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Practice of Geriatrics
William E. Reichman, M.D., and Jeffrey L. Cummings, M.D.
Relative Frequency of Causes of Dementia
Causes of Dementia
Evaluation of Dementia
Management of Dementia
Dementia is a syndrome of acquired persistent dysfunction in several domains of intellectual function including memory, language, visuospatial ability, and cognition (abstraction, mathematics, judgment, and problem solving). Disturbances of mood and alterations in personality and behavior often accompany the intellectual deterioration. Dementia results from a wide variety of conditions including degenerative, vascular, neoplastic, demyelinating, infectious, inflammatory, toxic, metabolic, and psychiatric disorders (Table 26-1). The onset of dementia may be abrupt (trauma or stroke) but is more often gradual. While the majority of dementing illnesses are progressive, in some cases the course of dementia may be modified by appropriate therapeutic interventions. Despite accurate identification of the cause of dementia and provision of symptomatic treatment, affected patients typically suffer marked and progressive impairment in occupational and social functioning. The economic, social, and psychological cost of dementing illnesses on patients and their families is staggering.


Dementia is a growing public health concern. Although specific figures vary, there is a consensus that the incidence and prevalence of dementia increase with advancing age. In many studies it is reported that dementia affects nearly 5% of the population over age 65. Dementia is most frequent in the fastest growing segment of the population, those over age 75.1 Studies suggest that 3% of the population between the ages of 65 and 74 may have Alzheimer’s disease (AD), the most common cause of dementia. This number increases to nearly 19% of the group aged 75 to 84 years, and among persons aged 85 years and above, the figure may approach 50%.2 It is estimated that nearly 4 million Americans presently suffer from the disorder. The expense of long-term care for afflicted patients over the age of 65 has been estimated at $40 billion annually.1
The anticipated expansion of the number of demented patients in the population and its associated cost raise serious questions for those involved in health care planning. Issues to be resolved include choosing the most cost-effective diagnostic tests for routine evaluation of intellectual deterioration, selecting the most effective therapeutic and management strategies, and planning the most humane and fiscally responsible type of long-term care.
This chapter reviews the clinical features of the major syndromes of dementia and discusses the essential components of an evaluation for dementia. Finally, guidelines for management of the more common behavioral problems and mood alterations encountered in patients with dementia are discussed. Special ethical considerations in the medical and surgical care of demented patients are also reviewed.
A classic study of the underlying neuropathology in dementia was reported in 1970 by Blessed and colleagues.3 The brains of 50 patients who had died in an institution with chronic fatal dementia were examined. Alzheimer’s disease was found in 50%, cerebrovascular disease in 17%, and mixed AD and cerebrovascular disease in 25%. Together, neuropathologic changes consistent with AD and cerebrovascular disease were found in more than 90% of all patients with dementia in this population.
Clinical studies analyzing the frequency of different illnesses in living patients with dementia have used a variety of assessment methodologies, patient selection criteria, and diagnostic approaches. In such studies, AD accounts for 39% to 70% of cases, followed, in decreasing order of frequency, by vascular causes of cognitive impairment (13% to 37%) and depression (1% to 18%). A variety of other conditions have been noted in 26% to 48% of cases. Dementing illnesses that are potentially reversible (including vitamin B12 and folate deficiency, hypothyroidism, depression) have been found in 3% to 29%. Dementias whose course could be modified by appropriate therapeutic interventions, such as vascular disease or Parkinson’s disease, account for 20% to 46% of cases.4,5 and 6
As a group, these studies suggest that a host of disease states can cause or contribute to the development of dementia. In some of these disorders, timely identification and subsequent treatment may alter the course of intellectual decline. Larson and co-workers7 demonstrated that in a group of 200 patients over the age of 60 with suspected dementia, more than 30% had more than one medical condition that contributed to the dementia state. After treatment, 28% experienced cognitive improvement of at least one month’s duration.
Degenerative Dementias
Alzheimer’s disease is the most common cause of dementia in the elderly. The onset of the disease is insidious, generally occurring after the age of 55 and increasing in frequency of occurrence with advancing age. The course is marked by a gradual deterioration of intellectual function, a decline in the ability to accomplish routine activities of daily living, and enduring changes in personality and behavior. Useful guidelines for the clinical diagnosis of Alzheimer’s disease have been established by McKhann and co-workers.8 These criteria require that the patient be between the ages of 40 and 90 years at the time of disease onset, demonstrate progressive loss of memory, and have impairment of at least one additional neuropsychological function. These required deficits must be documented by a standardized mental status examination and neuropsychological assessment. Finally, no additional systemic or brain disorder may be present that could be the cause of the dementia.
The neurobehavioral features of classic dementia of the Alzheimer type include memory impairment, disturbances in language (aphasia), visuospatial deficits, and impaired ability in calculation and abstraction. Disturbances of other cortical functions such as agnosia (impaired recognition) and apraxia (inability to carry out a motor task in the absence of sensory loss, hemiparesis, or difficulty in comprehension) may be observed. The memory impairment characteristic of AD includes deficits in new learning and an inability to recall previously learned material accurately. The language disturbance typical of AD is best characterized as a transcortical sensory aphasia; there is a fluent verbal output accompanied by anomia, impaired comprehension, preserved repetition, and aphasic writing. Although patients may be able to read aloud, their comprehension for written material is impaired.9 Visuospatial impairment is evidenced by environmental disorientation and an inability to draw figures or copy designs.
Alterations in personality are an early and ubiquitous finding in AD. Patients become increasingly passive, are more coarse in their display of emotions, and are less spontaneous. Some of these symptoms may mimic depression, but more often they occur in the absence of a clearly depressed mood or thoughts of worthlessness, hopelessness, or guilt. Depressed mood may be evident at some time during the course of the illness in 40% to 50% of patients. However, the percentage of patients with AD who meet strict diagnostic criteria for major depression is considerably less (10% to 20%).10 In up to half of patients with AD, psychosis with delusions of infidelity, theft, harm, or abandonment is encountered.11 Hallucinations may also occur in patients with AD but are less common than delusions. Hallucinations may be visual and auditory in nature. Other behavioral abnormalities include motor restlessness, agitation, anxiety (inability to separate from the caregiver), catastrophic reactions, aggression, wandering, and insomnia.12
Although patients with AD have striking neuropsychological and behavioral disturbances, their primary motor, somatosensory, and visual functions remain intact throughout most of the disease course. In classic AD, extrapyramidal dysfunction (parkinsonism, tremor, and chorea) is absent, and neurologic abnormalities such as rigidity, myoclonus, ataxia, seizures, and dysarthria do not appear until the late stages.
In the middle stage of AD, electroencephalography (EEG) may show theta-range slowing. Neuroimaging studies such as computed tomography (CT) and magnetic resonance imaging (MRI) are normal or show mild cerebral atrophy. In the later stages of the disease, EEG may show delta-range slowing, and neuroimaging procedures disclose cortical atrophy, sulcal enlargement, and ventricular dilatation. Although they are invariably present, these findings are not specific to AD.
The clinical features of AD reflect the relatively selective involvement of the parietal, medial temporal, frontal convex, and basal forebrain regions found at autopsy. The neuropathologic alterations characteristic of AD include neuronal loss, gliosis, an abundance of neuritic plaques, neurofibrillary tangles, amyloid angiopathy, and granulovacuolar degeneration.13 Neurochemical abnormalities in AD include cholinergic depletion and more variable disturbances of the noradrenergic and serotonergic systems.
Risk factors for AD have been reported to include age, female gender, head trauma, family history of AD, Down’s syndrome, low educational level, and the presence of the apolipoprotein-epsilon 4 (APO-E4) allele on chromosome 19. The extent to which AD is an inherited disease has not yet been fully elucidated. However, several important recent advances have identified three separate chromosomal loci associated with familial AD—the presenillin genes 1 (chromosome 14) and 2 (chromosome 1) and the amyloid precursor protein (APP) gene (chromosome 21). These genes appear to be most frequently associated with early-onset (before age 60) familial AD. In the presence of mutations in these genes, AD appears to be inherited in an autosomal dominant fashion. The APO-E4 allele has been reported to be a significant genetic risk factor for AD. This allele is more common in those with either sporadic or late-onset familial AD. The number of APO-E4 alleles correlates with an earlier age of onset as well as an increased risk of development of the disease.
Pick’s disease and other frontotemporal dementias (FTD) are a heterogeneous group of disorders that share several clinical features with AD such as rate of progression and duration. Many FTD patients are also aphasic and manifest preserved motor integrity. The language disturbance characteristic of Pick’s disease initially includes anomia, but there is a more stereotyped and perseverative verbal output than that found in AD. Unlike AD, in the early stages of FTD, memory, calculation, and visuospatial function are relatively well preserved. The most striking feature of this disorder is an extravagant change in the patient’s personality including disinhibition, impulsivity, inappropriate jocularity, and intrusiveness. In some patients, the behavioral changes consist of prominent passivity or atypical depressive symptoms; there may be elements of the Kluver-Bucy syndrome (hyperorality, dietary changes, compulsive exploratory behaviors, hypersexuality, agnosia, and placidity).14 Motor neuron disease has also been associated with FTD and has a more rapidly progressive course than Pick’s disease. In FTD, EEG may show diffuse or frontal-temporal slowing. CT or MRI frequently reveals focal frontal-temporal atrophy. These features are compatible with the frontal or temporal lobar atrophy found on postmortem examination of the affected brain. Neuronal degeneration is the characteristic neuropathologic change of FTD. Argyrophilic neuronal inclusions (Pick bodies) with or without balloon cells are also seen in Pick’s disease.15
Diagnostically, single-photon emission computed tomography (SPECT) may help to distinguish FTD from AD. SPECT demonstrates selective reductions in cerebral perfusion of the anterior hemispheric regions in FTD. In AD, cerebral blood flow is preferentially diminished in the posterior cerebral regions.16
The clinical features of AD and FTD (aphasia, amnesia, apraxia, agnosia) reflect the predominantly cortical involvement in these disorders. Another group of degenerative disorders that cause dementia involves predominantly the subcortical structures (basal ganglia, thalamus, cerebellum, and rostral brain stem). The major disorders in this category include Parkinson’s disease, Wilson’s disease, progressive supranuclear palsy, Huntington’s disease, Fahr’s disease (idiopathic basal ganglia calcification), multisystem atrophies, and thalamic dementia. Approximately 40% of patients with Parkinson’s disease have overt dementia and up to 70% have more subtle neuropsychological deficits. The neuropsychological features of subcortical disorders include disturbances in attention and concentration, poor motivation, impaired information-processing speed, and memory disturbances. Patients appear depressed and apathetic, and their psychomotor responses are slow. On memory testing, they have retrieval failures but improve with cues. This memory deficit is often accompanied by disturbances of executive functions including problem solving and strategy formulation.17 Unlike patients with AD and FTD, patients with subcortical dementia syndromes have prominent movement disorders. Depending on the specific disease state, patients may present with a hypokinetic, rigid parkinsonian state or a hyperkinetic, choreic, dystonic, or ataxic disturbance (Table 26-2).


Lewy body dementia (LBD) is characterized by a pathologic accumulation of Lewy bodies in the brain stem and cortex. The clinical syndrome consists of marked fluctuations in cognition, visual and auditory hallucinations, clouding of consciousness, and mild spontaneous extrapyramidal symptoms. In some patients severe extrapyramidal signs may first emerge after exposure to standard doses of neuroleptic agents.18,19 Unlike delirium, with which it shares some common clinical features, LBD persists and becomes progressively worse. Pathologically, LBD is characterized by numerous neuritic plaques, rare neurofibrillary tangles, and Lewy bodies in cortical and brain stem neurons. Several authors have argued that LBD may be more common than has been historically reported and in fact may be second to AD as a cause of dementia in the elderly.
Vascular Dementias
Dementia resulting from ischemic cerebral injury, or vascular dementia, is second in frequency to AD as a cause of chronic progressive intellectual decline. The percentage of all cases of dementia due to cerebrovascular disease has been quoted as ranging from 12% to 20%.20 The neuropsychological deficits seen in patients with vascular dementia result from ischemic damage to multiple areas within the cortex and subcortical structures. The clinical features of vascular dementia are determined by the number, site, and volume of infarctions. There is often a temporal relationship between the onset of cognitive loss and the emergence of neurologic signs or symptoms of stroke. Historical features typically include an abrupt onset of deficits, stepwise progression of deficits, and fluctuation in the severity of symptoms. Relative preservation of personality with emotional lability, depression, somatic preoccupation, and nocturnal confusion are often noted. Patients typically show evidence of associated atherosclerosis (electrocardiographic changes, history of myocardial infarction or angina, retinopathy), history of hypertension, and focal neurologic signs and symptoms. Gait ataxia, parkinsonism, and urinary incontinence are not infrequent. A history of stroke or transient ischemic events further supports the diagnosis of multi-infarct or vascular dementia. The Ischemia Scale (IS)21 is a checklist of the clinical features of multi-infarct dementia including its onset, course, and neurologic and psychiatric findings. A score of 7 or above for a given patient is considered compatible with a vascular origin of the patient’s dementia. Despite a sensitivity and specificity of 70% to 80% in separating vascular dementia from Alzheimer’s disease,22 the IS is less well equipped to diagnose reliably the comorbid occurrence of these two disorders in the same patient. There is evidence that this scale may overdiagnose vascular dementia in patients who are subsequently found to have AD.23
Several different clinical presentations of vascular dementia are possible depending on the predominant site of neuroanatomic involvement. Vascular dementia may be a consequence of multiple cortical infarctions, multiple subcortical infarctions (lacunar state), ischemic injury to the deep hemispheric white matter (Binswanger’s disease), or a combination of these. Major depression and psychosis frequently occur in dementia due to cerebrovascular disease.11 In vascular dementia, CT scans may demonstrate multiple areas of lucency compatible with infarction. MRI is particularly sensitive in that it shows increased signal intensity in areas of ischemic injury. EEG may show multifocal slowing.
Dementia resulting from stroke is most often associated with fibrinoid necrosis of arterioles resulting from sustained hypertension. Other causes of vascular dementia include diabetes mellitus, cardiac embolization, and inflammatory vasculitides.
Metabolic and Toxic Dementias
Elderly patients may suffer from several systemic illnesses that predispose them to the development of chronic metabolic encephalopathies. In the majority of cases, metabolic or toxic disturbances of the central nervous system produce transient effects on cognition (delirium). However, when these effects persist for an extended period of time, dementia is diagnosed. These chronic confusional states accompany a wide variety of systemic disorders, including severe anemia, disturbances of the thyroid, parathyroid, and adrenal axes, cardiac and pulmonary insufficiency, renal and hepatic disease, and vitamin deficiencies (particularly deficiencies of vitamins B12 and niacin).
Toxic causes of dementia are of particular concern in the elderly because the aged consume disproportionately large amounts of over-the-counter and prescribed medications. The alterations in drug metabolism, distribution, binding, and excretion that accompany normal aging increase the risks of drug toxicity. In addition, with advanced age, the brain may be more sensitive to the effects of drugs even in the absence of excessive dosing or polypharmacy.24 Agents that are especially likely to cause chronic confusional states include tranquilizers, sedative-hypnotics, and centrally acting antihypertensive agents. Long-term alcoholism and chronic use of other drugs also cause dementia. Likewise, chronic exposure to industrial solvents and heavy metals may cause dementia accompanied by peripheral neuropathy.
Salient clinical features of the metabolic and toxic dementias include fluctuating arousal, inattention, and impaired memory and orientation. Severe disturbances of language and of higher cortical functions such as agnosia or apraxia are notably uncommon. Motor system disturbances such as myoclonus, tremor, and asterixis are frequently present, and EEG demonstrates diffuse slow-wave activity. With resolution of the responsible metabolic derangement or cessation of exposure to the offending toxin, improvement of neuropsychological deficits usually occurs.
Myelin Diseases with Dementia
In the elderly, diseases affecting the white matter are decidedly less common than those affecting the cortical and subcortical gray matter. However, there are several myelinoclastic disorders that may cause dementia in the elderly. Secondary white matter diseases include Binswanger’s disease and viral illnesses such as acquired immune deficiency syndrome (AIDS) dementia complex, and progressive multifocal leukoencephalopathy. Multiple sclerosis is the most common demyelinating disorder, although it rarely begins after the fourth decade of life. The course is relapsing and remitting and involves an accumulation of enduring neurologic deficits. Classic symptoms include optic neuritis, myelopathy with spasticity and incontinence, cerebellar dysfunction, and internuclear ophthalmoplegia. Intellectual decline accompanies these features in nearly 50% of afflicted patients.25 Psychiatric symptoms often noted are depression and mania. Rarer white matter dementing diseases include metachromatic leukodystrophy, adrenoleukodystrophy, cerebrotendinous xanthomatosis, membranous lipodystrophy, adult Schilder’s disease, Marchiafava-Bignami’s disease, and hereditary adult-onset leukodystrophy.26
Normal Pressure Hydrocephalus
Hydrocephalic dementia is characterized clinically by the triad of dementia, ataxia, and urinary incontinence. The dementia is typified by psychomotor slowing, bradyphrenia, inattention, impaired memory, apathy, and concreteness. Symptoms usually evolve over a period of several months to years. In normal pressure hydrocephalus (NPH), cerebrospinal fluid (CSF) obstruction occurs at the level of the arachnoid granulations responsible for absorption into the venous circulation. This state, associated with normal intracranial pressure, results from trauma, subarachnoid hemorrhage, encephalitis, or meningitis. In some cases it may be idiopathic. CT or MRI confirms the presence of increased ventricular size in hydrocephalus. The pattern of CSF flow is studied by radionuclide cisternography and CSF pressure monitoring.9 Despite its frequent consideration in the differential diagnosis, NPH is a rare cause of dementia. The triad of dementia, incontinence, and ataxia is more often a sign of vascular dementia than of NPH.
Hydrocephalus with increased intracranial pressure is seen in patients with brain tumors (see next section, Neoplastic Dementias) or inflammatory conditions such as ependymitis or arachnoiditis. Symptoms of increased intracranial pressure include headache, papilledema, nausea, emesis, and lethargy. Somnolence or coma may eventually result.
Neoplastic Dementias
Neoplasms that either arise from the brain or metastasize from extracranial tumors may cause dementia through direct compression, hydrocephalus, infiltration of brain tissue, or increased intracranial pressure. Generally, clinical symptoms arising from intracranial tumors are insidious in onset and gradually progressive. Over a period of several weeks to months, patients may experience lethargy, headache, depression, impaired concentration, and memory disturbance. Focal neurologic symptoms may emerge; gait ataxia and incontinence are sometimes noted. While some tumors such as a subfrontal meningioma can cause dementia without other neurologic features, this is the exception rather than the rule.
Meningeal carcinomatosis, another cause of neoplastic dementia, results from neoplastic invasion of the meninges. It is associated with neoplasms of the breast, lung, gastrointestinal tract, and malignant melanoma. Patients experience increased intracranial pressure, cranial nerve palsies, and a chronic confusional state characterized by disturbed attention and concentration.
Occult systemic neoplasms such as oat cell carcinoma of the lung and carcinomas of the ovary or breast have been associated with dementia as a remote effect. Depression and anxiety have also been noted in the clinical presentation. Patients with this type of paraneoplastic syndrome often have clinical evidence of cerebellar dysfunction, or cerebellar atrophy is noted on neuroimaging studies. Seizures, myeloradiculopathy, and myopathy have also been described in patients with this condition.
Traumatic Dementias
Trauma to the brain often results in alterations in personality and enduring intellectual deficits such as aphasia, amnesia, apraxia, and concreteness. The inferior frontal lobes and medial temporal lobes are particularly susceptible to damage in closed head injury. Such trauma may cause hemorrhage, laceration, contusion, and shearing injuries of the neuronal axons. In the elderly, the formation of subdural hematomas is of special concern. Affected patients may develop a chronic confusional state with fluctuating attention and transient, minor focal neurologic signs. Dementia pugilistica has been noted in older or retired boxers following repeated blows to the head. The dementia is accompanied by ataxia and extrapyramidal dysfunction.
Infection-Related Dementias
Several different types of infections of the nervous system can produce dementia. Bacterial infection usually causes an acute encephalopathy (delirium) rather than a chronic confusional state or dementia. General paresis (neurosyphilis) is a chronic spirochetal infection characterized by dementia with prominent frontal lobe signs. Neuroborreliosis (central nervous system Lyme disease) is another cause of dementia that may or may not have been preceded by the classic “target-like” lesion and erythema migrans. Whipple’s disease is a poorly understood bacterial infection characterized by meningeal signs, dementia, supranuclear gaze palsy, and systemic symptoms (lymphadenopathy, malaise, diarrhea, fever, arthralgia). Diagnosis depends on a jejunal biopsy demonstrating the characteristic macrophages.
Chronic meningitis resulting from fungal, protozoan, or helminthic infection can cause a chronic confusional state with increased intracranial pressure and cranial nerve abnormalities.
Acute viral infections such as herpes encephalitis can cause a persistent postencephalitic dementia if the injury to the central nervous system (CNS) is severe. Viruses can also cause dementia through a slowly progressive encephalitis. Slow viral dementias include AIDS dementia complex, subacute sclerosing panencephalitis, and progressive multifocal leukoencephalopathy. AIDS dementia complex results from direct infection of the brain by the human immunodeficiency virus (HIV). Clinically, affected patients present with apathy, depression, psychomotor slowing, forgetfulness, and dilapidated cognition.27 Headache is a common associated feature. Neurologic symptoms such as motor signs and unusual movements may be noted. Opportunistic infections of the CNS (toxoplasmosis, cryptococcosis, and tuberculosis) occur in patients with AIDS and may also cause or exacerbate dementia.
Jakob-Creutzfeldt disease is a potentially transmissible disorder that begins in the fifth to seventh decades. It has been linked to an infectious membranous protein called a prion. The course is rapidly progressive and leads to death within several months. Patients manifest a progressive dementia, myoclonus, and pyramidal and extrapyramidal signs. During the course of the illness, EEG shows periodic spike discharges with background slowing in the majority of patients. Progressive multifocal leukoencephalopathy results from papovavirus CNS infection in immunocompromised patients. The virus produces the greatest impact on the cerebral white matter.
Inflammatory Dementias
Systemic autoimmune disorders such as systemic lupus erythematosus, sarcoidosis, and temporal arteritis may result in dementia through vascular occlusion and direct inflammatory and immunologic effects on the brain parenchyma. Diagnosis depends on an elevated sedimentation rate and confirmatory serologic abnormalities.
Psychiatric Disorders with Dementia
One of the more common causes of intellectual decline in the elderly has been historically called depressive “pseudodementia” but is now referred to as the dementia syndrome of depression (DOD). The syndrome includes forgetfulness, psychomotor retardation, poor motivation, and cognitive slowing. Patients have evidence of depressed mood and may have a personal or family history of depression. Following treatment of the depression, neuropsychological improvement is noted. Dementia has been identified occasionally in patients with other psychiatric disturbances such as acute mania and schizophrenia.28
Comprehensive evaluation of acquired intellectual impairment and associated behavioral and mood disturbances has several purposes: (1) to establish the cause for dementia, (2) to guide appropriate treatment, (3) to identify reversible or treatable concurrent medical illnesses, (4) to determine prognosis, (5) to facilitate education and counseling of family members, (6) to provide genetic advice when appropriate, and (7) to identify pertinent psychosocial stressors and family concerns that directly affect caregiving. To best accomplish these goals, a thorough assessment, consisting of a careful medical and psychiatric history, physical, neurologic, and mental status examinations, laboratory evaluation, and, often, neuroimaging procedures, is mandatory (Table 26-3). The mini-mental state examination29 provides a brief method of recording and following the changes in mental state of the patient with dementia (Table 26-4).



No battery of laboratory tests is completely applicable to all demented patients. Individualized investigations are dictated by the particular constellation of signs and symptoms presented. However, in all patients with dementia certain initial studies should be done. Routine tests of greatest diagnostic use include a complete blood count, serum electrolytes (including calcium, serum glucose, creatinine, blood urea nitrogen, bilirubin, and alkaline phosphatase), syphilis serology, vitamin B12 level, and thyroid function tests (especially thyroid-stimulating hormone). If pertinent risk factors are identified and the clinical state is compatible with AIDS dementia, antibody testing may be indicated. In the presence of the appropriate clinical history, serologic tests for Lyme disease may be warranted. Lumbar puncture may be appropriate if a demyelinating disorder is suspected, the dementia syndrome is atypical, or evidence of infection or inflammation of the CNS (headache, meningeal signs, fever, seizures) is present.
A neuroimaging study such as MRI or CT scanning of the head is a necessary component of most evaluations for dementia. MRI offers more accurate structural and pathologic assessment but is more time consuming and costly to perform. It cannot be used in patients who have a pacemaker or metallic intracranial objects such as surgical clips. Whichever study is selected, MRI or CT adds to diagnostic precision by detecting stroke, mass lesions, areas of demyelination, hydrocephalus, or atrophy. The routine applicability of newer modalities such as SPECT or position emission tomography (PET) awaits further confirmation. However, SPECT may be useful in helping to distinguish FTD from AD. EEG is helpful diagnostically when infections, Jakob-Creutzfeldt disease, inflammatory disorders, or toxic-metabolic causes of dementia are under consideration. Additionally, EEG is needed for the evaluation of seizure activity. In the evaluation of AD, routine clinical use of serum APO-E4 testing or CSF analysis of tau protein or beta amyloid is discouraged until additional data regarding the sensitivity and specificity of these tests emerge.
The role of cerebral biopsy in the evaluation of dementia is restricted. This procedure rarely leads to the diagnosis of a reversible condition and often results in substantial morbidity.30 Cerebral biopsy is most often justified in the evaluation of Jakob-Creutzfeldt disease when special precautions may be needed to limit transmission during postmortem study.31
The neuropsychological deficits, neuropsychiatric symptoms, and medical illnesses that afflict demented patients pose significant clinical challenges for physicians and caregivers. Effective treatment and management involve both pharmacologic and nonpharmacologic interventions.
Restoration of Intellectual Function
At the present time, no single pharmacologic agent has shown clear efficacy in reversing or halting the intellectual deterioration accompanying the two most common dementia syndromes, AD and vascular dementia. In patients with AD, however, the cholinesterase inhibitors tacrine and donepezil have produced clinical benefit in approximately 30% to 50% of treated patients. When evident, the clinical response to these drugs is approximately the amount of cognitive decline that would otherwise have been noted after 6 to 12 months of disease progression. Tacrine may produce liver function abnormalities and requires serum studies when the dose is increased; donepezil has no associated liver function abnormalities. Both agents may cause gastrointestinal distress. In vascular dementia, optimal control of hypertension and hyperlipidemia and cessation of smoking help to prevent recurrent stroke; many clinicians advocate the use of one daily enteric-coated aspirin to further diminish the risk.
For the other nondegenerative dementing disorders, improvement in cognitive function following therapy is rarely complete. Replacement of vitamin B12, ventricular shunting for patients with NPH, or correction of hypothyroidism often leads to symptomatic improvement but rarely to complete recovery. Importantly, these interventions can halt disease progression and are thus of considerable benefit.
Several nonpharmacologic techniques can aid caregivers and physicians in helping the demented patient remain as functional as possible throughout the course of the illness. These include (1) maintaining eye contact and speaking to the patient in a simple, distinct, and calm manner, (2) asking only one question at a time and allowing ample time for a response, (3) establishing a regular, structured daily routine while encouraging the patient’s active participation, (4) calmly reorienting the patient when necessary, (5) breaking down all tasks into several simple steps, and (6) setting realistic expectations for what the patient can and cannot do.
Management of Neuropsychiatric Symptoms
In contrast to the largely unsuccessful experience in arresting or reversing the intellectual deficits of AD and vascular dementia, many of the psychiatric and behavioral disturbances commonly encountered in these patients are directly amenable to nonpharmacologic and pharmacologic intervention (see also Chapter 25).
Nonpharmacologic interventions for severe anxiety and psychosis include gentle reassurance and distraction. It is rarely helpful to attempt to convince patients that their beliefs are false or that they are hallucinating. Such confrontation by the caregiver or physician can escalate any concomitant agitation.
Occasionally, demented patients may become agitated or aggressive. If the patient is physically violent, caregivers should remove any potentially dangerous objects and ensure their own safety. If distraction or reassurance does not improve the patient’s behavior, medication may be the only available option.
For the treatment of psychosis, neuroleptics are the agents of choice. Although there are few double-blind placebo-controlled trials that compare the efficacy of different classes of agents, neuroleptics such as haloperidol, thiothixene, and thioridazine are commonly used with moderate benefit. Unfortunately, in many patients the use of these drugs is complicated by increased confusion and other side effects. Older patients may be particularly susceptible to the tendency of higher potency neuroleptics (haloperidol, thiothixene, fluphenazine) to cause extrapyramidal reactions such as bradykinesia, rigidity, tremor, and restlessness. Use of lower potency agents (thioridazine, chlorpromazine) may result in orthostatic hypotension, sedation, and anticholinergic side effects (dry mouth, constipation, urinary retention, blurred vision, and tachycardia). As a result, and despite the increased risk of extrapyramidal side effects, higher potency agents such as haloperidol and thiothixene in low doses (0.5 to 2 mg po qd) have generally been the drugs of first choice to treat psychoses. Recently, atypical neuroleptic medications such as risperidone have been used to treat such symptoms. This medication causes less extrapyramidal dysfunction but may be associated with hypotension. In patients who are particularly sensitive to the extrapyramidal effects of neuroleptic medications (e.g., those who have Lewy body dementia), clozapine may be efficacious and better tolerated. However, the risk of agranulocytosis associated with the use of this drug warrants weekly determinations of white blood cell counts.
If neuroleptic-induced extrapyramidal signs appear, lowering the dosage and treating the patient with amantadine 100 mg po bid or tid is often effective. Chronic use of neuroleptics may lead to tardive dyskinesia or one of its variants, such as tardive dystonia or tardive akathisia (restlessness).
In patients with mild anxiety or restlessness, moderately short acting benzodiazepines such as oxazepam 10 to 15 mg po qd or bid, or lorazepam 0.5 to 1 mg po qd or bid may be useful. Buspirone (15 to 45 mg po qd) also may be of benefit.
The pharmacologic management of nonpsychotic agitation or combativeness may include use of neuroleptics, benzodiazepines (for minor agitation or anxiety), or agents such as anticonvulsants, beta-adrenergic blockers, and serotonin-enhancing agents. Although no particular neuroleptic is especially superior in controlling aggression, a more sedating agent such as thioridazine in starting doses of 10 to 25 mg po bid may be preferred. The dose can be increased carefully, watching for the emergence of orthostasis and anticholinergic side effects.
If an aggressive or agitated patient fails to respond to either low- or high-potency neuroleptics or if significant side effects develop that preclude continuation of a chosen agent, alternative classes of psychotropic drugs may be employed. Carbamazepine in doses of 400 to 1200 mg po qd may have some use in treating aggressive, agitated behavior. Valproic acid in a dose range of 250 to 1000 mg po qd has also been proved effective for these symptoms. Monitoring of serum levels of these drugs and complete blood counts and liver function tests are required in these patients. Other agents that may be helpful include serotonin-enhancing drugs such as trazodone 50 to 400 mg po qd or clonazepam 0.5 to 4 mg po qd in divided doses. Buspirone 15 mg po bid or fluoxetine 20 to 40 mg po qd may also serve as alternatives. Finally, some authors have advocated the use of propranolol to control aggressive, violent behavior. The dose ranges vary considerably (60 to 1500 mg po qd in divided doses); in older patients, doses in the lowest ranges are most safely employed. Contra-indications include sinus bradycardia, congestive heart failure, and asthma.32 Cholinergic agents may decrease psychosis or agitation in some patients.
Pharmacologic management of depression and other mood disturbances in patients with dementia is similar to that employed in the nondemented elderly patient. Initially, physical contributors to the alteration in mood state should be investigated such as co-existing medical illnesses and drug or medication toxicity. Patients’ feelings about their loss of intellectual ability, associated social and financial problems, and guilt about increased caregiver burden must be thoroughly explored and addressed. While these factors are being dealt with, pharmacologic treatment can be directed to target symptoms such as dysphoric mood and disturbances of sleep, appetite, and energy. Treatment with antidepressant agents that have few anticholinergic side effects such as bupropion, sertraline, fluoxetine, paroxetine, venlafaxine, trazodone, and nefazodone may afford some relief without producing additional confusion. Pharmacotherapy should be commenced with the lowest possible dose, and upward titration should be performed judiciously.
Patients with dementia frequently have sleep disturbances. They may be restless or wander aimlessly in the night. Initial interventions should be directed toward improving sleep hygiene. Tactics include (1) avoiding caffeinated beverages and medications with stimulant effects in the afternoon or evening, (2) limiting eating or watching television in bed, encouraging only sleeping, (3) discouraging excessive intake of fluids in the evening to prevent nocturia, (4) investigating other medical causes of insomnia such as pain, cardiac or pulmonary disease, or restless legs syndrome, and (5) discouraging daytime naps. When these interventions are not sufficient to restore adequate sleep, pharmacotherapy is indicated. Although no particular hypnotic agent has demonstrated truly superior efficacy in patients with dementia, chloral hydrate 500 to 1000 mg po hs is often of benefit. Trazodone 50 to 150 mg po hs is frequently used for this purpose as well. Short-acting benzodiazepines such as oxazepam (10 to 30 mg po hs) or lorazepam (0.5 to 2 mg po hs) may be helpful if given 1 hour before bedtime. If these agents are used for prolonged periods, however, patients may experience early morning awakening. Long-acting benzodiazepines such as flurazepam and diazepam are best avoided because their metabolites often accumulate, leading to daytime drowsiness or increased confusion. A sedating neuroleptic such as thioridazine (25 to 50 mg po hs) may be beneficial in treating nocturnal agitation.
Caregiver Issues
Ongoing surveillance and treatment of caregiver stress and depression is of paramount importance in the successful management of the demented patient. Identification and participation of other potential caregivers should be encouraged. When feasible, primary caregivers should be encouraged to attend caregiver support groups while lessening their own burden of responsibility through the use of ancillary assistance such as daycare, respite services, or home health aides. Referral of caregivers to organizations such as the Alzheimer’s Association is often helpful (1-800-272-3900). Early in the course of dementia, referral should be made for financial and legal counseling. Additionally, caregivers should be educated about the signs and symptoms of potentially complicating medical problems such as urinary tract infection and incontinence. Simple strategies such as beginning a regular toileting schedule, using adult diapers, and monitoring fluid intake can aid in the successful management of urinary incontinence. Over time, information should also be gathered about the family’s attitudes toward nursing home admission, and appropriate advice about this issue should be given as needed.

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