Chapter 193

Dementia

Karen Dick

Definition and Epidemiology

Most people enjoy a fruitful and productive period during their later years. However, for 5% to 10% of the population older than 65 years and 45% to 50% of the population older than 85 years, these years are associated with a serious form of cognitive impairment known as dementia.¹ It is estimated that more than 5 million people in the United States—regardless of race, gender, or socioeconomic status—have the most common type of dementia, Alzheimer disease. The Alzheimer’s Association estimates that nearly 16 million Americans will have dementia of the Alzheimer type by 2050 unless a cure is found.¹ Alzheimer disease is the sixth leading cause of death in the United States and the only cause of death among the top 10 in the United States that cannot be prevented, cured, or even slowed.¹

Dementia is often the reason for institutionalization; it accounts for more than 50% of all nursing home admissions, and according to 2010 data, up to 50% of patients residing in nursing homes have dementia.² It has long been a common belief that memory loss is an inevitable and incurable part of the aging process, making any clinical intervention useless. However, with the recent advances in research, as evidenced by numerous clinical trials and new drug therapies, early detection, treatment, education, and support for families are even more critical.

The term dementia includes several symptoms, including a progressive loss of memory and behavioral changes, which together interfere with independence in activities of daily living. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, defines dementia under the heading of Major or Mild Neurocognitive Disorders and further divides by type; examples include the following:

• Neurocognitive Disorder Due to Alzheimer Disease

• Frontotemporal Neurocognitive Disorder

• Neurocognitive Disorder with Lewy Bodies

• Vascular Neurocognitive Disorder

• Neurocognitive Disorder Due to Traumatic Brain Injury

• Substance/Medication-Induced Neurocognitive Disorder

The diagnostic criteria for Alzheimer Disease and Vascular neurocognitive disorders are described in Boxes 193-1 and 193-2.³ These are the two most common types of dementia and account for about 80% to 90% of all dementias in older adults.⁴

Box 193-1

Diagnostic Criteria for Major and Mild Neurocognitive Disorder Due to Alzheimer Disease

A. The criteria are met for major or mild neurocognitive disorder.

B. There is insidious onset and gradual progression of impairment in one or more cognitive domains (for major neurocognitive disorder, at least two domains must be impaired).

C. Criteria are met for either probable or possible Alzheimer’s disease as follows:
For major neurocognitive disorder:
Probable Alzheimer’s disease is diagnosed if either of the following is present; otherwise, possible Alzheimer’s disease should be diagnosed.

1. Evidence of a causative Alzheimer’s disease genetic mutation from family history or genetic testing.

2. All three of the following are present:

a. Clear evidence of decline in memory and learning and at least one other cognitive domain (based on detailed history or serial neuropsychological testing).

b. Steadily progressive, gradual decline in cognition, without extended plateaus.

c. No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline).

For mild neurocognitive disorder:
Probable Alzheimer’s disease is diagnosed if there is evidence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history.
Possible Alzheimer’s disease is diagnosed if there is no evidence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history, and all three of the following are present:

1. Clear evidence of decline in memory and learning.

2. Steadily progressive, gradual decline in cognition, without extended plateaus.

3. No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological or systemic disease or condition likely contributing to cognitive decline).

D. The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

Box 193-2

Diagnostic Criteria for Major or Mild Vascular Neurocognitive Disorder

A. The criteria are met for major or mild neurocognitive disorder.

B. The clinical features are consistent with a vascular etiology, as suggested by either of the following:

1. Onset of the cognitive deficits is temporally related to one or more cerebrovascular events.

2. Evidence for decline is prominent in complex attention (including processing speed) and frontal-executive function.

C. There is evidence of the presence of cerebrovascular disease from history, physical examination, and/or neuroimaging considered sufficient to account for the neurocognitive deficits.

D. The symptoms are not better explained by another brain disease or systemic disorder.
Probable vascular neurocognitive disorder is diagnosed if one of the following is present; othenwise possible vascular neurocognitive disorder should be diagnosed:

1. Clinical criteria are supported by neuroimaging evidence of significant parenchymal injury attributed to cerebrovascular disease (neuroimaging-supported).

2. The neurocognitive syndrome is temporally related to one or more documented cerebrovascular events.

3. Both clinical and genetic (e.g., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) evidence of cerebrovascular disease is present.

Possible vascular neurocognitive disorder is diagnosed if the clinical criteria are met but neuroimaging is not available and the temporal relationship of the neurocognitive syndrome with one or more cerebrovascular events is not established.

Mild Cognitive Impairment

Mild cognitive impairment (MCI) is thought to be a transitional state between normal aging and dementia. Patients may have one of two types: amnestic, characterized by deficits in memory; or nonamnestic, which involves impairments in other cognitive functions. Because it is believed that these patients may progress to dementia at a rate of 10% to 15% a year, MCI is considered a risk factor for all types of dementia, and these patients need close monitoring and follow-up.⁵

Pathophysiology

Alzheimer Disease

Alzheimer disease is characterized by amyloid plaques and neurofibrillary tangles. Examinations of the brains of patients with Alzheimer disease show atrophy of the cerebral cortex that is usually diffuse but may be more pronounced in the frontal, temporal, and parietal lobes.⁶ The degree of atrophy may not correlate with the degree of cognitive impairment. The amyloid hypothesis presumes a central role for abnormal amyloid processing and remains the most widely embraced causative theory.⁶ Biochemically, there is disruption to the cortical pathways involved in catecholaminergic, serotonergic, and cholinergic transmission. There is a reduction of choline acetyltransferase, an enzyme found only in cholinergic neurons. Advances in genetic research have included the identification of apolipoprotein E, a protein involved in cholesterol transport linked to Alzheimer disease, and the identification of the β-amyloid gene on chromosome 21. Researchers continue to explore the role of inflammation and oxidative stress and their effects on neuronal health. Clinical trials are under way investigating the effects of antiamyloid therapies including antibody-stimulating vaccines and other drug compounds.

Vascular Dementia

Multiple areas of focal ischemic change characterize vascular dementia, formerly known as multi-infarct dementia. The defining lesion is the lacunar infarct. Lacunae are defined as gaps, missing areas, or holes.⁷ The infarctions occur in tiny arteries deep in the brain. Patients with hypertension, diabetes, hyperlipidemia, or peripheral vascular occlusive diseases are at particular risk.⁴ Patients may have a mixed dementia with both Alzheimer and vascular types.

Lewy Body Dementia

Lewy body dementia is characterized by the presence of Lewy bodies in the brain. These are proteins that enter neurons and cause cell degeneration and death. There is a loss of dopamine-producing neurons, similar to that seen in Parkinson disease, and a loss of acetylcholine, similar to that seen in Alzheimer disease.⁸

Pseudodementia

Depression in older adults can lead to memory loss, attention deficits, and problems with initiation, and is referred to as pseudodementia. Clinicians need to be aware that depression may go untreated, especially with patients not complaining of sadness or anxiety, which may lead to impairments in cognition. A complicating factor is that older adults with depression may be at increased risk of dementia. To complicate this more, depression may be a common early dementia presentation.⁹ A therapeutic trial of antidepressants and subsequent reevaluation of mood and cognition should be pursued to appropriately diagnose one or both conditions.

Clinical Presentation

Memory loss, personality changes, language disturbances, and problems with independent activities of daily living are common presenting symptoms of dementia. A concerned family member or friend typically makes the initial presentation to a health care provider. It may take months to years for family members to seek medical attention because subtle changes in cognition may be overlooked or attributed to old age. Patients with dementia do not typically worry about what is wrong with them. These patients often have little understanding of the seriousness of their symptoms or of safety concerns (e.g., driving, cooking). On the other hand, patients with depression or benign forgetfulness often appear to the health care provider to be overly concerned about minor symptoms (e.g., forgetting a name, misplacing keys). An anecdotal finding in primary care is that patients worried about memory problems often have only minor problems, whereas patients who seem unconcerned pose a major worry to providers.

Patients with Lewy body dementia may have visual hallucinations, motor impairments, postural instability, and sleep disturbances. They also show an increased sensitivity to neuroleptics; these are the patients who, when given drugs such as haloperidol for acute agitation, get worse.⁸

Alzheimer disease is commonly divided into three stages: early, middle, and late (Box 193-3). The initial symptom is typically short-term memory loss. The earliest stage is often accompanied by symptoms of anxiety and depression. Word finding and naming problems may emerge as symptoms progress. The second stage is characterized by a worsening of memory and language as well as judgment. Disorientation to time and place is common. There may be neuropsychiatric symptoms, including paranoia, hallucinations, and delusional thinking. Urinary incontinence may be a problem. The final stage is characterized by motor rigidity, prominent neurologic abnormalities including apraxia and agnosia, severe cognitive and language impairment, and death. The average duration of the disease from diagnosis until death is 9 years.⁹ Staging of a patient’s disease based on clinical presentation and examination can be helpful to patients and families in planning subsequent care and treatment.

Box 193-3

Stages of Alzheimer Disease

Early-Stage Dementia