Cognitive Impairments in HD
Sarah Farias, Ph.D.
Clinical and Research Neuropsychologist
Associate Professor, Dept. of Neurology
University of California, Davis
5/29/2013
Cognitive Impairments in HD
Outline
 A little brain anatomy and brain changes
in HD
 Cognitive impairments that can occur in
HD
 Approaches to managing these cognitive
changes
Cognitive Impairments in HD
Background
 Cognitive changes are among the most debilitating
aspects of HD
 Very subtle changes can start early in HD
 They eventually lead to reduced job performance
and contribute to loss of functional abilities (e.g.
driving, cooking safely)
 The cognitive and secondary functional
consequences can also create stress for families of
affected individuals
 Knowledge is power: knowing what to expect can
lead to better compensation
Cognitive Impairments in HD
Brain Anatomy and Function
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 Motor Abilities
 Executive functions:
Planning
Prioritizing
Multi-tasking
Monitoring behavior
 Social/emotional
behavior
Spatial Abilities
Math
Reading
Somatosensory
 Vision
 Interpreting
visual input
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Hearing
Language
Memory
Emotions
Cognitive Impairments in HD
Brain Circuitry
 Different brain regions need
to communicate to work
together
 The brain is organized as
interrelated circuits or
pathways that connect
different parts of the brain
 Because they function
together as a circuit,
disruption anywhere along
the path causes dysfunction
of the entire circuit
The light bulb cannot give off light
if the circuit is disrupted anywhere
along the path
Cognitive Impairments in HD
Brain Changes in HD:
Cell Death in the Caudate Nucleus
Normal
Advanced HD
Cognitive Impairments in HD
Caudate Nucleus:
An Important Relay Station
Key Functions of the
Caudate:
1. Connects different regions
of the brain
2. Regulates the flow of
information
3. Has the most connections
with the frontal lobes
Cognitive Impairments in HD
Functions of the Frontal lobe
MOTOR
COGNITIVE*
EMOTIONAL
Cognitive Impairments in HD
Thinking Abilities Related to the Frontal Lobes:
Executive Functions
The ‘CEO’ of the Brain
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Planning and organization
Decision making
Reasoning and judgment
Problem solving
Anticipating consequences
Knowing when to initiate a behavior and when it is no
longer needed
 Divided Attention
 Creative thinking
 Regulation of other basic abilities such as attention,
perception, language, and memory
Cognitive Impairments in HD
Impairments in Executive Functions
 Disorganization
 Problems keeping up with finances and other paperwork
(loosing important documents)
 Problems keeping track of one’s schedule (e.g. missing
appointments)
 Difficulty prioritizing and sequencing tasks
 Tasks like following a recipe, developing a meeting agenda or
applying for social security become overwhelming
 Poor judgment
 Not weighing the consequences
 Making bad decisions at work, poor financial decisions
Cognitive Impairments in HD
Impairments in Executive Functions
(cont.)
 Problems with ‘mental flexibility’
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Only seeing something ‘one way’
Getting stuck on certain ideas
No longer able to multi-task/do more than one thing at a time
Easily distracted by other things in the environment
Becoming overwhelmed by new or chaotic circumstances
 Processing speed reductions
 It takes longer to do tasks
 Tasks are more mentally draining then they used to be
 Problems tracking time
 Difficulty estimating how long a task will take
 Difficulty judging how much time has elapsed
Cognitive Impairments in HD
Impairments in Executive Functions
(cont.)
 Reduced impulse control
 Saying things without thinking first
 Difficulty regulating eating, smoking, sexual behavior
 Shop lifting
 Problems with apathy
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Difficulty “getting started”
Difficulty following through with tasks
Watching TV for long periods of time
Not keeping up with hygiene
Does not = laziness
Cognitive Impairments in HD
Compensatory Strategies
 Use ‘external aids’ to assist the CEO!
 Use a daily ‘To Do’ list (helps with ‘getting going’ and
what order to tackle things)
 Break big jobs into little steps
 Use a calendar (place in highly visible location)
 Use alarms and reminders on smart phones
 Keep a routine schedule
 Recruit an Executive Assistant - all CEOs have one!
 Allow for extra time
 Keep trips short, go to familiar places
Cognitive Impairments in HD
Compensatory Strategies
(cont.)
 Minimize distractions
 Do only one thing at a time – limit radio and/or
talking while driving, limit conversations and other
distractions while cooking
 Work in a quiet location
 One question at a time! (Minimize stimulus
overload!)
 Prepare for changes in routine
 When repetitive thoughts arise, use distraction,
go do something, get out of the house
 Use humor – we all make mistakes!
Cognitive Impairments in HD
Cognitive problems in other areas:
Communication
 Communication difficulties:
 Increased slowness in responding during conversation
due to difficulty organizing thoughts
 Word finding difficulty
 Difficulty tracking conversations
 Going ‘off topic’ in conversations
 Reduced spontaneous initiation of conversation
 Strategies:
 Accept that extra time in needed
 Others may need to provide topics of conversation
 Use multiple choice questions rather than open ended
questions
Cognitive Impairments in HD
Cognitive problems in other areas:
Memory
 Memory difficulties:
 Organizational problems and distraction can lead to
problems learning new information
 Difficulties retrieving information from ‘memory stores’
 Motor memory system impairments (later in disease) –
e.g. motor memories associated with driving, playing a
musical instrument, riding a bike
 Strategies to compensate:
 Use hints to help with recall
 When learning information, learn a little at a time
 Use external aids like note books, keep information in
smart phone
 Use calendars
Cognitive Impairments in HD
Additional Things To Consider
 Every person is individual and will have unique
strengths and weaknesses (before and during
the disease)
 Approaches to managing a cognitive issue at
one stage in the disease may need a new ‘fix’
in the next stage
 Even when cognitive impairments result in
limitations in everyday functions, identify ways
to continue family roles and interests
CAM for HD
What is the “Politically Dominant”
Health Care System?
Reflects broad acceptance as evidenced by
“medical practice laws, legally recognized
accreditation…., third party payment,
privileged access to research moneys and
to prestigious publication venues, high
status, and so forth.”
Source: Panel on definition and description, CAM research
methodology conference, Alternative Therapy 1997;3:49-57.
CAM for HD
Integrative Medicine
Combined conventional and CAM treatment approach
CAM for HD
Why Consider CAM for HD?
 Despite the discovery of the gene
responsible for HD in 1993, we don’t yet
have a cure
 Treatments for HD have lagged behind
those of other neurological conditions;
focus on the cure
 Influence of predictive testing: what can a
person who tests positive do while they’re
still healthy?
CAM for HD
HD Treatment Triad*
Spirituality
HD Treatment
Exercise
Diet and
Supplements
*Adapted from Jerry Lampson, www.hdlighthouse.org
CAM for HD
Spirituality
 Multiple paths……organized religion,
massage, relaxation, yoga, meditation
 No research has been published in this
area, but PHAROS and PREDICT studies
are collecting data via questionnaires
from participants
CAM for HD
Exercise
 HD study mice had
delayed onset of HD
symptoms when
placed in a stimulating
environment
 One study of 6
individuals with HD
showed behavioral
improvement with
remotivation therapy
Van Dellen et al, Nature 2000;404:721-2
Sullivan et al. J Neurosci Nursing
2001;33:136-142
CAM for HD
Exercise
 Mechanism: explored by Spires
et al
in UK:
(J Neuroscience 2004;24:2270-6)
 Using study mice, mice were randomized
to be placed in regular vs. enriched
environments. Control mice with HD gene
were also used.
 Results: those in enriched environments
had improved coordination and had
normal levels of brain growth factors.
CAM for HD
Exercise….Does It Help in HD?
 Yes!
 Possibly
neuroprotective
 Definitely helps
symptoms of pain,
decreased balance,
walking difficulties
 Recommendation:
exercise helps!
CAM for HD
Diet and HD
CAM for HD
The HD CAG Expansion Causes a
Number of Metabolic Changes
 People with HD have decreased body
mass index (BMI) and over 3 years gain
less weight than average Americans
 Increased 24 hr energy expenditure
 Cholesterol metabolism is abnormal in
HD brain cells
 Altered glucose tolerance in people with
HD
CAM for HD
Diet Supplements in HD
 Trehalose, a naturally-occurring sugar
molecule found in shellfish, honey, and
mushrooms, helped HD mice.
Tanaka et al, Nat Med 2004;10:148-54
CAM for HD
Diet Supplements
Curcumin (spice
turmeric) reduced
protein clumping in
HD cells in culture
1. Dikshit et al, BBRC 2006.
2. Kumar et al, Methods &Findings in
Exp&Clin.Pharm. 2007
CAM for HD
More Diet Clues
 Fruits rich in polyphenols (blueberries,
cranberries, strawberries, concord grape
juice) can reduce oxidative stress and
brain inflammation and can improve
memory and motor behavior
 Another polyphenol, green tea, may also
help cells degrade abnormal protein
Joseph et al, Ann NY Acad Sci2007;1100:470-485
Kalfon et al, L Neurochem 2007;100:92-1002
CAM for HD
A Role for Chocolate in HD?
 Cocoa contains a high concentration of
flavenoids. These compounds reduce
oxidative damage in animal and cell
models.
Source: Orozco et al, J Nutri
Biochem 2003;14:104-110.
CAM for HD
More Diet Clues
 Fruits rich in polyphenols (blueberries,
cranberries, strawberries, concord grape
juice) can reduce oxidative stress and
brain inflammation and can improve
memory and motor behavior
CAM for HD
Diet in HD: What Can We
Recommend?
 Eat a diet rich in polyphenol flavinoids
(BB, other fruits, green tea, cocoa)
 Match caloric intake to energy
requirements
 Consider using trehalose or honey in place
of sugar
 Role for Turmeric…..needs more research
 Cholesterol……needs more research
CAM for HD
Supplements in HD
Coenzyme Q10
 Creatine
Omega 3 Fatty Acids
CAM for HD
Coenzyme Q10
 Mechanism: Improves energy metabolism
in mitochondria
 Source: occurs in meats and seafood
 Research: benefit seen in HD mouse model,
in brain energy metabolism in people with
HD, and showed non-significant trend* of
helping slow HD progression in HSG CAREHD study.
*Not statistically significant. HSG, Neurology 2001;57;397-404
CAM for HD
Coenzyme Q10
 Dosage: 1200-2400
mg/day
 Safety: established
 Down-side: cost
(approx. $200/month)
CAM for HD
Creatine
 Mechanism: improves energy metabolism
in body and brain
 Source: protein-derived
 Research: improved brain metabolism
and decreased blood levels of 8OH-DG;
safe and tolerable in people with HD
CAM for HD
Creatine
 Dose: 5-10 gm/day
(possibly more)
 Safety: established at
those doses
 Cost: relatively low
 Caution: kidney
disease, diabetes
Hersch et al, Neurology 2006;66:250-2
CAM for HD
Omega 3 Fatty Acids
 Mechanism: improves energy metabolism
 Source: seafood, plants (must be obtained from
diet)
 Research: Modest help in large European trial;
TREND-HD study showed no improvement in
chorea, but many study participants felt a benefit
CAM for HD
Omega 3 Fatty Acids
 Dose: 2 or more grams/day
 Safety: established, but beware of mercury
contamination
 Cost: Low
 Caution: blood thinners, avoid falls