The LonDownS adult cognitive assessment to study cognitive abilities and decline in Down syndrome

Abstract

Background: Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with an ultra-high risk of developing Alzheimer’s disease. However, there is individual variability in the onset of clinical dementia and in baseline cognitive abilities prior to decline, particularly in memory, executive functioning, and motor coordination. The LonDownS Consortium aims to determine risk and protective factors for the development of dementia and factors relating to cognitive abilities in people with DS. Here we describe our cognitive test battery and related informant measures along with reporting data from our baseline cognitive and informant assessments. Methods: We developed a cognitive test battery to assess general abilities, memory, executive function, and motor coordination abilities in adults with DS, with informant ratings of similar domains also collected, designed to allow for data on a broad range of participants. Participants (n=305) had a range of ages and abilities, and included adults with and without a clinical diagnosis of dementia. Results: Results suggest the battery is suitable for the majority of adults with DS, although approximately half the adults with dementia were unable to undertake any cognitive task. Many test outcomes showed a range of scores with low floor and ceiling effects. Non-verbal age-adjusted IQ scores had lower floor effects than verbal IQ scores. Before the onset of any cognitive decline, females aged 16-35 showed better verbal abilities compared to males. We also identified clusters of cognitive test scores within our battery related to visuospatial memory, motor coordination, language abilities, and processing speed / sustained attention. Conclusions: Our further studies will use baseline and longitudinal assessments to explore factors influencing cognitive abilities and cognitive decline related to ageing and onset of dementia in adults with DS.

Aging related cognitive changes associated with Alzheimer's disease in Down syndrome

“…Furthermore, Lautarescu and colleagues highlighted that those with a standardized IQ < 40 had very low scores on the memory tasks used, regardless of their dementia status. The CANTAB PAL and object memory tasks used in our battery (but none of the reviewed studies) allowed us to assess visuospatial memory and immediate and delayed recall of everyday items in the majority of our sample, with fewer than 1% of our younger adults aged [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] (including many with IQ < 40) at floor on delayed object memory trials, 11 suggesting that these specific tests are suitable for those with DS and can identify decline in this population. However, for the object memory task, 40% of our younger adults were scoring at ceiling for the delayed object memory trial, suggesting this test may be insufficiently sensitive for measuring ability changes in those with comparatively strong premorbid delayed object memory.…”

“…Tests were validated in older adults with DS 50 before being applied in a large sample including both younger and older adults with DS which allowed for selection of tests with acceptable floor and ceiling effects. 11 However, we acknowledge the lack of tasks specifically focusing on verbal memory, which is often one of the earliest domains affected in AD.…”

“…In individuals with DS, the development of dementia needs to be understood in the context of a complex cognitive phenotype that not only includes general ID, but also specific impairments in executive function, memory, language, and motor domains. 10,11 Such pre-existing impairments in those with DS need to be distinguished from subsequent decline, and in combination with varying baseline abilities and limitations in speech abilities can make the interpretation of cognitive test data, and thus clinical diagnosis, difficult. 12, 13 The evaluation of longitudinal change suggestive of AD in DS, within and across different cognitive domains, poses significant challenges.…”

Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in-vivo fetal and neonatal MRI assessment

“…Despite the noted groupwise differences in brain development (DS compared to age-matched controls), we found overlap in almost all assessed parameters, highlighting a spectrum of atypical development across the DS cohort. This is of interest but perhaps not unexpected given the recognised individual variability in neurodevelopmental outcome of DS individuals, as established for instance ,by IQ scores 6,[27][28][29] .…”

“Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene-dose-sensitive AD-suppressor in human brain”

“…BACE2 locus SNPs: The cohort of people with DS has been described in recent reports 22,23 . In brief, participants donated DNA samples and had detailed cognitive and clinical assessments to determine dementia status 54 . Age of dementia diagnosis was established and used in SNP analysis.…”