cognitive impairments in hd - uc davis health · 5/29/2013 · omega 3 fatty acids cam for hd...

Cognitive Impairments in HD

Sarah Farias, Ph.D.

Clinical and Research Neuropsychologist

Associate Professor, Dept. of Neurology

University of California, Davis

5/29/2013

Outline

A little brain anatomy and brain changes in HD

Cognitive impairments that can occur in HD

Approaches to managing these cognitive changes


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


Brain Anatomy and Function


Motor Abilities

Executive functions:

Planning

Prioritizing

Multi-tasking

Monitoring behavior

Social/emotional

behavior

Spatial Abilities

Math

Reading

Somatosensory

Vision

Interpreting

visual input

Hearing

Language

Memory

Emotions

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

Brain Changes in HD: Cell Death in the Caudate Nucleus


Normal Advanced 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

Functions of the Frontal lobe


MOTOR COGNITIVE*

EMOTIONAL

Thinking Abilities Related to the Frontal Lobes:

Executive Functions


The ‘CEO’ of the Brain

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

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

Impairments in Executive Functions (cont.)


Problems with ‘mental flexibility’

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

Impairments in Executive Functions (cont.)


Reduced impulse control

Saying things without thinking first

Difficulty regulating eating, smoking, sexual behavior

Shop lifting

Problems with apathy

Difficulty “getting started”

Difficulty following through with tasks

Watching TV for long periods of time

Not keeping up with hygiene

Does not = laziness

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

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 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 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

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

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*

*Adapted from Jerry Lampson, www.hdlighthouse.org

CAM for HD

Spirituality

Exercise

HD Treatment

Diet and

Supplements

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

CAM for HD

Van Dellen et al, Nature 2000;404:721-2

Sullivan et al. J Neurosci Nursing

2001;33:136-142

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.

CAM for HD

Tanaka et al, Nat Med 2004;10:148-54

Diet Supplements

CAM for HD

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

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

CAM for HD

Joseph et al, Ann NY Acad Sci2007;1100:470-485

Kalfon et al, L Neurochem 2007;100:92-1002

A Role for Chocolate in HD?

Cocoa contains a high concentration of flavenoids. These compounds reduce oxidative damage in animal and cell models.

CAM for HD

Source: Orozco et al, J Nutri

Biochem 2003;14:104-110.

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 CARE-HD study.

CAM for HD

*Not statistically significant. HSG, Neurology 2001;57;397-404

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

CAM for HD

Hersch et al, Neurology 2006;66:250-2

Omega 3 Fatty Acids

CAM for HD

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

Omega 3 Fatty Acids

CAM for HD

Dose: 2 or more grams/day

Safety: established, but beware of mercury contamination

Cost: Low

Caution: blood thinners, avoid falls

cognitive impairments in hd - uc davis health · 5/29/2013 · omega 3 fatty acids cam for hd...

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