21.3 Dementia (Major Neurocognitive Disorder)
705
65 years, men have a prevalence rate of 0.6 percent and women
of 0.8 percent. At age 90, rates are 21 percent. For all of these
figures, 40 to 60 percent of cases are moderate to severe. The
rates of prevalence (men to women) are 11 and 14 percent at
age 85, 21 and 25 percent at age 90 years and 36 and 41 per-
cent at age 95 years. Patients with dementia of the Alzheimer’s
type occupy more than 50 percent of nursing home beds. More
than 2 million persons with dementia are cared for in these
homes. By 2050, current predictions suggest that there will be
14 million Americans with Alzheimer’s disease and therefore
more than 18 million people with dementia.
The second most common type of dementia is vascular
dementia, which is causally related to cerebrovascular diseases.
Hypertension predisposes a person to the disease. Vascular
dementias account for 15 to 30 percent of all dementia cases.
Vascular dementia is most common in persons between the
ages of 60 and 70 and is more common in men than in women.
Approximately 10 to 15 percent of patients have coexisting vas-
cular dementia and dementia of the Alzheimer’s type.
Other common causes of dementia, each representing 1 to
5 percent of all cases, include head trauma; alcohol-related
dementias; and various movement disorder-related dementias,
such as Huntington’s disease and Parkinson’s disease. Because
dementia is a fairly general syndrome, it has many causes, and
clinicians must embark on a careful clinical workup of a patient
with dementia to establish its cause.
Etiology
The most common causes of dementia in individuals older than
65 years of age are (1) Alzheimer’s disease, (2) vascular demen-
tia, and (3) mixed vascular and Alzheimer’s dementia. Other
illnesses that account for approximately 10 percent include
Lewy body dementia; Pick’s disease; frontotemporal dementias;
normal-pressure hydrocephalus (NPH); alcoholic dementia;
infectious dementia, such as HIV or syphilis; and Parkinson’s
disease. Many types of dementias evaluated in clinical set-
tings can be attributable to reversible causes, such as metabolic
abnormalities (e.g., hypothyroidism), nutritional deficiencies
(e.g., vitamin B
12
or folate deficiencies), or dementia syndrome
caused by depression. See Table 21.3-1 for a review of possible
etiologies of dementia.
Dementia of the Alzheimer’s Type
In 1907, Alois Alzheimer (Fig. 21.3-1) first described the condi-
tion that later assumed his name. He described a 51-year-old
woman with a 4½-year course of progressive dementia. The
final diagnosis of Alzheimer’s disease requires a neuropatho-
logical examination of the brain; nevertheless, dementia of the
Alzheimer’s type is commonly diagnosed in the clinical setting
after other causes of dementia have been excluded from diag-
nostic consideration.
Genetic Factors.
Although the cause of dementia of the
Alzheimer’s type remains unknown, progress has been made in
understanding the molecular basis of the amyloid deposits that
are a hallmark of the disorder’s neuropathology. Some studies
have indicated that as many as 40 percent of patients have a
family history of dementia of the Alzheimer’s type; thus, genetic
Table 21.3-1
Possible Etiologies of Dementia
Degenerative dementias
Alzheimer’s disease
Frontotemporal dementias (e.g., Pick’s disease)
Parkinson’s disease
Lewy body dementia
Idiopathic cerebral ferrocalcinosis (Fahr’s disease)
Progressive supranuclear palsy
Miscellaneous
Huntington’s disease
Wilson’s disease
Metachromatic leukodystrophy
Neuroacanthocytosis
Psychiatric
Pseudodementia of depression
Cognitive decline in late-life schizophrenia
Physiologic
Normal-pressure hydrocephalus
Metabolic
Vitamin deficiencies (e.g., vitamin B
12
, folate)
Endocrinopathies (e.g., hypothyroidism)
Chronic metabolic disturbances (e.g., uremia)
Tumor
Primary or metastatic (e.g., meningioma or metastatic breast or
lung cancer)
Traumatic
Dementia pugilistica, posttraumatic dementia
Subdural hematoma
Infection
Prion diseases (e.g., Creutzfeldt-Jakob disease, bovine
spongiform encephalitis, Gerstmann-Sträussler syndrome)
Acquired immune deficiency syndrome (AIDS)
Syphilis
Cardiac, vascular, and anoxia
Infarction (single or multiple or strategic lacunar)
Binswanger’s disease (subcortical arteriosclerotic
encephalopathy)
Hemodynamic insufficiency (e.g., hypoperfusion or hypoxia)
Demyelinating diseases
Multiple sclerosis
Drugs and toxins
Alcohol
Heavy metals
Irradiation
Pseudodementia due to medications (e.g., anticholinergics)
Carbon monoxide
factors are presumed to play a part in the development of the
disorder, at least in some cases. Additional support for a genetic
influence is the concordance rate for monozygotic twins, which
is higher than the rate for dizygotic twins (43 percent vs. 8 per-
cent, respectively). In several well-documented cases, the dis-
order has been transmitted in families through an autosomal
dominant gene, although such transmission is rare. Alzheimer’s
type dementia has shown linkage to chromosomes 1, 14, and 21.
amyloid
precursor
protein
.
The gene for amyloid precursor
protein is on the long arm of chromosome 21. The process of differential
