C h a p t e r 3 7
Disorders of Brain Function
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OtherTypes of Dementia
Cerebrovascular injury, brain tissue atrophy, alcohol-
ism, and genetic disorders can also result in dementia.
Vascular Dementia
Vascular dementia is caused by brain injury resulting
from ischemic or hemorrhagic damage. Vascular demen-
tia is the second most common cause of cognitive impair-
ment in the elderly. The incidence is closely associated
with hypertension, but also with arrhythmias, stroke,
peripheral vascular disease, lipid abnormalities, and dia-
betes mellitus.
73–75
The usual onset is between the ages of
55 and 70 years, and more men are affected than women.
The vessel disorders associated with vascular dementia
include atherosclerosis, small vessel disease, cerebral amy-
loid angiopathy, brain infarcts, and cerebral hemorrhage.
In addition to the impact of cerebral vascular lesions on
dementia, the association between Alzheimer disease and
vascular dementia points to a possible pathogenic link
between AD and blood vessel causes of dementia.
Slowness in psychomotor functioning is a main clini-
cal feature of this dementia, and symptoms of depression
are present in up to 60% of patients with this disease.
4
The onset may be gradual or abrupt, the course usually
is a stepwise progression, and there are focal neurologic
symptoms related to local areas of infarction.
Frontotemporal Dementia
Frontotemporal dementia (FTD) refers to a group of
disorders associated with atrophy of the frontal and
anterior temporal lobes of the brain.
76,77
Originally
known as
Pick disease,
FTD now refers to a syndrome
that includes primary progressive aphasia, cortico-
basal degeneration, progressive supranuclear palsy, and
semantic dementias. The disease often begins between
45 and 64 years of age, and is one of the most common
forms of dementia in persons younger than 65 years.
The pathophysiology of FTD is not well understood.
The disease is characterized by extensive atrophy of
the frontotemporal regions, with the involved cortex
being severely depleted of neurons. Most recently,
mutations of the prograndin gene on chromosome
17 have been associated with intranuclear inclusions
found in the brain tissue of persons with the disorder.
Prograndin is a growth factor with multiple functions,
including neuronal survival. Other than mutations
linked to chromosome 17, several other chromosomes
have been implicated in FTD, including mutations in
chromosomes 3 and 9.
There are two distinct clinical presentations of FTD:
behavior and language. The former is more common,
with behavioral presentations of disinhibited and impul-
sive actions or apathy, with inappropriate social behav-
ior. Unlike Alzheimer disease, which usually begins with
memory difficulties, FTD begins with very disruptive
behaviors that can be quite extreme, and can be misdi-
agnosed as schizophrenia or psychotic depression. The
second type of FTD behavior involves disturbances in
understanding or expressing language.
Diagnosis of FTD is based on evidence of cognitive
impairment and exclusion of other illnesses that cause
cognitive and behavioral deficits. Neuroimaging can be
helpful in distinguishing FTD from other types of cogni-
tive disorders. Typically, structural imaging shows ante-
rior temporal and frontal lobe atrophy.
There is no specific cure for FTD. Treatment is focused
on symptom management and support for patients, fam-
ilies, and caregivers. Current research focuses on molec-
ular biology to better understand the underlying disease
and the potential for identification of novel treatments,
particularly disease-modifying treatments.
Wernicke-Korsakoff Syndrome
Wernicke-Korsakoff syndrome most commonly results
from chronic alcoholism. Wernicke disease is charac-
terized by acute weakness and paralysis of the extra-
ocular muscles, nystagmus, ataxia, and confusion.
4
The
affected person also may have signs of peripheral neu-
ropathy. The person has an unsteady gait and complains
of diplopia. There may be signs attributable to alcohol
withdrawal such as delirium, confusion, and hallucina-
tions. This disorder is caused by a deficiency of thiamine
(vitamin B
12
), which directly interferes with produc-
tion of glucose, the brain’s main nutrient. Many of the
symptoms are reversed when nutrition is improved with
supplemental thiamine.
The Korsakoff component of the syndrome involves
the chronic phase with severe impairment of recent
memory. There often is difficulty in dealing with abstrac-
tions, and the person’s capacity to learn is defective.
Confabulation (i.e., recitation of imaginary experiences
to fill in gaps in memory) probably is the most distinc-
tive feature of the disease. Polyneuritis also is common.
Unlike Wernicke disease, Korsakoff psychosis does not
improve significantly with treatment.
Huntington Disease
Huntington disease (HD) is a hereditary disorder char-
acterized by chronic progressive chorea, psychological
changes, and dementia.
1,4,78–81
Although the disease is
inherited as an autosomal dominant disorder, the age of
onset most commonly is in the fourth and fifth decades.
By the time the disease has been diagnosed, the person
often has passed the gene on to his or her children.
Approximately 10% of HD cases are juvenile onset.
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Children with the disease rarely live to adulthood.
Huntington disease is caused by a polyglutamine
trinucleotide repeat expansion in the HD gene. The
HD gene, located on chromosome 4, encodes a protein
known as
huntingtin
.
1,78–80
Normal HD genes contain
6 to 35 copies of the trinucleotide repeat; an expan-
sion of repeats beyond this level is associated with dis-
ease. There is an inverse relationship between repeat
number and age of onset, such that longer repeats are
associated with earlier onset. Repeat expansions occur
during spermatogenesis, so that paternal transmission
is associated with early onset in the next generation.
Although the biologic function of normal huntingtin
remains unknown, there is little evidence to suggest
