Kaplan + Sadock's Synopsis of Psychiatry, 11e

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21.3 Dementia (Major Neurocognitive Disorder)

Table 21.3-1 Possible Etiologies of Dementia

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

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