common brain disorders in...

Common Brain Disorders in Seniors

Robbin Gibb, PhD Associate Professor

Canadian Centre for Behavioural

Neuroscience University of Lethbridge, Canada

The Roots of Brain Health and Disease form in Childhood

The Roots of Brain Health and Disease form in Childhood

• Adverse Childhood Experience Study – 17,000+ middle-aged adults in USA

•  Findings: •  1. ACEs are more common than

recognized •  2. ACEs have a powerful relation to adult

health 50 yrs later.

Turning Gold into Lead

Examples of ACEs: -family violence: spousal or child related -parental alcohol or drug addictions -sexual, physical, or emotional abuse -growing up in a household where someone is in jail -parental chronic depression or other ‘mental’ illness -loss of one parent for whatever reason

Outcomes after age 55

Health in midlife is related to ACEs

-smoking or other addictions -heart and lung disease -depression -diabetes -hypertension -macular degeneration -psoriasis -suicide (or attempted) -etc

The increase in incidence varies from about 3X for smoking to 50X for drug addiction, and 50X for attempted suicide with more than 2 ACE’s

Which Mental Diseases are Most Common

Amongst Seniors?

Depression Stroke Dementias (Reversible, AD, PD)

What is Depression?

• Major depression is a mood disorder characterized by prolonged feelings of worthlessness and guilt

Symptoms of Depression

• Disruption of normal eating habits

• Sleep disturbances • Slowing of behavior

Depression

• Most common mental disorder in people age 65 or older

• Over 15% of the population report severe symptoms

• Only 3% have major depression diagnoses

Depression

• Depression increases likelihood of death 2-3X

• Amplifies deficits associated with physical illness

•  Interferes with rehab and fitness • Contributes to cognitive decline

Risk for Depression is Higher for

• Seniors with chronic disease • Those in long-term care/nursing

homes • Those providing care for a family

member

Kolb & Whishaw, An Introduction to Brain and Behavior, Fourth Edition - Chapter 5


Neurobiology of Depression •  Antidepressant drugs act to increase levels

of norepinephrine and serotonin/ •  There is little evidence, however, that low

levels of these neurotransmitters cause depression. – Lowering levels of these neurotransmitters in

healthy adults does not produce depression. – Antidepressant medications alter the levels of

these neurotransmitters within days, but it takes weeks for the drugs to start relieving depression.


Neurobiology of Depression Duman (2004)

– Suggested that depression may involve low levels of neurotrophic factors

– Brain-derived neurotrophic factor (BDNF) is down-regulated by stress and up-regulated by antidepressant medications.

– Antidepressant medications may increase levels of BDNF.


Mood and Reactivity to Stress HPA Axis

• Hypothalamic-pituitary-adrenal circuit that controls the production and release of hormones related to stress

– Chronic stress can lead to oversecretion of cortisol, associated with depression in adulthood • 45% of adults with depression lasting more

than 2 years experienced abuse, neglect, or parental loss as children


How is Depression Treated?

•  The best treatment need not be direct biological intervention. – Cognitive-behavioral therapy (CBT)

• Problem-focused, action-oriented, structured treatment for eliminating dysfunctional thoughts and maladaptive behavior

• Arguably the best therapy for depression


•  Exercise


•  Drugs- SSRI’s (carefully monitored) •  Seniors are more sensitive to side effects

What can Friends and Family Do?

•  Include in outings •  Engage in regular social activities. Insist

on inclusion •  Healthy meals •  Encourage adherence to treatments •  Make sure medications are used as

prescribed •  Watch for suicide signs

What is Stroke?

•  Stroke is the disruption of blood flow to an area or areas in the brain. – The disruption can result from a clot – Burst vessel – Migraine

What is the Incidence of Stroke?

– 62,000 strokes in Canada each year – 315,000 Canadians living with the effects

of stroke Stroke is the leading cause of death and disability amongst adults (not all of whom are Seniors)

Types of Stroke

•  Transient Ischemic attacks (TIA’s) •  Silent Strokes •  Ischemic Strokes •  Hemorrhagic * NO TPA

When is Stroke Most Likely to Occur?

•  Winter •  Mondays (particularly working men) •  Between 8:00 am and noon •  At home

Strokes can and do occur at any time

What are the symptoms of Stroke?

•  Weakness: sudden loss of strength or sudden numbness in face, arm or leg even if temporary

•  Trouble speaking: Sudden difficulty in speaking or understanding or sudden confusion even if temporary

•  Vision Problems: Sudden trouble with vision even if temporary

What are the symptoms of Stroke?

•  Headache: Sudden severe and unusual headache

•  Dizziness: Sudden loss of balance, especially with any of the above signs

FAST

•  F: FACE- is it drooping? •  A: ARMS -can you raise both? •  S: SPEECH -is it slurred or

jumbled? •  T: TIME -call 911 right away

TIME IS BRAIN !!

Effects of Stroke •  Release of massive amounts of the NT

glutamate causing over-excitation of neurons •  Exuberant excitation causes changes in

protein production which causes further insult to neurons

•  Energy crisis ensues as mitochondria reduce their production of ATP


Effects of Stroke •  Neural shock occurs (diaschisis)

– Areas distant from the damage are functionally depressed; areas related to the damaged region suffer sudden changes in operations which confuses cell function

•  May be followed by changes in the metabolism of the injured hemisphere, glucose utilization, or both, which may persist for days – Metabolic changes can have severe effects on

the functioning of otherwise normal tissue. Kolb & Whishaw, An Introduction to Brain and Behavior, Fourth Edition - Chapter 16

Results of Ischemia


What are the treatments for Stroke?

•  Immediate response and quick medical attention can lead to better outcomes

•  Clot-busting drug called tissue plasminogen activator –  t-PA must be administered within 3 to 5

hours to be effective. –  tPA is currently the only approved

medication to give for ischemic stroke

•  Surgery •  Nonsurgical techniques (catheters) •  Endovascular thrombectomy (Hill,

Demchuk)


•  Surgery •  Nonsurgical techniques (catheters) •  Endovascular thrombectomy (Hill,

Demchuk) In clinical trials •  Neuroprotectant

– Drug used to try to block the cascade of poststroke neural events


•  Promising work has been done with: •  Cooling •  Inducing hibernation like states •  Electrical/ Magnetic stimulation

of brain

What rehabilitation is available for Stroke?

• Physical Therapy • Occupational Therapy • Speech Therapy •  Therapy for Mental Health

Constraint-induced therapy

•  Intact limb is held in a sling for several hours per day, forcing the patient to use the impaired limb

•  An important component of these treatments is a post-treatment contract in which the patients continue to practice after the formal therapy is completed.



Dementias

•  Deficit in memory and one other cognitive domain

•  Deficits interfere with social or occupational functioning

•  Evidence of systemic or brain disorder that could be the cause


Reversible Dementias

•  Some medications- any drug with cholinergic activity

•  Alcohol abuse •  Tumors or subdural hematoma •  Anemia (B12 or Folate deficiency) •  Infections or inflammation •  Depression •  Disease of heart, lungs, liver, OR adrenal,

thyroid, pituitary glands


Alzheimer’s Disease •  Approximately 65% of dementia cases •  Cause is unknown, but proposed causes

include: – Genetic predisposition; environmental toxins;

high levels of trace elements, such as aluminum in the blood; an autoimmune response; a slow-acting virus; and reduced blood flow to the hemispheres


Alzheimer’s Disease •  Anatomical Correlates

– Neuritic (amyloid) plaque •  Located mostly in the cerebral cortex •  Also found in non-Alzheimer dementia patients

– Neurofibrillary tangles •  Paired helical filaments found in the cerebral cortex

and the hippocampus •  Also found in patients with Down syndrome,

Parkinson’s disease, and other types of dementia


Alzheimer’s Disease •  Anatomical Correlates

– Cortical Degeneration •  Most affected areas are the limbic cortex, inferior

temporal cortex, and posterior parietal cortex •  The entorhinal cortex (link between neocortex and

hippocampus) shows clearest evidence for cell loss, which may explain why memory problems occur early in the disease.

•  The primary sensory and motor areas are spared.

Cell Death in Alzheimer’s Disease

Cortical Degeneration in Alzheimer’s Disease



Alzheimer’s Disease •  Cortical Degeneration

– Cerebral atrophy may be due in large part to the loss of dendritic arborization.

– Loss of neurotransmitters •  Acetylcholine •  Noradrenaline •  Dopamine •  Serotonin •  NMDA and AMPA glutamate receptors


Parkinson’s Disease •  Related to the degeneration of the substantia

nigra and to the loss of the neurotransmitter dopamine.

•  Despite a common site of damage, symptoms vary enormously among people.

•  Many symptoms resemble the changes in motor activity that take place as a consequence of aging.


Parkinson’s Disease •  Positive Symptoms

– Tremor at rest – Muscular rigidity (increased muscle tone) –  Involuntary movements

•  Akathesia: Small, involuntary movements or changes in posture; motor restlessness

•  Occulogyric crisis: involuntary turns of the head and eyes to one side


Parkinson’s Disease •  Negative Symptoms

– Disorders of posture (fixation and equilibrium) – Disorders of righting (e.g., standing up) – Disorders of locomotion

•  Festination: tendency to engage in a behavior, such as walking, at faster and faster speeds

– Speech disturbances (e.g., loss of prosody) – Akinesia (poverty or slowness of movement)


Parkinson’s Disease •  Cognitive symptoms

– Can include impoverishment of feeling, libido, motive, and attention; cognitive slowing

•  Causes of Parkinsonism – Loss of cells in the substantia nigra, which may

be caused by diseases such as encephalitis, syphillis, drugs (e.g., MPTP), or unknown causes


Parkinson’s Disease •  Treatment

– Behavioral •  Physical therapy is often helpful

– Pharmacological •  Increase levels of dopamine (e.g., dopamine agonists

such as L-dopa) •  Suppress the activity of structures that show

heightened activity in the absence of adequate dopamine action (e.g., anticholinergic drugs)


Parkinson’s Disease – Surgical

•  A lesion of the internal part of the globus pallidus (GPi) can reduce rigidity and tremor

•  Hyperactivity of GPi neurons can also be reduced neurosurgically by electrically stimulating the neurons via deep brain stimulation.

– Transplantation •  Transplant embryonic dopamine-producing cells or

multipotential stem cells into the basal ganglia •  Highly experimental


Are Parkinson’s and Alzheimer’s Aspects of One

Disease? •  Both diseases are characterized by Lewy

bodies. – Circular fibrous structure found in several

neurodegenerative disorders; forms within the cytoplasm of neurons and is thought to result from abnormal neurofilament metabolism

Age-Related Cognitive Loss •  Aging is associated with declines in

perceptual functions, especially vision, hearing, and olfaction, and declining motor, cognitive, and executive (planning) functions. – Decrease in white-matter volume probably

related to myelin loss •  Engaging in cognitively stimulating activities

can keep neural networks and general cognitive function from declining with age. Kolb & Whishaw, An Introduction to Brain and Behavior, Fourth Edition - Chapter 16

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