Understanding adult outcomes via infancy studies: Neuro-cognitive phenotypes of... with Down syndrome may predict protective/risk markers for Alzheimer’s disease

Understanding adult outcomes via infancy studies: Neuro-cognitive phenotypes of infants
with Down syndrome may predict protective/risk markers for Alzheimer’s disease
Esha Massand & Annette Karmiloff-Smith
Birkbeck Centre for Brain & Cognitive Development, University of London and LondDownS Consortium
• 36-50% of individuals with DS: AD brain pathology
by age 30
• Amyloid precursor protein (APP) gene on Hsa21 overexpressed from infancy onwards
• Signs of amyloid plaque build-up already present in
some infants
• Still not understood why some do/don’t develop
AD clinical phenotype
Measures (contd.)
High-density electroencephalography
• Event Related Potentials (ERPs)
• Resting State EEG
• Very easy to administer to babies
• Individual differences in temporal patterns of brain activity
Motion Capture
• Assess balance/ posture/
gait/gross/fine motor skills
Often similar scores
• Baseline/Spontaneous EEG
• Trace phenotypic outcome back to origins in early
• Elucidate individual differences in DS infants associated
with specific neurocognitive phenotypes of AD
• Focus on outliers as a meaningful source of variation
• Discover protective vsrisk markers for AD
• 150 infants between 6 & 40 months
• high/low-functioning subgroups followed
different neural processes
• Prefrontal lobes
• APP Expression differs across 24 hours sleep/wake
• Changes in sleep precede AD symptoms in TD adults
• Speech/Pitch discrimination task.
• Individual sleep differences in DS infants:
protective vs risk?
Mismatch negativity (MMN) and P3a
(attention to auditory stimuli).
• Sleep patterns in DS= different from other
neurodevelopmental disorders.
• Detect pertinent individual differences in infancy
• Target early intervention for those likely to develop AD
• Link our findings with other LonDownS studies:
mouse models, genetic and cellular profiles of those
with/without AD clinical symptoms
• Non-verbal infant tasks correlated with parental
• questionnaires, cognitive and socio-economic profiles
• Detailed Demographic Questionnaire
• Communicative Developmental Inventory
• Vineland Adaptive Behaviour Scales
• Infant Behavioural Questionnaire
• Infant Sleep Questionnaire
• Sleep diary
Face Pop-Out Task
Emotion /Gaze Task
View faces with emotion, gaze averted/
direct. Limbic system. 1st Look measured
• Recognition Memory
Temporal/ Hippocampal
Paired Associate Learning
Infant with DS Infant with
Individual Differences
cascading effects on developing
cognitive domains and behaviour.
Gap-overlap task
DS infants
McGurk Effect
Visual/Auditory mismatch
Karmiloff-Smith, A. et al.(2012). Genetic and environmental vulnerabilities in children with neurodevelopmental disorders. Proc. Natl. Acad. Sci. USA, 109, 17261-17265.
Deferred Imitation
Free Recall with Delay