Investigating cognition and Alzheimer’s Disease in adults with Down’s Syndrome
1,2
Startin ,
1
Sinai ,
1
Mokrysz
1,2
Strydom
Carla
Amanda
Claire
and Andre
1 Mental Health Sciences Unit, University College London, London UK
2 LonDownS Consortium, London UK
Introduction
•
•
Methods 2
LonDownS
• Cohort 1: adults with DS aged 40 and over
(n = 200). Followed longitudinally over 3 years
(3 assessments, 18 months apart)
• Measure baseline electroencephalography (EEG)
activity to investigate cortical connectivity
• This study will form a part of the work by the
LonDownS consortium. This consortium aims to link
differences in individual cognitive and clinical profiles
of those with DS to differences in terms of their
genetic, molecular and cellular profiles. In particular,
we will look at phenotypes related to AD
Methods 1
• Individuals with Down’s Syndrome (DS) show large
variability in terms of their cognitive profiles,
including abilities relating to executive function,
memory, language and motor co-ordination, and to
the clinical presentation of Alzheimer’s Disease (AD)
• The increased risk of AD in individuals with DS is
thought to be due to over-expression of genes on
chromosome 21 due to their triplication
• The amyloid precursor protein (APP) gene is one of
the likely candidates, as it contributes to the build-up
of amyloid plaques in the brains of individuals with
AD and is associated with early onset AD
• Although all individuals with DS show these
amyloid plaques in their brains at the age of 30, only
around a third of those with DS aged 30 and over
show the clinical signs of AD
• Data from our group suggests that the age of onset
of AD in individuals with DS shows a large variability;
while the median age of onset is 55.45 years (IQR
50.98-59.39 years), the age of onset ranges from
32.83 to 85.11 years
Age of
diagnosis of
AD for
individuals
with DS from
the ADSID
(Ageing with
Down
Syndrome or
Intellectual
Disability)
database
(n = 339,
participants
from South
England)
• We will investigate individual differences in those
with DS in terms of their cognitive profiles, and in
particular in terms of the presentation of AD
• Cohort 2: individuals with DS aged 16-30 (n = 150).
Assessed once initially, selected individuals will be
followed longitudinally
• Use a variety of tasks to characterise abilities
associated with frontal, hippocampal, temporal and
cerebellar regions (executive function, memory,
language and motor co-ordination respectively), as
well as assessing general cognitive abilities using
the K-BIT II
• Measure sleep patterns using actigraphy and by
asking participants / carers to
keep a sleep diary (disrupted
sleep may precede the onset of
AD)
Executive function
• Intra-extra dimensional
set shift (CANTAB)
• Modified dots (ACTB)
• Tower of London
• Collect informant ratings to assess the individual’s
everyday functioning (the Vineland Adaptive
Behaviour Scale, the Scales of Independent
Behaviour (SIB), the Behaviour Rating Inventory of
Executive Function (BRIEF), the mini Psychiatric
Assessment Schedules for Adults with
Developmental Disabilities (mini PAS-ADD), and the
Dementia Questionnaire for People with Learning
Disabilities (DLD))
Memory
• Paired associate learning
(CANTAB)
• Memory for objects /
sentences (NAID)
Language
• Verbal fluency (NEPSY)
Motor co-ordination
• Simple response time
(CANTAB)
• Finger sequencing task
(ACTB)
• Finger-nose pointing
• Visuomotor precision (NEPSY)
ACTB: Edgin JO, Mason GM, Allman MJ, Capone GT, Deleon I, Maslen C, Reeves
RH, Sherman SL and Nadel L (2010). J Neurodev Disord 2: 149-164
CANTAB: Robbins TW, James M, Owen AM, Sahakian BJ, McInnes L and Rabbitt P
(1994). Dementia 5: 266-281
NAID: Crayton L, Oliver C, Holland A, Bradbury J and Hall S (1998). J Appl Res
Intellect Disabil 11: 255-272
• We will investigate these differences in adults with
DS and the developmental origins of these
differences in infants with DS, using comparable
assessments across the different age groups
• We will use mouse models of DS and AD to
investigate the effects of specific genes on APPdriven AD-like changes
• We will hopefully identify risk and protective factors
for the development of AD in individuals with DS. In
the future this will lead to improved diagnosis,
treatment and care for those with DS
• Collect demographic information and a detailed
medical history for all participants, as well as
assessing physical health and vision / hearing
• Obtain either a blood or saliva sample for genetic
analysis, and take a hair sample for the generation
of induced pluripotent stem cells to produce neurons
BRIEF: Gioia GA, Isquith PK, Guy SC and Kenworthy L (2000). Child Neuropsychol
6: 235-238
DLD: Prasher VP (1997). J Appl Res Intellect Disabil 10: 54-60
PAS-ADD: Taylor JL, Hatton C, Dixon L and Douglas C (2004). J Intellect Disabil Res
48: 37-41
SIB: Bruininks RK, Woodcock RW, Weatherman RF and Hill BK (1997)
Vineland: Sparrow SS, Cicchetti DV and Balla DA (2007)
Andre Strydom
John Hardy
Elizabeth Fisher
Annette Karmiloff-Smith
Dean Nizetic
Victor Tybulewicz