Down

syndrome, Seizures and

Demen2a
Ira T. Lo7, MD
Director, Down Syndrome Program
Professor Emeritus
University of California, Irvine

Seizures in DS
Prevalence of seizures 8-27% in DS

Compared to 1-5% general popula2ons

In DS, seizures most common in infancy in
mid-late life

West Syndrome

Infan2le spasms in DS
Median onset 7 months
ONen associated with developmental
regression such as eye tracking, loss of smile,
and decreased responsiveness

Prognosis for infan2le spasms in DS

(Shinnar and colleagues, 2013)
ACTH usually successful
But relapses may occur up to 2 years aNer
treatment
More rare is intractable epilepsy, profound
disability and au2s2c symptoms

 EEG has characteris2c pa7erns as people with

DS age

Accumula2on of amyloid plaques in the

hippocampus associated with seizure
discharges (Noebels, 2011)
May herald onset of demen2a

LOMEDS (Vignoli et al, 2011)

Slow EEG in demen2a

Brain Architecture in DS
(Lo7 and Dierssen, 2012)

Early neuronal dysfunction in DS-a target for

interventions

Seizures hasten cogni2ve decline in

demen2a DS (Doran et al, 2012)
SIB
Variable

BPT

Est. (95% CI)

p-value

Est. (95% CI)

p-value

Age

1.10 (0.96, 1.26)

0.161

1.09 (0.94, 1.26)

0.248

Female

0.49 (0.14, 1.66)

0.252

0.54 (0.16, 1.78)

0.308

APOE: 24, 34 or 44

1.78 (0.46, 6.82)

0.401

0.56 (0.11, 2.73)

0.472

0.36 (0.00, 122.97)

0.729

0.31 (0.00, 177.73)

0.715

DMR Cognitive

1.12 (1.00, 1.24)

0.042

1.06 (0.96, 1.16)

0.267

Interaction: Pre-morbid CI and

DMR

1.08 (0.90, 1.30)

0.431

1.07 (0.88, 1.29)

0.509

11.58 (1.91, 70.32)

0.008

9.21 (2.08, 40.80)

0.003

Pre-morbid Cognitive Impairment:

Severe or Profound

Seizure status

AED compliance in ID (Hom et al,

2013)
Semi-independent vs. group home p< 0.0003
Family home vs. group home p< 0.0000
Semi-independent vs. family home p< 0.3368

Can AED improve cogni2on in

demen2a (Bakker, Yassa et al, 2012)
For pa2ents with mild cogni2ve impairment
(general popula2on)

Keppra improved hippocampal ac2va2on by MRI
and improved hippocampal func2on on specic
tes2ng (p>.02)

A role for middle age adults with DS?

Conclusions
Seizures in adults with DS may herald
demen2a
Amyloid accumula2on appears related to EEG
seizure discharges
AED may improve cogni2on in DS prior to the
onset of clinical seizures and during the
transi2onal phase to demen2a
AED compliance may be a challenge

UCI Down Syndrome Team

Eric Doran, MS-Program Manager
Nina Movsesyan, PhD-Research Coordinator
Anne Tournay, MD-Neurologist
Mindora Totoui,MD, PhD-Neurologist
David Walsh, PhD-Psychologist
Supported in part by HD25912, HD065160, AG16572 ; State
of California