Chapter 3 – Neurodegenerative Disorders
Neurodegenerative disorders: disorders that involve progressive loss of function or
destruction of neurons or various structures of the brain
Acquired disorders: disorders caused by an accident, insult, or disease process coming
from a source outside the cortex
Degenerative disorders: difficulties with destruction of neurons and/or specific areas
within the central nervous system
• In many cases, the loss of neurons/tissue is not reparable and the loss of ability
Def.: damage within the cerebral cortex, which leads to symptoms of dementia.
Dementia is usually described with behaviours falling into 3 stages
1. Behaviours that may deviate from the norm for the individual. The individual may
not be aware of this
a. Example: small changes in personality and memory lapses
2. Individual often notices memory problems and tries to conceal them from others.
Confabulation (individual makes up a story to account for memory loss) may
a. As stage 2 progresses, the individual may become geographically lost
b. May engage in activities that are dangerous to self or others
c. Sundowning: worsening of symptoms as the day progresses
d. Families begin to consider placement in treatment facilities
3. Serious cognitive deterioration along with problems with self-care
a. Many find that individual requires care outside family environment
People don’t usually die from dementia but from something else that takes advantage of
a nonintact central nervous system.
• May be unable to fight off viruses
• Most frequent cause of death is pneumonia
Affects 5-8% of people older than 65 and 25-50% of people older than 85. Alzheimer’s Type Dementia
Def.: dementia characterized by neurofibrillary tangles and amyloid plaques; diagnosis
cannot be made until autopsy but is termed Alzheimer’s type based on behavioural
• Neurofibrillary tangles: composed of tau protein; tangles of dead tissue in the
brain. Develop when microtubules become twisted. Volume of tangles obstructs
living tissue and often strangle it.
o Tau: protein that maintains microtubules structure but is altered, allowing
tubules to twist. Believed to develop from abnormal phosphorylation
• Amyloid plaques: deposits of aluminum silicate and amyloid peptides (beta-
amyloid) believed to cause loss of neurons and vascular damage. Obstruct
• These plaques/tangles normally appear in aging people but Alzheimer’s is
diagnosed by the extent of these and the regions of the brain that they gravitate
Loss of neurons is a common feature, especially in the temporal area.
• If neurons can’t communicate with major memory areas within cortex, significant
memory loss may occur.
Loss of neurons also leads to changes in anatomical structure, may point to
enlargement of ventricles in Alzheimer’s disease.
Present in 10% of people aged 65+ and 25% over 80. Also has inherited genetic
• If a person has a first-degree relative with the disease, it doubles their chance of
acquiring the disease.
Three well-established risk factors for Alzheimer’s:
• The gene for the protein apolipoprotein E (Apo E) on chromosome 19. Is a
naturally occurring protein, helps to carry phospholipids and cholesterol within
o The E4 allele (any one of a number of viable DNA codings that occupy a
given position on a chromosome) has been linked to various disorders
• Down syndrome. Almost all individuals with this show mental and physical
deterioration characteristic of Alzheimer’s if they live longer than 30-40 years. Other factors:
• Being female
• Lower levels of education
• Exposure to aluminum in drinking water
• Traumatic brain injury – controversial. The more serious an injury, the more likely
the person will develop the disease.
• Low level of estrogen in postmenopausal women – controversial. May be
confounded with educational level and socioeconomic status
Most distinguishing cognitive feature of Alzheimer’s is severe verbal memory difficulties.
• Difficulty is in all stages of memory
• Other issues:
o Psychomotor performance
o Language/speech fluency
o Complex reasoning
Treatment for Alzheimer’s:
• Drinking red wine as preventative (antioxidants have protective effect)
• Medications that stop the development of amyloid plaques
• Cognitive deficits treatment is usually with anticholinesterase inhibitors that
enhance cholinergic function
o People either respond to this or they don’t
• May use typical or atypical antipsychotic medications
Degenerative disorders of the frontal and temporal lobes. The rest of the cortex remains
• Slow onset and progression
• Usually between 40-65 years of age
Symptoms are very similar to Alzheimer’s and, in later stages, almost indistinguishable.
Differentiation: • Changes in social behaviour and personality
• Lack of insight
• Stereotypic behaviours – repeating of a behavioural sequence
• Eating a great deal of food
• Speech and language changes
• Extrapyrimidal symptoms
• Primitive reflexes
Etiology is unknown but 40-50% if cases are transmitted by autosomal dominate
inheritance = dominant non-sex-linked gene
• Greater than average incidence of brain trauma 4 years prior to occurrence of
Before, was called Pick’s disease – that is now thought to be a subtype of FTD. Set
apart from other FTDs by Pick bodies: composed of tau protein and shaped differently
than neurofibrillary tangles
Dementia with Lewy Bodies
About 20% of patients with dementia.
Symptoms include progressive dementia, extrapyramidal signs similar to Parkinson’s,
visual hallucinations, delusions, and possibly severe cognitive fluctuations.
More rapid decline than other dementias.
Presence of Lewy bodies: protein deposits throughout the cortex, paralimbic area, and
in the substantia nigra.
Improvement has been shown with using cholinesterase inhibitors
Affect subcortical brain structures. The behavioural changes that differentiate from
1. Cognitive slowing with problems in attention and concentration, executive
disturbances including impaired concept manipulation, visuospatial
abnormalities, and memory difficulties that affect retrieval
2. Absence of aphasia (loss of expressive or receptive language), apraxia (inability
to perform purposeful movements), and agnosia (inability to recognize sensory
3. Emotional features including apathy, depression, and personality changes. Have movement difficulties – extrapyramidal motor system: modulates movement and
maintains muscle tone and posture.
Def.: Movement disorder with attendant symptoms.
Involuntary tremulous motion with lessened muscle power. May include difficulties
moving from resting to walking (vice versa), tendency to bend forward while walking,
and cognitive/emotional sequelae.
• Not all patients exhibit these
• Almost always present is ‘resting tremor’ which disappears during movement and
• Another classic symptom is ‘masked faces’, a lack of facial expressions
• Depression is one of most common symptoms but severity appears unrelated to
severity of motor symptoms
The disease is associated with the depletion of the neurotransmitter dopamine in the
basal ganglia, subthalamic nucleus, substantia nigra, and the connections between
Etiology is unknown. Typically affects individuals in their fifties.
• There may be genetic inheritance
• May be related to viral encephalitis, drugs with dopamine antagonistic properties,
toxic substances, and vascular disease.
PD does have an incidence of dementia that ranges from 2-93%.
• Medical focuses on the alleviation of symptoms or slowing disease progression
o L-Dopa is used to replace dopamine depletion in the subtantia nigra
• Surgical treatments include lesions or placing a deep brain stimulator in the
regions of the globus pallidus, subthalamic nuclei, or ventral intermediate
Anatomically caused by atrophy of the GABAergic neurons fo the caudate nucleus and
putamen in the corpus striatrum.
• Gamma-aminobutyric acid (GABA) is the most common inhibitory
neurotransmitter. • Atrophy may also affect the cerebellum, thalamic nucleu, and other subcortical
tissue. Reported effects on the basal ganglia as well.
Steadily progressive disease, tends to affect individual between 10-20 years of age.
• First symptoms are mild and often ignored
• As motor symptoms are involved, the disease becomes visible to the individual
• Pneumonia is most common cause of death
Hereditary condition – passes from generation to generation
• Caused by an excess number of trinucleotide CAG repeats (cystosine, adenine,
and guanine) on chromosome 4
• Is an autosomal dominant disease – half of all offspring of a carrier parent will
acquire the disease if they live long enough
• Affects more Caucasians
Treatment is usually palliatative. Neuroleptic medications are often used to deal with
Progressive Supranuclear Palsy
Also known as Steele-Richardson-Olszewski disorder.
Classic feature is an inability to look downward.
• Similar motor/cognitive/emotional disturbances as with other dementias
• Progression of cognitive decline appears to be greater and is consistent with
degeneration of both cortical and subcortical regions
• Sites of lesions are in the upper brain stem to the basal ganglia and may include
the limbic structures and basal ganglia
• Degeneration appears to disconnect ascending pathways from these structures
to the prefrontal cortex
Nonfamilial condition, tends to develop in 60s. May have connection to environmental
Has limited response to dopaminergic or anticholonergic drugs.
Progressive Disorders of the Central Nervous System
Def.: Disease caused by destruction of the myelin sheath that covers the axons. At the
demyelinated sites, multiple discrete plaques are formed by astrocytes. Classic symptoms:
• Lack of coordination
• Gait disturbances
• Bladder and bowel difficulties
• Sexual dysfunction
• Sensory changes
• Heat sensitivity
Cognitive impairment is evident in 40-60% of patients. Memory is one of most
commonly affected areas. The extent of cognitive deficits is related to location and
extent of damage.
Tends to follow one of several courses:
• Relapsing-remitting: most common. Characterized by clearly defined diseases
relapses. Recovery can be full or with residual deficit. No progression of disease
• Secondary-progressive: second most common. First characterized by relapsing-
remitting course then progression. Relapses and remissions may or may not
• Primary-progressive: third most common. Unremitting disease progression from
onset for most patients but occasional stabilization and improvement in others.
No clear relapse.