, should be explored in Down syndrome. Ideally, selective cholinergic interventions would slow the progression of the worsening of adaptive function and emergence of dementia in persons with Down syndrome.
Mech Ageing Dev 106 (1-2): 155-60 (1998 Dec 1)

Serum hyaluronic acid in Down's syndrome

Hutchin T, Martin L, Prasher V, Sinclair AJ
Academic Department of Geriatric Medicine and Gerontology, University of Birmingham, Selly Oak Hospital, UK

In agreement with previous studies we show an age-related increase in serum levels of hyaluronic acid in healthy individuals. Levels in Down's syndrome persons were slightly higher, especially in those with hypothyroidism. This provides further evidence that the normal ageing process is accelerated in Down's syndrome.
J Geriatr Psychiatry Neurol 10 (3): 99-104 (1997 Jul)

Treatment of functional decline in adults with Down syndrome using selective serotonin-reuptake inhibitor drugs

Geldmacher DS, Lerner AJ, Voci JM, Noelker EA, Somple LC, Whitehouse PJ
Alzheimer Center, University Hospitals of Cleveland, USA

Alzheimer's disease (AD) is a common cause of functional decline in Down syndrome (DS) adults. Acquired cognitive deficits may be difficult to evaluate in the context of baseline impairments. Behavioral symptoms are also common and may represent the effects of depression, AD, or both. Therefore, the objective of this study was to report a clinical case series of selected adults with DS and behavioral change who responded to treatment with selective serotonin-reuptake inhibitor (SSRI) medication. Six patients, aged 23 to 63 years, 5 women and 1 man, with the clinical diagnosis of DS presented for diagnosis and treatment of functional decline in adult life. Noncognitive symptoms were prominent and included aggression, social withdrawal, and compulsive behaviors. Memory dysfunction was reported in varying degrees. Treatment with SSRI antidepressants was instituted for depressive, apathetic, and compulsive behaviors. Treated patients showed improvement in behaviors as reported by caregivers, and on objective measures, such as workplace productivity. Noncognitive symptoms are a cardinal feature of functional decline in adults with DS and may represent either depression or AD. In some patients, the symptoms respond well to SSRI agents with concomitant improvement in daily function. Treatment trials with SSRIs may, therefore, be warranted in such cases.
J Intellect Disabil Res 40 (3): 208-21 (1996 Jun)

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

Devenny DA; Silverman WP; Hill AL; Jenkins E; Sersen EA; Wisniewski KE
New York State University for Basic Research in Developmental Disabilities, USA

The ubiquitous presence of the neuropathology 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 neuropathology 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 (31-76 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 50 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 functioning 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 functioning are related to "normal" but probably precocious Aging 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.
Am J Neuroradiol 17 (7): 1283-1289 (1996)

Premature aging in persons with Down syndrome: MR findings

Roth GM, Sun B, Greensite FS, Lott IT, Dietrich RB
Department of Radiological Sciences, University of California, Irvine Medical Center, Orange 92668, USA

PURPOSE: To determine whether persons with Down syndrome have features of premature aging on routine MR imaging sequences. METHODS: Sixty MR studies (in 30 persons with Down syndrome and 30 age- and sex-matched control subjects) were reviewed retrospectively by two blinded examiners. Sagittal T1-weighted and axial T2-weighted spin-echo images were evaluated for the presence and severity of three markers of brain aging: atrophy, white matter lesions, and T2 hypointensity of the basal ganglia, referenced to the examiner's internal standard of normal for that age and sex. RESULTS: Persons with Down syndrome had higher prevalence and severity of the three markers studied than the control subjects. Atrophy and white matter lesions increased in prevalence with age; abnormal T2 hypointensity of the basal ganglia was more equally distributed with age. CONCLUSION: Persons with Down syndrome have features of premature aging detectable at routine MR imaging.
Res Dev Disabil 16 (6): 461-78 (1995 Nov-Dec)

Cognitive decline due to aging among persons with Down syndrome

Das JP, Divis B, Alexander J, Parrila RK, Naglieri JA
Developmental Disabilities Centre, University of Alberta, Edmonton, Canada

This study examined decline in cognitive functions in individuals with Down syndrome (DS) over the age of 40 in comparison to participants of the same age and comparable mental handicap without Down syndrome (NonDS). Both DS (n = 32) and NonDS (n = 31) samples were divided into "younger" (40-49 years) and "older" (50-62) groups. Cognitive processes were examined by tests of general intellectual functioning (Dementia Rating Scale, Peabody Picture Vocabulary Test-Revised, and the Matrix Analogies Test-Expanded form), as well as planning, attention, simultaneous, and successive processing tests taken from Das-Naglieri Cognitive Assessment System. The older individuals with Down syndrome performed more poorly than those in the other three groups. The differences were particularly evident in tasks requiring planning and attention. The possibility of using these tests as indicators of the early signs of Alzheimer's disease is discussed.
J Intellect Disabil Res 36 (3): 241-50 (1992 Jun)

Ageing in Higher Functioning Adults with Down's Syndrome: An Interim Report in a Longitudinal Study

Devenny DA; Hill AL; Patxot O; Silverman WP; Wisniewski KE
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314

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 and 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 of 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.
Am J Ment Defic 92 (2): 161-168 (1987 Sep)

Premature regression of adults with Down syndrome

Zigman WB, Schupf N, Lubin RA, Silverman WP

Adaptive skills of 2,144 individuals with Down syndrome were compared to a similar group of 4,172 developmentally disabled people without Down syndrome. Activities of daily living and cognitive skills were examined across etiology, age group, and level of mental retardation. For individuals with Down syndrome at all levels of retardation, adaptive competence declined with increasing age to a greater extent than for retarded control subjects. Clear age-related deficits associated with Down syndrome were observed only in people older than 50 years of age. Findings support previous evidence of an increased risk for the clinical signs of Alzheimer's disease among people with Down syndrome; however, signs of dementia appeared later in life than would be predicted from available neuropathological data.