Dementia

Essentials of Diagnosis

• Progressive decline of intellectual function

• Loss of short-term memory and at least one other cognitive deficit

• Deficit severe enough to cause impairment of function

• Not due to delirium or psychiatric disease

• Major risk factors

  • Age

  • Family history

  • Lower educational level

  • Diabetes mellitus

  • Cigarette smoking

  • Hypertension

  • Obesity

  • History of significant head injury

  • Hearing loss

  • Female sex

• Vitamin D deficiency and chronic sleep deprivation may also increase the risk for dementia

General Considerations

• Defined as a progressive, acquired impairment in multiple cognitive domains, at least one of which is memory, that is severe enough to compromise work or social life

• "Mild cognitive impairment" describes a decline that has not resulted in a change in the level of function

• Patients have little cognitive reserve and can have acute cognitive or functional decline with a new medical illness

• Dementia is distinct from delirium and depression and other psychiatric disease, and in the elderly may coexist with them

  • Delirium is an acute confusional state that often occurs in response to an identifiable trigger

    • Typically involves fluctuating level of arousal and improves after removal or treatment of the precipitating factor

  • Depression and other psychiatric disease sometimes lead to complaints of impaired cognition (pseudodementia)

    • Symptoms should improve with appropriate psychiatric treatment

    • Evidence suggests that a persistent, untreated mood disorder may predispose to the development of an age-related dementia

    • Psychiatric symptoms can clearly exacerbate cognitive impairment in patients who already have dementia

• Rapidly progressive dementia (eg, Jakob-Creutzfeldt disease) is defined as obvious decline over a few weeks to a few months

Demographics

• Prevalence of Alzheimer dementia in the United States

  • Doubles every 5 years in the older population, reaching 30–50% at age 85

  • Predicted to be 15 million by 2060

• Typically begins after age 60, and the prevalence doubles approximately every 5 years thereafter

• Women suffer disproportionately, as patients (even after age adjustment) and as caregivers

• Alzheimer disease accounts for two-thirds of cases of dementia in the United States, with vascular dementia (either alone or combined with Alzheimer disease) accounting for much of the rest

Symptoms and Signs

• Memory impairment with at least one or more of the following

  • Aphasia (typically, word finding difficulty)

  • Apraxia (inability to perform previously learned tasks)

  • Agnosia (inability to recognize objects)

  • Impaired executive function (poor abstraction, mental flexibility, planning, and judgment)

• Alzheimer disease

  • Typical earliest deficits are in memory and visuospatial abilities

  • Social graces may be retained despite advanced cognitive decline

  • Personality changes and behavioral difficulties (wandering, inappropriate sexual behavior, aggression) may develop as the disease progresses

  • Hallucinations, delusions, and symptoms of depression often occur as dementia worsens

  • End-stage disease characterized by

    • Near-mutism

    • Inability to sit up

    • Inability to hold up the head

    • Inability to track objects with the eyes

    • Difficulty with eating and swallowing

    • Weight loss

    • Bowel or bladder incontinence

    • Recurrent respiratory or urinary infections

• "Subcortical" dementias

  • Psychomotor slowing

  • Reduced attention

  • Early loss of executive function

  • Personality changes

• Lewy body dementia

  • May be confused with delirium, as fluctuating cognitive impairment is frequently observed

  • Rigidity and bradykinesia are primarily noted; tremor is rare

  • Hallucinations—classically visual and bizarre—may occur

• Frontotemporal dementias

  • Personality change (euphoria, disinhibition, apathy) and compulsive behaviors (often peculiar eating habits or hyperorality)

  • In contrast to Alzheimer disease, visuospatial function is relatively preserved

• Dementia with motor findings, such as extrapyramidal features or ataxia, may represent a less common disorder (eg, progressive supranuclear palsy, corticobasal ganglionic degeneration, olivopontocerebellar atrophy)

Differential Diagnosis

• Neurodegenerative disease (see Table 24–6)

• Infection or inflammatory disease

• Neoplasm or a paraneoplastic condition

• Endocrine or metabolic disease

• Drugs or toxins

• Normal pressure hydrocephalus

• For rapidly progressive dementia, also consider

  • Prion disease

  • Infections

  • Toxins

  • Neoplasms

  • Autoimmune and inflammatory diseases, including corticosteroid-responsive (Hashimoto) encephalopathy and antibody-mediated paraneoplastic syndromes

Laboratory Tests

• Initial recommended tests include

  • Complete blood count

  • Thyroid-stimulating hormone (TSH)

  • Vitamin B₁₂ level

  • Electrolytes

  • Creatinine

  • Glucose

  • Calcium

  • Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides

• Further tests that may be informative, but are not considered routine, include:

  • HIV antibody

  • Syphilis testing (eg, rapid plasma reagin [RPR], fluorescent treponemal antibody [FTA] tests)

  • Heavy metal screen

  • Liver tests

  • Lyme serology

  • Paraneoplastic autoimmune antibodies

  • CSF fluid protein and cultures

  • Low serum ceruloplasmin levels or urinary copper excretion

  • ApoE genotyping

Imaging Studies

• Noncontrast CT scanning sufficient in older patients with more classic picture of Alzheimer disease

• MRI scanning without contrast is beneficial for

  • Younger patients

  • Persons who have focal neurologic signs, seizures, gait abnormalities, acute or subacute onset

• Positron-emission tomography (PET)

  • Labeled with fluorodeoxyglucose (FDG)

    • May identify particular brain structures that are hypometabolic and thus likely to harbor pathology

    • May be useful in discriminating between Alzheimer disease and frontotemporal dementia

  • Labeled with ligand for beta-amyloid

    • Is highly sensitive to amyloid pathology

    • May help provide positive evidence for Alzheimer disease in a patient with cognitive decline

    • However, after age 60 or 70, amyloid plaques can accumulate in the absence of cognitive impairment; thus, the specificity of a positive amyloid scan diminishes with age

  • Radiolabeled ligands for tau, a pathogenic protein in Alzheimer disease, progressive supranuclear palsy, and some forms of frontotemporal dementia, has entered clinical trials and may help refine premortem diagnostic accuracy

Diagnostic Procedures

• Evaluate for deficits related to cardiovascular accidents, parkinsonism, or peripheral neuropathy

• The combination of the "clock draw" test (in which the patient is asked to sketch a clock face, with all the numerals placed properly, and the two clock hands positioned at a specified time); and the "three-item recall" at 1 minute test is a fairly quick and good screen; an abnormally drawn clock markedly increases the probability of dementia

• When patients fail either of these screening tests, further testing with the The Montreal Cognitive Assessment (MoCA) questionnaire, neuropsychological testing, or other instruments (eg, Folstein MiniMental State Exam [MMSE]) is warranted

• Examine for comorbid conditions that may aggravate the disability

Nonpharmacologic Approaches

• Provide structure and routine

• Discontinue all nonessential drugs and correct, if possible, sensory deficits

• Exclude unrecognized delirium, pain, urinary obstruction, or fecal impaction

• Caregivers should speak simply to the patient, break down activities into simple component tasks, and use a "distract, not confront" approach

• Aerobic exercise (45 minutes most days of the week) and frequent mental stimulation

  • May reduce the rate of functional decline and decrease the patient's caregiving needs

  • May reduce the risk of dementia in normal individuals

Pharmacologic Approaches

• Anticholinesterase inhibitors (donepezil, galantamine, rivastigmine, memantine) are first-line therapy for Alzheimer disease and dementia with Lewy bodies

  • Modest improvements in cognitive function in mild to moderate dementia

  • May be modestly beneficial in improving neuropsychiatric symptoms

  • Do not appear to prevent progression of disability or institutionalization

  • Starting dosages

    • Donepezil, 5 mg orally daily (maximum 10–23 mg daily)

    • Galantamine, 4 mg orally twice daily (maximum 12 mg twice daily); a once-daily extended-release formulation is also available

    • Rivastigmine, 1.5 mg orally twice daily (maximum 6 mg twice daily) or 4.6, 9.5, or 13.3 mg/24 hours transdermally daily

    • Memantine, 5 mg orally daily (maximum 10 mg twice daily)

  • Increase doses gradually as tolerated

  • Side effects include nausea, diarrhea, anorexia, weight loss, and syncope

• Choose medications based on symptoms—depression, anxiety, psychosis

• Haloperidol

  • May modestly reduce aggression, but not agitation

  • Significant adverse effects including risk of sudden death

• Atypical antipsychotic agents (risperidone, olanzapine, quetiapine, aripiprazole, clozapine, ziprasidone)

  • Better tolerated than older agents

  • However, should be avoided in patients with vascular risk factors due to an increased risk of weight gain, stroke, and sudden death

  • Associated with hyperglycemia in diabetic patients

  • Considerably more expensive than haloperidol

• FDA has issued black box warning about the risk of QTc prolongation and torsades de pointes on ECG with both haloperidol and atypical antipsychotic agents in treatment of depression-related psychosis

• Starting and target neuroleptic dosages are low (eg, haloperidol 0.5–2.0 mg; risperidone 0.25–2 mg)

• Selective serotonin reuptake inhibitors

  • Generally safe and well-tolerated in elderly, cognitively impaired patients

  • May be efficacious for the treatment of depression, anxiety, or agitation

  • Paroxetine should be avoided because it has anticholinergic effects

  • Buproprion or venlafaxine may also be tried

• Insomnia is common

  • Trazodone (25–50 mg orally at bedtime as needed) can be safe and effective

  • Avoid over-the-counter antihistamine hypnotics, along with benzodiazepines, because of their tendency to worsen cognition and precipitate delirium

• The combination of dextromethorphan and quinidine (up to 30/10 mg orally twice daily) has shown promise in early clinical trials

• Vitamin E, 1000 international units twice daily

  • Appears to reduce the rate of functional decline in patients with Alzheimer disease

  • However, it does not affect cognition or prevent the development of Alzheimer disease in patients with mild cognitive impairment

Follow-Up

• Federal regulations require drug reduction efforts at least every 6 months if antipsychotic agents are used in a nursing home patient

• Drivers with dementia are at an increased risk for motor vehicle accidents; however, many patients continue to drive safely well beyond the time of diagnosis

  • There is no clear-cut evidence to suggest a single best approach to determining a patient's risk

  • There is no accepted "gold standard" test of incapability

  • Therefore, clinicians must consider several factors when forming a recommendation about whether a patient should continue driving

• Often early in the course of dementia, patients start having difficulty managing their financial affairs

  • Clinicians should have some proficiency to address financial concerns

  • No gold standard test is available to identify when a patient with dementia no longer has financial capacity

  • However, the clinician should be on the lookout for signs that a patient is either at risk for or actually experiencing financial incapacity

  • Clinicians should be able to educate about the need for advance financial planning and to recommend that patients complete a durable power of attorney for finance matters while the capacity to do so still remains

Complications

• Clinicians should be alert for signs of elder abuse when working with stressed caregivers

Prognosis

• Life expectancy with Alzheimer disease is typically 3–15 years

• Other neurodegenerative dementias, such as Lewy body dementia, show more rapid decline

• Hospice is often appropriate for patients with end-stage dementia

When to Refer

• Referral of all patients with new, unexplained cognitive decline for neuropsychological testing may be helpful to distinguish dementia from depression, to diagnose dementia in persons of poor education or very high premorbid intellect, and to aid diagnosis when impairment is mild

When to Admit

• Dementia complicates other medical problems, and the threshold for admission should be lower

• Dementia alone is not an indication for admission, but admission is sometimes necessary when a superimposed delirium poses safety risks at home