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in the clinic
Dementia
Prevention page ITC4-2
Screening page ITC4-3
Diagnosis page ITC4-4
Treatment page ITC4-7
Practice Improvement page ITC4-13
CME Questions page ITC4-16
Section EditorChristine Laine, MD, MPHDavid Goldmann, MD
Physician WriterDavid M. Blass, MDPeter V. Rabins, MD, MPH
The content ofIn the Clinic is drawn from the clinical information and
education resources of the American College of Physicians (ACP), including
PIER (Physicians Information and Education Resource) and MKSAP (Medical
Knowledge and Self-Assessment Program). Annals of Internal Medicine
editors develop In the Clinic from these primary sources in collaboration with
the ACPs Medical Education and Publishing Division and with the assistance
of science writers and physician writers. Editorial consultants from PIER and
MKSAP provide expert review of the content. Readers who are interested in these
primary resources for more detail can consult http://pier.acponline.org and other
resources referenced in each issue ofIn the Clinic.
The information contained herein should never be used as a substitute for clinical
judgment.
2008 American College of Physicians
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What medical interventions orhealth behaviors can help patientsprevent dementia?Although there are several risk fac-tors for different types of dementia,data supporting the effectiveness
of specific preventive measures arelimited.
Hypertension
Untreated hypertension in mid-lifeand later is a proven risk factor forboth Alzheimer disease and vascu-lar dementia (3). A number of ran-domized, controlled trials (RCTs)have shown that treating hyperten-sion reduces the risk for dementia.
A large, placebo-controlled RCT with 2418
participants demonstrated that treating
systolic hypertension in patients over the
age of 60 years reduced the incidence of
dementia by 50%, from 7.7 cases to 3.8
cases per 1000 patient-years (4).
Another placebo-controlled RCT with 6106
participants showed that treating hyper-
tension with the angiotensin-converting
enzyme inhibitor perindopril with or with-
out the thiazide diuretic indapamide
reduced the incidence of recurrent stroke
with dementia by 34% and of recurrent
stroke with any cognitive decline by 45% inpatients with past stroke or transient
ischemic attack (5).
Hypercholesterolemia and
Diabetes Mellitus
Hypercholesterolemia, particularlyin mid-life, is associated with anincreased incidence of bothAlzheimer disease and vascular
dementia, (6), and casecontrolstudies have shown an associationbetween use of cholesterol-loweringmedications and reduced incidenceof dementia (7). Diabetes has been
shown in both longitudinal cohortand casecontrol studies to be anindependent risk factor for vasculardementia (8, 9). However, as withhypercholesterolemia, there are notrials that demonstrate that treatingdiabetes prevents dementia.
Lifestyle Modifications
Cigarette smoking is associatedwith an increased risk for stroke,although the evidence for an asso-
ciation with Alzheimer disease ismixed (10). Head injury earlier inlife has been shown in a number ofepidemiologic studies to be associ-ated with dementia later in life(11). Finally, physical inactivity,both in mid-life and later, has beenassociated with an increased risk fordementia in both retrospective andprospective studies (12, 13). Thus,counseling patients to quit smok-ing; engage in behaviors to reducethe risk for head injury, such aswearing seat belts and bike hel-mets; and be physically active mayreduce the risk for dementia.
Medications
Clinicians should regularly reviewthe medication regimens of eld-erly patients and minimize use of
2008 American College of Physicians ITC4-2 In the Clinic Annals of Internal Medicine 1 April 2008
Dementia is defined as a decline in cognitive function from baseline.
It is a syndrome caused by a variety of disorders, the most common
of which are Alzheimer disease, vascular dementia, Lewy body
dementia, and frontotemporal dementia. The incidence and prevalence of
dementia increase with age. It is estimated that by the year 2047, more than
9 million Americans will have some form of it (1). Institutionalization is ulti-
mately required for many patients with dementia, and 67% die in nursing
homes (2). Although there is currently no cure for most forms of dementia,
research findings and accumulated clinical experience support a set of prac-tices that serve to maximize the function and overall well-being of patients
with dementia and their caregivers.
Prevention
1. Brookmeyer R, Gray S,Kawas C. Projectionsof Alzheimers dis-ease in the UnitedStates and the publichealth impact ofdelaying diseaseonset. Am J PublicHealth. 1998;88:1337-42. [PMID: 9736873]
2. Mitchell SL, Teno JM,
Miller SC, et al. Anational study of thelocation of death forolder persons withdementia. J Am Geri-atr Soc. 2005;53:299-305. [PMID:15673356]
3. Launer LJ, Ross GW,Petrovitch H, et al.Midlife blood pres-sure and dementia:the Honolulu-Asiaaging study. Neuro-biol Aging. 2000;21:49-55. [PMID:10794848]
4. Forette F, Seux ML,Staessen JA, et al.Prevention ofdementia in ran-domised double-blind placebo-con-trolled SystolicHypertension inEurope (Syst-Eur) trial.Lancet. 1998;352:1347-51. [PMID:9802273]
5. PROGRESS Collabora-tive Group. Effects ofblood pressure low-ering with perindo-pril and indapamidetherapy on dementiaand cognitive declinein patients with cere-brovascular disease.Arch Intern Med.
2003;163:1069-75.[PMID: 12742805]6. Notkola IL, Sulkava R,
Pekkanen J, et al.Serum total choles-terol, apolipoproteinE epsilon 4 allele, andAlzheimers disease.Neuroepidemiology.1998;17:14-20.[PMID: 9549720]
7. Jick H, Zornberg GL,Jick SS, et al. Statinsand the risk ofdementia. Lancet.2000;356:1627-31.[PMID: 11089820]
8. Curb JD, RodriguezBL, Abbott RD, et al.Longitudinal associa-
tion of vascular andAlzheimers demen-tias, diabetes, andglucose tolerance.Neurology. 1999;52:971-5. [PMID:10102414]
9. Meyer JS, McClinticKL, Rogers RL, et al.Aetiological consid-erations and risk fac-tors for multi-infarctdementia. J NeurolNeurosurg Psychia-try. 1988;51:1489-97.[PMID: 3221215]
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10. Lee PN. Smokingand Alzheimers dis-ease: a review of theepidemiological evi-dence. Neuroepide-miology. 1994;13:131-44. [PMID:8090255]
11. Mortimer JA, vanDuijn CM, Chandra
V, et al. Head traumaas a risk factor forAlzheimers disease:a collaborative re-analysis of case-control studies.EURODEM Risk Fac-tors Research Group.Int J Epidemiol.1991;20 Suppl 2:S28-35. [PMID: 1833351]
12. Broe GA, HendersonAS, Creasey H, et al.A case-control studyof Alzheimers dis-ease in Australia.Neurology. 1990;40:1698-707. [PMID:2146525]
13. Yoshitake T, Kiy-
ohara Y, Kato I, et al.Incidence and riskfactors of vasculardementia andAlzheimers diseasein a defined elderlyJapanese popula-tion: the HisayamaStudy. Neurology.1995;45:1161-8.[PMID: 7783883]
14. Larson EB, KukullWA, Buchner D, et al.Adverse drug reac-tions associated withglobal cognitiveimpairment in eld-erly persons. AnnIntern Med. 1987;107:169-73. [PMID:
2886086]15. Etminan M, Gill S,
Samii A. Effect ofnon-steroidal anti-inflammatory drugson risk ofAlzheimers disease:systematic reviewand meta-analysis ofobservational stud-ies. BMJ. 2003;327:128. [PMID:12869452]
16. ADAPT ResearchGroup. Cardiovascu-lar and cerebrovas-cular events in therandomized, con-trolled AlzheimersDisease Anti-
Inflammatory Pre-vention Trial(ADAPT). PLoS Clin
Trials. 2006;1: e33.[PMID: 17111043]
17. Cache County Mem-ory Study Investiga-tors. Hormonereplacement therapyand incidence ofAlzheimer disease inolder women: theCache County Study.JAMA. 2002;288:2123-9. [PMID:12413371]
2008 American College of PhysiciansITC4-3In the ClinicAnnals of Internal Medicine1 April 2008
Prevention... Although there are few data to support specific measures to prevent
dementia, clinicians should treat cardiovascular risk factors, such as hypertension,hypercholesterolemia, and diabetes, and encourage smoking cessation and regular
exercise. They should also counsel patients about avoiding head injury and avoid
prescribing medications that can alter cognitive function. Neither NSAIDs nor
estrogen should be recommended for prevention of dementia.
CLINICAL BOTTOM LINE
medications that can cause cogni-tive impairment, such as benzodi-azepines, anticholinergics, barbitu-rates, and other sedative-hypnotics.A number of studies have shownthat elderly patients taking benzo-diazepines or other sedative-hypnotics perform more poorly oncognitive tests than those not tak-
ing these medications (14).Because inflammation is present inthe brains of patients withAlzheimer disease and epidemio-logic evidence links use of non-steroidal anti-inflammatory drugs(NSAIDs) earlier in life to a lowerrisk for Alzheimer disease (15),some have questioned whether
NSAIDs might prevent dementia.However, prospective studies todate have not shown a protectiveeffect of NSAIDs, and they are notrecommended for prevention ofdementia (16).
Significant epidemiologic evidencelinks mid-life estrogen use to a
lower incidence of dementia later inlife (17). However, in prospectiveprevention trials, including thelarge Womens Health InitiativeMemory Study, use of estrogen plusprogestin for prevention of demen-tia was associated with an increasedincidence of dementia, as well asother medical complications (18).
Screening
Should clinicians screen for
dementia?The U.S. Preventive Services TaskForce concluded that there is insuf-ficient evidence to recommend foror against widespread screening fordementia in elderly patients (19).However, many patients withdementia in the primary care set-ting, even those in more advancedstages of the disease, remain undi-agnosed despite having routinegeneral medical care (20).
Moreover, patients referred todementia specialists after screeninghave been diagnosed at an earlierstage of illness than those referredfrom physicians or families (21).Therefore, given the high preva-lence of dementia and its associatedmorbidity, the clinician shouldconsider secondary case-finding
measures for dementia in elderly
patients with unexplained func-tional decline, deterioration inhygiene, questionable adherence tomedication regimens, or new-onsetpsychiatric symptoms.
What methods should cliniciansuse when looking for dementia?When looking for dementia in eld-erly patients, clinicians should use astandardized screening instrumenttogether with a brief history from
the patient and a knowledgeableinformant. The screening instru-ment should be easy to use, demon-strate high sensitivity, be widelyavailable, and be supported by nor-mative population data relevant tothe patient. Two examples of suchinstruments are the Mini-MentalStatus Examination (22) and theMini-Cog (23).
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18. WHIMS Investiga-tors. Estrogen plusprogestin and theincidence of demen-tia and mild cogni-tive impairment inpostmenopausalwomen: theWomens Health Ini-tiative MemoryStudy: a randomizedcontrolled trial.JAMA. 2003;289:2651-62. [PMID:12771112]
19. U.S. Preventive Ser-vices Task Force.Screening fordementia and otherdiseases. Guide toclinical preventiveservices. 2nd ed. Bal-timore: Williams &Wilkins; 1996: 531-40. Accessed atwww.guideline.gov/summary/summary.aspx?doc_id=3690on 7 February 2008.
20. Valcour VG, MasakiKH, Curb JD, et al.
The detection ofdementia in the pri-mary care setting.Arch Intern Med.2000;160:2964-8.[PMID: 11041904]
2008 American College of Physicians ITC4-4 In the Clinic Annals of Internal Medicine 1 April 2008
What elements of the history aremost important in evaluatingpatients with suspected dementia?Clinicians should use the patientshistory to characterize the cognitivedeficits, generate a differential diag-nosis, and attempt to determine thecause of the dementia. This is bestaccomplished by identifying med-
ical, neurologic, and psychiatricsymptoms that may be clues to thecause of the cognitive problems anddetailing their order of appearance,severity, and associated features. Inthe case of cognitive difficulties, itis mandatory to try to obtaincollateral information from aknowledgeable informant, becausecognitive dysfunction can impairthe patients ability to serve as anaccurate reporter. It is often easierto collect this information, as wellas information about psychiatricsymptoms, without the patientpresent.
In taking the history, it is criticalfor clinicians to be knowledgeableabout the differential diagnosis andnatural history of the most com-mon types of dementia (Table 1).For example, in classic Alzheimerdisease, early symptoms are domi-nated by difficulties with short-
term memory, subtle language andvisuospatial perception difficulties,and changes in executive functionwith significant reductions in effi-ciency and organizational abilitiesof which the patient may or maynot be aware. Symptoms begininsidiously and are slowly progres-sive. Overall level of alertnessremains unimpaired. Patients or
families may not label these diffi-culties as memory problems per sebut may instead report multiplerepetitions of questions or conver-sations with no recollection of pre-vious discussions, increased forget-fulness manifested by losing objectsor becoming confused while shop-ping, or simply overall increased
disorganization and decreased effi-ciency. Symptoms are often firstnoticed or reported at the time of alife change, such as the death of aspouse or a move into a new resi-dence. See the Box for clinicaldiagnostic criteria for definite andprobable Alzheimer disease (24).
Many elderly patients report minorcognitive problems, such as mildforgetfulness, difficulty remember-
ing names, and mildly reducedconcentration. In patients withoutdementia, these symptoms are typi-cally sporadic, do not worsen sig-nificantly over time, are easilycompensated for, and do not affectfunction. In contrast, in earlydementia, the symptoms insidiouslybecome established as a pattern,worsen over time, are difficult tocompensate for, and eventually
affect speech fluency and hamperthe performance of routine activi-ties, such as meal preparation, billpaying, and financial planning.Patients with memory problemsshould be screened for dementia asdescribed previously, but a completedementia evaluation should bereserved for those with the clinicalsyndrome of dementia.
Diagnosis
Screening... There is insufficient evidence to recommend for or against screeningasymptomatic people for dementia. However, clinicians should be alert for unex-
plained functional decline, deterioration in hygiene, questionable adherence to
medication regimens, or new-onset psychiatric symptoms in elderly patients and
use standardized instruments, such as the Mini-Mental Status Examination or the
Mini-Cog, to look for cognitive dysfunction in such patients.
CLINICAL BOTTOM LINE
Clinical Diagnosis ofAlzheimer Disease (AD)
Definite AD: Clinical criteria for probable AD
plus histopathology confirmation
Probable AD: Dementia by clinical examination
and standardized instrument(e.g., Mini-Mental State
Examination) Deficits in >2 areas of cognition
Progressive cognitive decline
Normal levels of consciousness
Onset between age 40 and 90years
No other cause
Supportive factors, includingpositive family history, cerebralatrophy on neuroimagining,normal electroencephalogramand lumbar puncture
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2008 American College of PhysiciansITC4-5In the ClinicAnnals of Internal Medicine1 April 2008
Table 1. Differential Diagnosis of Cognitive Difficulties*
Disease Characteristics Notes
Alzheimer Early symptoms include gradual memory loss, preserved The presenting problem to the physician may not relate todisease level of consciousness, impaired IADL performance, subtle cognition. Earliest presenting symptoms may be paranoid
language errors, and worsened visualspatial perception. delusions or depression, which are only later appreciated asMiddle-stage symptoms include apraxia, disorientation, part of a dementia. Dementia may initially become manifestand impaired judgment. As the illness progresses, aphasia, with a major life change. Neurologic signs, such as falls, tremor,apraxia, agnosia, inattention, and leftright confusion weakness, or reflex abnormalities, are not typical early in thedevelop. In the final stages patients are dependent for disease. Seizures occur frequently in advanced disease; theirIADL care, and lose the ability to ambulate and even swallow presence earlier suggests a diagnosis other than Alzheimer
disease.
Vascular Ideally, loss of function should be correlated temporally with Should be suspected in any patient with cerebrovascular riskdementia cerebrovascular events. Stepwise deterioration may be seen. factors, even if a neurologic examination does not suggest aLevel of consciousness should be normal. May be present in stroke.patients with silent strokes, multiple small strokes, orsevere diffuse cerebrovascular disease.
Lewy body Mild parkinsonism; unexplained falls; hallucinations May account for up to 20% of total dementia cases. Should bedementia and delusions early in the illness; extreme sensitivity to suspected in patients with nonvascular dementia but abnormal
extrapyramidal side effects of antipsychotic medications; neurologic examination.gait difficulties and falls; and fluctuating cognition.
Frontotemporal Onset often before age 60 years. Language difficulties Includes such disorders as progressive supranuclear palsy,dementia are common. Memory often preserved early on. Prominent primary progressive aphasia, semantic dementia, amyotrophic
personality changes, often with behavioral disturbances, lateral sclerosis with dementia, and corticobasal degeneration.such as hyperphagia, worsened impulsivity or aggression, or Functional neuroimaging often demonstrates diminishedprominent apathy. function in frontal or temporal lobes.
Delirium Altered and fluctuating level of alertness and attention, Must be excluded in order to diagnose dementia. Diagnosis isoften with globally impaired cognition. May have abrupt critical because delirium may reflect serious systemic disturbance,
onset. Patients may have psychomotor retardation and such as metabolic abnormalities, medication effects, or infection.mental status abnormalities of depressed or elevatedmood, hallucinations, delusions, and agitated behavior.
Major Low mood; anhedonia; diminished sense of self-worth; Cognitive impairment may result solely from major depression.depression hopelessness; altered appetite, libido, and sleep; increased Major depression may also be the initial presentation of dementia.
somatic complaints; irritability; and wishes for death.
Medications Common offenders include benzodiazepines, barbiturates, Cognitive impairment of patients with dementia may beanticholinergics, and other sedative-hypnotics. exacerbated by medications.
Mild cognitive Evidence of memory impairment in the absence of other Many progress to dementia at a rate of about 12%15%impairment cognitive deficits or functional decline. per year.
Subdural May or may not occur in setting of falls or head injury. Classic presentation is the exception rather than the rule.hematoma Nonspecific headache. Level of consciousness may wax Neurologic deficits may be minor.
and wane.
Traumatic Clinical features may vary according to site of injury. The postconcussion syndrome may include inattention.brain injury Personality and mood changes are common.
Normal- Dementia, gait abnormality (slow, broad-based, If suspicion is high, lumbar puncture with pre- and post-tappressure impaired turning), and urinary incontinence. Dementia gait monitoring is performed. Ventriculoperitoneal shuntinghydrocephalus is often associated with psychomotor slowing and apathy. can be curative in some patients.
Brain tumor Frontal or corpus callosum tumors result in memory Neuroimaging rules the diagnosis in or out.(primary or impairment with global intellectual decline. Parietalmetastatic) lobe tumors may produce apraxia, aphasia, agnosia,
agraphesthesia, astereognosia, and neglect.
Vitamin B12 Insidious onset. May be associated with depression. Neuro- If serum B12 is in the low-normal range, elevated serumdeficiency logic examination may reveal diminished proprioception methylmalonic acid and homocysteine levels indicate low
and vibratory sense, ataxia, and positive Babinski sign. intracellular vitamin B12. Anemia may be absent.
Thyroid Both hypo- and hyperthyroidism can lead to cognitive Thyroid-stimulating hormone should be checked at thedisease difficulties. beginning of the dementia work-up.
Chronic Chronic alcohol use appears to lead to a mild-to-moderate This is distinct from the Korsakoff syndrome, an isolated loss ofalcohol use dementia, which may reverse after a period of abstinence. short-term memory without global dementia.
Toxins Aromatic hydrocarbons, solvents, heavy metals, Urine or serum toxicology and heavy metal screens are useful.
marijuana, opiates, and sedative-hypnotics.Parkinson Features of subcortical dementia, cortical dementia, or both. In contrast to Lewy body dementia, patients with Parkinsondisease Free recall may be impaired with preservation of recognition disease and dementia typically have motor symptoms of
memory. May have impaired visualspatial function. Parkinson disease long before dementia, and do not haveprominent psychotic symptoms or fluctuating consciousness.
Other causes Multiple sclerosis, CNS vasculitis, neurosarcoidosis, systemiclupus erythematosus, advanced liver or renal disease, Wilsondisease, chronic CNS infection, electrolyte abnormalities,neurosyphilis, HIV-associated dementia, Huntington disease,and CreutzfeldtJacob disease.
*CNS = central nervous system; IADL = instrumental activities of daily living.
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How can clinicians distinguishdementia from delirium?Clinicians evaluating a patient witha change in cognition or overallfunction must consider delirium.Delirium is global impairmentof cognition with characteristicworsening of alertness and atten-tion. Onset may be abrupt or grad-ual, often with notable fluctuationsin the level of impairment.Although some patients may beagitated and manifest psychoticsymptoms, others are slowed,drowsy, and appear mildlydepressed or withdrawn. Promptdiagnosis of delirium is critical,because it usually reflects an under-lying systemic condition, such asinfection, metabolic derangement,medication effect, or malignancy.
How should clinicians evaluatepatients with suspected dementia?Clinicians should use the generalphysical examination to look forsigns of conditions that can causeor worsen cognitive decline (Table1). A complete mental status exam-ination begins with an evaluation ofalertness, general appearance, andcooperation. Speech should beevaluated both for its content(grammatical or semantic errors)
and form (rate, fluency, volume).The patients mood and affectshould be assessed for evidence ofdepression, anxiety or mania, andsuicidality, and thought content andperception are examined for thepresence of delusions or hallucina-tions, as well as obsessions orcompulsions.
The cognitive examination shouldinclude a standard instrument, suchas the MMSE, which can be per-
formed in about 5 minutes andprovides an overview of orientation,immediate recall, concentration,naming, language function, praxis,and visualspatial perception. TheMMSE should be augmented bytesting delayed recall by asking thepatient to repeat 3 words from theMMSE 20 to 30 minutes aftertheir initial presentation. Naming
and praxis can be further tested byasking the patient to name a seriesof common and uncommon objectsand by asking them to demonstratetasks, such as brushing hair or teethor slicing bread. Abstract reasoningand judgment should be tested byasking for solutions to real-lifeproblems, such as what to do if onesmells smoke in the house, or forinterpretation of proverbs or simi-les. Drawing a clock (sponta-neously, or copying from an alreadydrawn figure in the event of diffi-culty) is a quick test of visualspatialperception, praxis, and planningability. Corticosensory deficits, suchas neglect or leftright confusion,can be quickly tested for as well.
What laboratory tests are helpfulin the evaluation of patients with
cognitive dysfunction?According to guidelines from theAmerican Psychiatric Associationand American Academy of Neurol-ogy, patients who are being evalu-ated for cognitive problems shouldhave a laboratory evaluation forcommon medical disorders, withselected additional studies depend-ing on the specific clinical situation(see Box on opposite page).
In general, patients with cognitivedifficulties less than 3 years induration should undergo a neuro-imaging study (computed tomo-graphy [CT] or magnetic resonanceimaging [MRI] scanning of thehead) to exclude cerebrovasculardisease, hemorrhage, tumor, orhydrocephalus as the cause of thecognitive dysfunction. Studies showthat, in patients with cognitiveproblems, neuroimaging detectssignificant cerebrovascular disease
even in patients in whom it was notsuspected clinically (25). The yieldis higher in patients with early ageof onset, rapid progression, focalneurologic deficits, cerebrovasculardisease risk factors, recent falls,central nervous system (CNS)infection, unexplained fluctuatinglevel of consciousness, or symptomsatypical of Alzheimer disease. The
21. Barker WW, Luis C,Harwood D, et al.
The effect of a mem-ory screening pro-gram on the earlydiagnosis ofAlzheimer disease.Alzheimer Dis AssocDisord. 2005;19:1-7.[PMID: 15764864]
22. Folstein MF, FolsteinSE, McHugh PR.Mini-mental state.A practical methodfor grading the cog-nitive state ofpatients for the clini-cian. J Psychiatr Res.1975;12:189-98.[PMID: 1202204]
23. Borson S, Scanlan J,Brush M, et al. Themini-cog: a cogni-tive vital signsmeasure for demen-tia screening inmulti-lingual elderly.Int J Geriatr Psychia-try. 2000;15:1021-7.[PMID: 11113982]
24. McKhann G, Drach-man D, Folstein M,et al. Clinical diagno-sis of Alzheimersdisease: report ofthe NINCDS-ADRDAWork Group underthe auspices ofDepartment ofHealth and HumanServices Task Forceon Alzheimers Dis-ease. Neurology.1984;34:939-44.[PMID: 6610841]
2008 American College of Physicians ITC4-6 In the Clinic Annals of Internal Medicine 1 April 2008
Elements of the CognitiveExamination
Standardized instrument (e.g.,Mini-Mental State Examination)
Object naming
Task demonstration
Word recall
Proverb or situation interpretation
Clock drawing or figure copying
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routine use of single-photon emis-sion CT (SPECT) or positronemission tomography (PET) scan-ning is not recommended, althoughthese tests may be useful in specificinstances, such as in differentiatingAlzheimer disease from frontotem-poral dementia (26).
Genetic studies are not routinely
indicated in the evaluation ofdementia unless there is a specificconcern about Huntington disease.There is evidence that testing fortheApoE4allele does not add sub-stantially to the diagnosis (27).Testing for 1 of the 3 autosomaldominant gene mutations found inpatients with familial Alzheimerdisease is occasionally pursuedwhen multiple family membersare affected.
Other tests should be reserved forspecific situations. Electroen-cephalography may be useful whenthere is a question of delirium,seizures, or encephalitis. Lumbarpuncture may be indicated inpatients under age 55 years and inthose with rapidly progressivedementia, a positive rapid plasma
reagin, suspicion of acute orchronic CNS infection or malig-nancy, or immunosuppression.Neuropsychological testing pro-vides the most comprehensiveassessment of cognitive functionand is particularly useful when thediagnosis of dementia is unclear orit is necessary to precisely charac-terize the patients cognitiveimpairment.
25. Massoud F, Devi G,Moroney JT, et al.
The role of routinelaboratory studiesand neuroimagingin the diagnosis ofdementia: a clinico-pathological study. JAm Geriatr Soc.2000;48:1204-10.[PMID: 11037005]
26. Foster NL, Heide-brink JL, Clark CM, etal. FDG-PETimproves accuracyin distinguishingfrontotemporal
dementia andAlzheimers disease.Brain. 2007;130:2616-35. [PMID:17704526]
27. van der Cammen TJ,Croes EA, DermautB, et al. Genetic test-ing has no place as aroutine diagnostictest in sporadic andfamilial cases ofAlzheimers disease.J Am Geriatr Soc.2004;52:2110-3.[PMID: 15571552]
2008 American College of PhysiciansITC4-7In the ClinicAnnals of Internal Medicine1 April 2008
Diagnosis... Clinicians should evaluate patients who present with cognitive andfunctional decline with a detailed history of medical, neurologic, and psychiatric
symptoms from the patient and a knowledgeable informant and with a thorough
physical, mental status, and cognitive examination. Basic laboratory studies
include a comprehensive metabolic panel, complete blood count, thyroid-stimulating
hormone level, and vitamin B12
level. Selected patients may require additional
laboratory tests. Clinicians should consider CT or MRI scanning of the head in
patients with cognitive difficulties with a duration less than 3 years and in those
with early age of onset, rapid progression, focal neurologic deficits, cerebrovascular
disease risk factors, or atypical symptoms.
CLINICAL BOTTOM LINE
TreatmentWhat should clinicians advisepatients (and their caregivers)about their general health andhygiene?Even in the early stages of demen-tia, patients may have difficultycomprehending the details of their
medical care requirements; organiz-ing their care; and keeping track ofappointments, medications, orother recommendations. The clini-cian should be alert to these limita-tions and help prepare a care planthat compensates for them. Later inthe illness, patients may be unableto identify physical signals, such asconstipation, dysuria, tooth pain, or
diminished visual or auditory acu-ity, and the clinician should proac-tively look for these problems.
It is important to attend to generalmedical and preventive care as con-scientiously as in patients without
dementia. A major stroke or heartattack due to uncontrolled hyper-tension is likely to impair apatients function and quality of lifeas much as the dementia itself, atleast in the early and middle stagesof the disease. For patients withmore advanced dementia, ongoingattention to nutritional needs, skincare (particularly perineal), toileting
Laboratory Studies for PatientsBeing Evaluated for CognitiveProblems
Comprehensive metabolic profile
Complete blood count
Thyroid-stimulating hormone level
Vitamin B12
level
Rapid plasma reagin orfluorescent treponemal antibody
Selected patients may need toundergo additional tests, including:
HIV
Toxicology screen
Erythrocyte sedimentation rate
Heavy metal screen
Folate
Chest X-ray
Urinalysis
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schedules, and dental and denturecare become more important.
What should clinicians adviseabout safety issues and otheractivities that may requiresupervision?All patients with progressivedementia ultimately lose the abilityto drive, but predicting when it is
unsafe for an individual patient tocontinue to drive is difficult.Nonetheless, it is imperative toaddress the issue, as numerousstudies have demonstrated thatdriving ability becomes impaired inearly stages of the disease.
In a prospective, casecontrol study using
the Washington University Road Test (with
off-road and on-road components), 19%
of patients with very mild Alzheimer dis-
ease failed the test, 41% with mild
Alzheimer disease failed, and only 3% of
controls failed (P < 0.001). Driving experi-
ence did not protect against this deteriora-
tion (28).
The clinician should inquire aboutrecent motor vehicle accidents, nearmisses, or changes in the patientsdriving ability. These inquiriesshould be made in a setting thatfacilitates an open exchange ofinformation and may necessitate
meeting with an informant withoutthe patient present. Patients withearly dementia who have deterio-rating driving skills should beinstructed to stop driving immedi-ately. Patients with early dementiawithout any history of drivingproblems should undergo a drivingevaluation through the local MotorVehicle Administration (MVA) oran occupational therapy program ata local hospital. These evaluationsshould be repeated every 6 monthsto promptly detect deterioration.
State laws differ in regard toreporting patients with a diagnosisof dementia to local MVAs, andthe clinician should be familiarwith the applicable regulations. Theoverall approach to assessment ofdriving in patients with dementia is
outlined in detail in the AmericanAcademy of Neurology Evidence-Based Practice Parameter (29).
Clinicians should assess othersafety issues with the patient andfamily on an ongoing basis. Med-ication administration, cooking, useof power tools and lawnmowers,and handling of firearms eventually
become unsafe for all patients toperform independently. Occupa-tional therapy home-safety assess-ments can be useful in determiningwhich activities can be performedsafely and which need to be limitedor supervised. An activity can oftenbe modified to allow ongoing par-ticipation in a safe fashion, such ascooking or gardening together witha family member or friend. Wan-dering away from home, a fairly
common occurrence, presents sig-nificant safety concerns and mustbe addressed regularly.
What should clinicians adviseabout nonpharmacologicapproaches to sleep problems,behavioral problems, andpsychiatric manifestationsof dementia?Psychiatric symptoms, such asdepression, anxiety, sleep problems,
agitation, hallucinations, and delu-sions are common in patients withdementia and often require inter-vention (30). When symptoms aremild or do not pose immediatedanger, nonpharmacologic manage-ment may be sufficient. Suchapproaches emphasize that manyemotional and behavioral distur-bances can be decoded or under-stood in terms of internal or envi-ronmental triggers. Clinicians andcaregivers should consider the timeof day, location, antecedent factors,people present or absent, proximityto eating or other activities, and theconsequences of the behavior. Ifpatterns are noted, targeted inter-ventions can be developed, imple-mented, and refined. Approachingbehavioral disturbances this waycan often forestall the use of
28. Hunt LA, Murphy CF,Carr D, et al. Reliabil-ity of the Washing-ton University Road
Test. A performance-based assessment
for drivers withdementia of theAlzheimer type. ArchNeurol. 1997;54:707-12. [PMID: 9193205]
29. Dubinsky RM, SteinAC, Lyons K. Practiceparameter: risk ofdriving andAlzheimers disease(an evidence-basedreview): report ofthe quality standardssubcommittee ofthe American Acad-emy of Neurology.Neurology. 2000;54:2205-11. [PMID:10881240]
30. Lyketsos CG, Stein-
berg M, Tschanz JT,et al. Mental andbehavioral distur-bances in dementia:findings from theCache County Studyon Memory inAging. Am J Psychia-try. 2000;157:708-14.[PMID: 10784462]
31. Qaseem A, Snow V,Cross JT Jr, et al. Cur-rent Pharmacologic
Treatment ofDementia: A ClinicalPractice Guidelinefrom the AmericanAcademy of FamilyPhysicians and theAmerican College of
Physicians. AnnIntern Med.2008;148:370-8.
32. Raina P, SantaguidaP, Ismaila A, et al.Effectiveness ofCholinesteraseInhibitors andMemantine for
Treating Dementia:Evidence Review fora Clinical PracticeGuideline. AnnIntern Med.2008;148:379-97.
2008 American College of Physicians ITC4-8 In the Clinic Annals of Internal Medicine 1 April 2008
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psychotropic medications or physi-cal restraints.
When should clinicians prescribeacetylcholinesterase inhibitors andmemantine to slow cognitivedecline?Clinicians should consider prescrib-ing acetylcholinesterase inhibitors,such as donepezil, galantamine, orrivastigmine, to delay cognitivedecline in patients with mild,moderate, or advanced Alzheimerdisease. These drugs are better tol-erated if they are slowly titrated toreach the target dose. The appro-priate duration of treatment has notbeen defined. Although there areno placebo-controlled trials beyond2 years, and most trials only last 6months, clinicians often continuethese medications for much longer
when they feel the patient is bene-fiting from them. When the benefitis unclear, clinicians can considerstopping the drug and resuming it
if an acute cognitive deteriorationoccurs.The neuropeptide-modifyingagent memantine is approved foruse in moderate-to-advancedAlzheimer disease and can be usedin conjunction with acetyl-cholinesterase inhibitors. Table 2lists specific recommendations fortheir use. Tacrine has more side
effects and is no longerrecommended.
Patients and families should beeducated about realistic expecta-tions from these agents. All ofthem have shown statistically sig-nificant improvement in scores onstandardized tests in patients withdementia in clinical trials as well asimprovement on global assessment,but the benefits have been modestand difficult to extrapolate to the
clinical practice setting. Side effectsof anticholinesterase inhibitorsinclude dizziness, nausea, vomiting,and diarrhea and anorexia.
2008 American College of PhysiciansITC4-9In the ClinicAnnals of Internal Medicine1 April 2008
Table 2. Pharmacologic Therapy for Dementia*
Agent Mechanism of Action Dosage Benefits Side Effects Notes
Donepezil Acetylcholin- Begin 5 mg/d. Delayed symptom Nausea, vomiting, Routine liver functionesterase inhibition If tolerated, increase progression in mild, diarrhea, anorexia testing is unnecessary. The
to target dose of moderate, and higher end of the dosing10 mg/day after advanced Alzheimer range may be harder for1 month. disease patients to tolerate.
Galantamine Acetylcholin- Start 4 mg twice daily. Delayed symptom Nausea, vomiting, Routine liver functionesterase inhibition Target dose 24 mg total progression in mild, diarrhea, anorexia testing is unnecessary. The
per day. Increase by 4 mg moderate, and higher end of the dosingtwice daily every 1 month advanced Alzheimer range may be harder foruntil in target range. disease patients to tolerate.
Begin extended-release Improvement in(once daily) galantamine at caregiver-rated8 mg/d. Increase by 8 mg/d quality of lifeevery 1 month to the target was observed.
dose of 24 mg/d.
Rivastigmine Acetylcholin- Start 1.5 mg twice daily. Delayed symptom Nausea, vomiting, Routine liver functionesterase inhibition Target range is 6 to 12 progression in mild, diarrhea, anorexia testing is unnecessary. The
mg/d. Increase by 1.5 mg moderate, and higher end of the dosingtwice daily every 1 month advanced Alzheimer range may be harder foruntil in target range. disease patients to tolerate.
Also available in atransdermal patch.
Memantine NMDA-receptor Begin 5 mg/d. Increase Less functional Dizziness, Available in tablets orantagonism by 5 mg/d every 1 month decline, improved confusion, solution. Avoid
until reaching target of cognition, and headache, concomitant use with10 mg twice daily. reduced demands on constipation amantadine.
caregivers inmoderate-to-advancedAlzheimer disease
* NMDA = N-methyl-D-aspartic acid.
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Memantine can cause dizziness,confusion, headache, and constipa-tion. Neither class of agent shouldbe used in patients with uncon-trolled asthma, closed-angle glau-coma, the sick sinus syndrome, orleft bundle-branch block.TheAmerican College of Physicians hasissued new guidelines on pharma-cologic treatment of dementia, rec-ommending that clinicians base thedecision to initiate therapy withthese agents on individualizedassessment and choose amongthem on the basis of tolerability,side effect profile, ease of use, andcost (31).
A systematic review of 59 studies ofcholinesterase inhibitors and memantinefound that all agents had consistent butmodest effects on cognition and globalassessment. Behavior and quality of lifewere assessed less frequently and showedless-consistent effects. The duration ofmost studies averaged only 6 months, andthere were only 3 head-to-head compara-tive trials (32).
Which other pharmacologicagents may be helpful in treatingless-common types of dementia?The acetylcholinesterase inhibitorrivastigmine has been shown to beeffective in improving cognitiveperformance in patients with mild-to-moderate Parkinson disease indoses similar to those used inAlzheimer disease, and it isbelieved that this benefit will beseen with the other acetyl-cholinesterase inhibitors (33). Anumber of trials have also demon-strated the benefits of acetyl-cholinesterase inhibitor treatmentfor cognition in dementia withLewy bodies (34, 35).
Which pharmacologic agents areineffective in treating dementiaand should be avoided?Vitamin E is no longer recom-mended for routine use inAlzheimer disease, because its useis associated with a possibileincrease in mortality and becauseof a lack of adequate evidence of
efficacy (36, 37). The effectivenessof the herbal supplement Ginkgobilobais not supported by sufficientdata to recommend its general usein patients with dementia (38).Similarly, NSAIDs, estrogen, andergoid mesylates should not beprescribed for the treatment ofcognitive decline.
When should clinicians prescribeantidepressants in patients withdementia?Clinicians should consider prescrib-ing antidepressants in patients withdementia who have coexistingdepression. Major depression ishighly prevalent among patientswith dementia, with nearly onethird of patients developing anepisode of major depression follow-ing the onset of dementia (39).Certain symptoms of major depres-sion may overlap with those ofdementia, such as weight loss anddisturbed sleep, and this sometimescomplicates the diagnosis (40).
A number of RCTs have estab-lished the efficacy of antidepressantmedications in the treatment ofmajor depression in patients with
dementia (4143), although therehave been a number of negativeclinical trials as well. In general, theselective serotonin reuptakeinhibitors are better tolerated thantricyclic agents, but tricyclic agentsmay be used in select patients.These agents may cause mild gas-trointestinal upset at the start oftreatment or when doses arechanged and increase risk for falls,agitation, delirium, or parkinson-
ism. Tricyclic agents can also causeorthostatic hypotension, drymouth, sedation, urinary retention,and constipation and can worsennarrow-angle glaucoma. Medica-tions with greater anticholinergicproperties, such as amitriptyline,should generally be avoided.
33. Emre M, Aarsland D,Albanese A, et al.Rivastigmine fordementia associatedwith Parkinsons dis-ease. N Engl J Med.2004; 351:2509-18.[PMID: 15590953]
34. McKeith I, Del Ser T,Spano P, et al. Effi-cacy of rivastigminein dementia withLewy bodies: a ran-domised, double-blind, placebo-con-trolled internationalstudy. Lancet. 2000;356:2031-6. [PMID:11145488]
35. Beversdorf DQ,Warner JL, Davis RA,et al. Donepezil inthe treatment ofdementia with lewybodies [Letter]. Am JGeriatr Psychiatry.2004;12:542-4.[PMID: 15353396]
36. Sano M, Ernesto C,Thomas RG, et al. Acontrolled trial of
selegiline, alpha-tocopherol, or bothas treatment forAlzheimers disease.
The Alzheimers Dis-ease CooperativeStudy. N Engl J Med.1997;336: 1216-22.[PMID: 9110909]
37. Miller ER III, Pastor-Barriuso R, Dalal D,Riemersma RA,Appel LJ, Guallar E.Meta-analysis: high-dosage vitamin Esupplementationmay increase all-cause mortality. AnnIntern Med. 2005;142:37-46.
[PMID: 15537682]38. Schneider LS,
DeKosky ST, FarlowMR, et al. A random-ized, double-blind,placebo-controlledtrial of two doses ofGinkgo bilobaextract in dementiaof the Alzheimerstype. Curr AlzheimerRes. 2005;2:541-51.[PMID: 16375657]
39. Zubenko GS,Zubenko WN,McPherson S, et al. Acollaborative studyof the emergenceand clinical featuresof the major depres-
sive syndrome ofAlzheimers disease.Am J Psychiatry.2003;160:857-66.[PMID: 12727688]
40. Olin JT, SchneiderLS, Katz IR, et al. Pro-visional diagnosticcriteria for depres-sion of Alzheimerdisease. Am J GeriatrPsychiatry. 2002;10:125-8. [PMID:11925273]
2008 American College of Physicians ITC4-10 In the Clinic Annals of Internal Medicine 1 April 2008
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41. Lyketsos CG, Del-Campo L, SteinbergM, et al. Treatingdepression inAlzheimer disease:efficacy and safety ofsertraline therapy,and the benefits ofdepression reduc-tion: the DIADS.Arch Gen Psychiatry.2003;60:737-46.[PMID: 12860778]
42. Nyth AL, GottfriesCG, Lyby K, et al. Acontrolled multicen-
ter clinical study ofcitalopram andplacebo in elderlydepressed patientswith and withoutconcomitantdementia. Acta Psy-chiatr Scand.1992;86:138-45.[PMID: 1529737]
43. Petracca GM,Chemerinski E, Stark-stein SE. A double-blind, placebo-con-trolled study offluoxetine indepressed patientswith Alzheimers dis-ease. Int Psychogeri-atr. 2001;13:233-40.
[PMID: 11495397]44. Gill SS, Bronskill SE,
Normand SL, et al.Antipsychotic druguse and mortality inolder adults withdementia. AnnIntern Med.2007;146:775-86.[PMID: 17548409]
45. Schneider LS, Dager-man KS, Insel P. Riskof death with atypi-cal antipsychoticdrug treatment fordementia: meta-analysis of random-ized placebo-con-trolled trials. JAMA.2005;294:1934-43.
[PMID: 16234500]46. Schneider LS, Dager-
man K, Insel PS. Effi-cacy and adverseeffects of atypicalantipsychotics fordementia: meta-analysis of random-ized, placebo-con-trolled trials. Am JGeriatr Psychiatry.2006;14:191-210.[PMID: 16505124]
47. Wang PS,Schneeweiss S,Avorn J, et al. Risk ofdeath in elderlyusers of conven-tional vs. atypicalantipsychotic med-
ications. N Engl JMed. 2005;353:2335-41. [PMID: 16319382]
48. Shaw SH, Curson H,Coquelin JP. A dou-ble-blind, compara-tive study of zolpi-dem and placebo inthe treatment ofinsomnia in elderlypsychiatric in-patients. J Int MedRes. 1992;20:150-61.[PMID: 1521671]
2008 American College of PhysiciansIn the ClinicAnnals of Internal Medicine1 April 2008
When should clinicians considerprescribing antipsychotic agentsto treat behavioral disturbances orpsychotic symptoms?Psychotic symptoms, such as hallu-cinations, delusions, and agitatedbehavior, that are mild or infre-quent can often be managed withsupportive care. However, whensymptoms cause significant distressor danger to the patient or others,pharmacotherapy is indicated.Second-generation antipsychoticagents are usually recommendedbecause of a lower risk for tardivedyskinesia than first-generationagents, such as haloperidol, butfirst-generation agents may be usedas well in certain patients. Overall,the efficacy of these agents ismodest. Although the efficacy ofrisperidone and olanzapine is best
supported in the literature, quetiap-ine and aripiprazole are often used.They should be prescribed at thelowest possible dose and for theshortest possible time once pre-scribed; use should be regularlymonitored. They should not beused routinely as sleep agents alone,because of side effects, whichinclude sedation, orthostatichypotension, delirium, ataxia, drymouth, urinary retention, constipa-
tion, and stroke. First-generationagents are more likely to cause tar-dive dyskinesia and neurolepticmalignant syndrome.
In a meta-analysis of all RCTs of second-generation antipsychotics for behavioral
disturbance in patients with dementia,there was a relative risk of 1.54 (95% CI,
1.06 to 2.23) for mortality compared withplacebo- treated patients (45).
In reports released by the manufacturers,
rates of cerebrovascular events were 4% forrisperidone-treated patients (comparedwith 2% for placebo-treated), 1.3% for
olanzapine (0.4% for placebo), and 1.3%for aripiprazole (0.6% for placebo). There
was no evidence of increased risk for strokewith quetiapine use (44).
Evidence of increased mortality andcardiovascular events in patients
ITC4-11
treated with second-generationantipsychotics prompted the U.S.Food and Drug Administration toplace a black-box warning on thelabel of these agents (4447).Treatment with antipsychotic med-ications is also associated with themetabolic syndrome, as well asweight gain, hyperlipidemia, anddiabetes mellitus. Clinicians mustweigh the risks and benefits of theseagents when prescribing them.
Which drugs should clinicians useto treat sleep problems in patientswith dementia?Clinicians should try nonpharma-cologic methods to treat sleepproblems before using medicationsin patients with insomnia becauseof the potential risks associatedwith sedative-hypnotic use in this
population. Careful attentionshould be paid to sleep environ-ment, caffeine consumption, day-time sleeping, afternoon andevening medications, and otherelements of basic sleep hygiene. Ifnecessary, trazodone 25 to 50 mg,zolpidem 5 to 10 mg, or a similaragent can be used cautiously (48).
What other steps should clinicianstake to maximize quality of life inpatients with dementia?Clinicians should proactivelyaddress issues that have the poten-tial to significantly affect quality oflife. Examples include attending tothe working order of sensory aides,such as glasses and hearing aides, toensure proper function; dental care;levels of noise, lighting, and tem-perature; presence of sufficientsocial and cognitive stimuli; cleanli-ness; pain levels; and constipation.
When should clinicians consult aneurologist or psychiatrist andother professionals in patientswith dementia?Clinicians should consider con-sulting a geriatric psychiatrist,neurologist, geriatrician, ordementia specialist regarding thediagnosis of dementia in patients
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49. Chan DC, Kasper JD,Black BS, et al. Pres-ence of behavioraland psychologicalsymptoms predictsnursing home place-ment in community-dwelling elders withcognitive impair-ment in univariatebut not multivariateanalysis. J GerontolA Biol Sci Med Sci.2003;58:548-54.[PMID: 12807927]
50. Yaffe K, Fox P, New-comer R, et al.Patient and care-giver characteristicsand nursing homeplacement inpatients withdementia. JAMA.2002;287:2090-7.[PMID: 11966383]
51. Mittelman MS, FerrisSH, Shulman E, et al.A family interventionto delay nursinghome placement ofpatients withAlzheimer disease. Arandomized con-trolled trial. JAMA.1996;276:1725-31.[PMID: 8940320]
52. Teri L, Logsdon RG,Uomoto J, et al.Behavioral treatmentof depression indementia patients: acontrolled clinicaltrial. J Gerontol BPsychol Sci Soc Sci.1997;52:P159-66.[PMID: 9224439]
53. Haupt M, Karger A,Jnner M. Improve-ment of agitationand anxiety indemented patientsafter psychoeduca-tive group interven-tion with their care-givers. Int J GeriatrPsychiatry. 2000;15:1125-9.[PMID: 11180469]
54. Rabins PV, Blacker D,Rover BW, et al. Prac-tice Guideline forthe treatment ofpatients withAlzheimers diseaseand other demen-tias. Supp Am JPsych. 2007;164:25-7.
55. Knopman DS,DeKosky ST, Cum-mings JL, et al. Prac-tice parameter: diag-nosis of dementia(an evidence-basedreview). Report ofthe Quality Stan-dards Subcommit-tee of the AmericanAcademy of Neurol-ogy. Neurology.2001;56:1143-53.[PMID: 11342678]
2008 American College of Physicians ITC4-12 In the Clinic Annals of Internal Medicine 1 April 2008
with atypical features, such as earlyonset, presence of early neurologicsymptoms, rapid progression, earlypersonality changes, or unusualsymptom patterns.
Consultation with a geriatric psy-chiatrist or dementia specialistshould also be considered for theevaluation or management of
difficult-to-treat psychiatric symp-toms, such as depression, psychosis,or behavioral disturbances, becausethese symptoms cause significantsuffering, can sometimes createdangerous situations for the patientand others, and reduce qualityof life.
Treatment of dementia ideallyincorporates elements of manytreatment modalities, including
preventive medicine, psychoeduca-tion, behavioral therapy, and phar-macotherapy. For optimum care, itis often necessary to interface with abroad range of professionals, includ-ing occupational therapists, socialworkers, physical therapists, andspeech and language pathologists.
When should cliniciansrecommend hospitalization forpatients with dementia?During the assessment of cognitive
impairment, hospitalization shouldbe considered for patients who can-not be evaluated safely or compre-hensively as an outpatient becauseof dangerous behavior, unsafeliving conditions, compromisednutrition, neglected medical condi-tions, or inability to cooperate.
Psychiatric hospitalization is some-times required because of the sever-ity of psychiatric symptoms. For
example, hospitalization should beseriously considered for depressedpatients who exhibit suicidality, sig-nificantly decreased food and fluidintake, delusional depression,immobility, inability to attend toother medical conditions, and aneed for electroconvulsive therapy.
Patients with behavioral distur-bances who are dangerous tothemselves or others, or whocannot be treated safely or success-fully as an outpatient, may needhospitalization. Examples of suchdisturbances include wandering,violence, calling out, hyperphagia,and severely disordered sleepwakecycle. Patients with hallucinationsand delusions may also require hos-pitalization if the symptoms do notrespond to outpatient treatment,require the addition of multiplemedications, cause patient distressand behavioral disturbances, orpresent a danger to others. Involun-tary commitment may be required.
How can clinicians help familiesmake decisions about long-termcare?
Generally, a move into an assisted-living facility or nursing home isprompted by physical limitationsthat cannot be managed at home,such as the need for full assistancewith transferring, ambulation, toi-leting, or feeding. Other patientshave to move because of unman-ageable psychiatric symptoms orcaregivers inability to provide nec-essary care at home (49).
Families with ample financialresources may be able to providemany services at home that usuallyare provided in a facility. Periods ofrespite care may help families delayplacement. Families should be sup-ported and guided through the dif-ficult and painful decision-makingprocess. Clinicians should encour-age families to investigate facilitiesin their region early in the courseof dementia to avoid hurried deci-sion-making should placement in
a long-term care facility becomenecessary.
What specific caregiver needsshould be addressed by theclinician?Caregiving for a patient withdementia is physically and
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emotionally taxing, and inquiringabout caregiver wellbeing is acritical component of longitudinaldementia care. Common caregiversymptoms include guilt, anger,grief, fatigue, loneliness, demoral-ization, and depression. Untreatedcaregiver burden can also worsenthe patients emotional well-being
and lead to nursing home place-ment earlier than may otherwise benecessary (50). Patients symptomsand the consequent demands onthe caregiver change over time, andtherefore monitoring of caregiverwell-being must be conducted atevery visit. Caregivers should beinformed about local respite
programs, and long-term planningshould be supported.
Caregivers should also receiveinformation about local educationalprograms and support groups. Anumber of large, well-conductedtrials have shown that psychoedu-cational and support groups with a
focus on problem-solving, commu-nication, management of behavioraldisturbances, and emotional sup-port are effective in delaying nurs-ing home placement for up to 1year, and in diminishing caregiverand patient depression and patientagitation and anxiety (5153).
56. Assessing Care ofVulnerable Elders(ACOVE). ACOVEQuality IndicatorLibrary. Accessed atwww.acove.com/QI
/Acove.hta on 12February 2008.
2008 American College of PhysiciansITC4-13In the ClinicAnnals of Internal Medicine1 April 2008
Treatment... Clinicians should adopt a broad treatment approach that incorporates
attention to quality of life, cognitive enhancement, management of behavioraland psychiatric symptoms, and caregiver well-being. In considering pharmacologic
therapy for dementia, clinicians should base the decision to initiate an anti-
cholinesterase inhibitor or memantine on individual assessment, taking into
account tolerability, ease of use, and side-effect profile. It is important to identify
and treat psychiatric symptoms, such as depression, psychosis, anxiety, and behav-
ioral disturbances, with both behavioral and pharmacologic treatment to maximize
treatment of cerebrovascular disease risk factors, and to treat any general medical
conditions that could be negatively affecting cognition. Clinicians should attend
to safety issues on an ongoing basis. It is important to attend to caregiver burden
and consider referral to support groups and other psychoeducational activities.
CLINICAL BOTTOM LINE
Practice
ImprovementWhat do professionalorganizations recommend withregard to screening, diagnosis, andtreatment of dementia?Guidelines from professionalorganizations include those from
the American Psychiatric Associa-tion, published in their second edi-tion in 2007 (54), the AmericanAcademy of Neurology, publishedin 2001 (55), and the U.S. Preven-tive Services Task Force, publishedin 2003 (19). The U.S. Preventive
Services Task Force documentstates that there is insufficient evi-dence to recommend general popu-lation screening for cognitive impair-ment. The American Academy ofNeurology guideline covers detec-
tion, diagnosis, and managementof dementia, and the AmericanPsychiatric Association guidelinealso provides comprehensive rec-ommendations on overall care. TheAmerican College of Physicianshas just issued new guidelines on
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2008 American College of Physicians ITC4-14 In the Clinic Annals of Internal Medicine 1 April 2008
the treatment of dementia (31)
based on the results of a systematic
review (32).This guideline and
review emphasize the modest effect
of current drug therapy for dementia
and the importance of individual
patient assessment.
What measures do stakeholders
use to evaluate the quality of care
for patients with dementia?
The Center for Medicare &
Medicaid Serviecs has issued speci-
fications for measures for its 2008
Physicians Quality Reporting Ini-
tiative. Despite lack of evidence for
screening asymptomatic patients for
dementia, one of these measures
relates to dementia and evaluates
the percentage of patients age 65years or older who have documen-
tation of screening for cognitive
impairment using a standardized
tool. Another measure relates to
advance care planning. The Assess-
ing Care of Vulnerable Elders
(ACOVE) quality-of-care measure-
ment program includes specific
quality measures on dementia (56).
What is the role of patient
education in optimizing care of
patients with dementia?
In speaking with patients about
their memory problems and the
necessity to make lifestyle changes,clinicians should consult with
caregivers about appropriate disclo-
sure of the diagnosis and presenta-tion of information. It is important
to determine what the patient
already knows about their condition
and what else he or she wants toknow. Clinicians should address
safety concerns directly with
patients and caregivers and eventu-ally approach long-term issues, such
as management of finances, medical
decision-making, and possible
placement, when appropriate.
It is essential to attend to the needsof the caregiver and to educate
them about the course of dementia
and the challenges they face. Refer-ral to psychoeducational programs
may be helpful in managing care-
giver grief, anger, guilt, demoraliza-
tion, and fatigue. Local respite pro-grams should also be considered.
inthe
clinic
Tool Kitin the clinic
Dementia
PIER Modulespier.acponline.org/physicians/diseases/d224/d224.html
pier.acponline.org/physicians/screening S375/S375.html
Access PIER modules on dementia and screening for dementia
Patient Information Pagewww.annals.org/intheclinic
Download copies of the Patient Information sheet that appears on the following page forduplication and distribution to your patients
Washington University: Alzheimer Diseases Research Center
www.biostat.wustl.edu/adrcGlobal clinical dementia rating
ACOVE Quality Indicator Librarywww.acove.com/QI/Acove.hta
Evidence-based quality indicators to improve health care in older adults
American Academy of Neurologywww.aan.com/professionals/practice/pdfs/dementia_guideline.pdf
Detection, diagnosis, and management of dementia
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WHAT YOU SHOULD KNOWABOUT DEMENTIA
People with dementia get forgetful and can later have problems doing everydaythings, such as eating and getting dressed.
Medicines may help some people with dementia think better and keep from gettingworse for a while.
Keeping active with family and friends also helps people with dementiaThere is no cure for dementia. It usually gets worse over time.
When this happens, it is important to plan for the future.
Web Sites with Good Information about Dementia
Alzheimer Associationwww.alz.org/alzheimers_disease_what_is_alzheimers.asp
ACP Foundation HealthTipsfoundation.acponline.org/files/ht/dem_en.pdf
Family Caregiver Alliancewww.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=569
National Institute on Agingwww.niapublications.org/agepages/forgetfulness.asp
In the Clinic
Annals of Internal Medicine
PatientIn
formation
Caring for People with Dementia
Learn what to expect from the patient you help care for and find out what helphe or she needs.
Keep the patient busy with family and friends and ask about day programs thatkeep him or her active.
Ask the doctor if and when medicines may help and which medicines may makethings worse.
Call the doctor if there are big changes in how the person is acting or thinkingand have a plan for emergencies.
Try to keep the patient from falling, getting lost, or getting hurt.
Get a safe-return bracelet in case the patient gets lost. You can get one from
the Alzheimer Association Safe Return Program at P.O. Box 9307, St. Louis, MO63117-0307; 888-572-8566
Be sure to take care of yourself by asking for help with caretaking; going to jointsupport groups; making time for yourself; staying healthy; and talking to yourdoctor if you feel very tired, sad, stressed, guilty, or burned out.
Make a plan in case you can no longer care for the person at home.
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CME Questions
A 72-year-old woman is brought to theoffice by her son for evaluation of gradu-ally progressive forgetfulness over thepast 18 months. On a recent week-longvisit, she could not learn the name of thehosts dog. She frequently re-reads the
daily paper, and tends to ask the samequestions repeatedly. She has no signifi-cant medical history and no abnormali-ties of gait, posture, coordination, speech,or dexterity. Personality is preserved. Onexamination, vital signs are normal, as isattention. Her score on MiniMentalState Examination is 23/30, and sherecalls 0/3 words after brief distraction.She has difficulty copying a geometricfigure. Neurologic examination is other-wise normal.
Which of the following is the most likelydiagnosis?
A. Alzheimer dementiaB. Frontotemporal dementiaC. Dementia with Lewy bodiesD. Vascular dementia
E. Dementia secondary to vitamin B12
deficiency
A 70-year-old woman is evaluated for anepisode of abrupt cognitive decline thatbegan 2 weeks ago when she was sud-denly unable to read the newspaper dur-ing breakfast. She could not find thebathroom in her own home but couldcarry on a conversation and recognizefamily members. Her condition has sinceimproved. She has a history of hyperten-sion and coronary artery disease, and hasbeen forgetful over the past few years.
On examination, vital signs and generalphysical examination are normal. Herscore on MiniMental State Examinationis 22/30. She is not oriented to time orplace. Neurologic examination is normalexcept for a left Babinski sign. Computedtomographic scan of the head showsbilateral periventricular white matterhypodensity. After 3 months, she is ori-
ented to place and has improved dailyfunction, a score on MiniMental StateExamination of 24/30, and a normal neu-rologic examination, except for theBabinski sign.
Which of the following tests would bemost useful for the diagnosis of thispatients cognitive impairment?
A. Analysis of cerebrospinal fluid for14-3-3 antigen
B. ElectroencephalographyC. Repeat brain imaging
D. Analysis of blood for presenilin 1mutation
A 70-year-old man is evaluated in theemergency department for 2 episodes ofbradycardia and is found to have second-degree atrioventricular block. The patienthas Alzheimer dementia, type 2 diabetesmellitus, hypertension, and coronaryartery disease. His medications aredonepezil (dosage recently increased from5 to 10 mg at bedtime); memantine, 10mg twice daily (also recently started);vitamin E, 1000 IU twice daily; trazodone,50 mg twice daily for agitation; gly-buride; hydrochlorothiazide; pravastatin;
and aspirin.Which of the patients medications islikely to explain these episodes?
A. DonepezilB. GlyburideC. Vitamin ED. Trazodone
A 78-year-old woman is evaluated forprogressive impairments of memory andother aspects of intellect, which havedeveloped insidiously over 3 years. Thepatients score on MiniMental StateExamination is 22/30, and she recalls 0/3words after a 3-minute delay. There areno other significant findings on physicalexamination.
Which of the following is most likely toimprove this patients symptoms?
A. Vitamin EB. Ginkgo bilobaC. Central cholinesterase inhibitorD. MemantineE. Estrogen
An 82-year-old woman with Alzheimerdisease presents with her family for eval-
uation of worsening mental status. Shehas been taking galantamine for 3 years.Initially after treatment, her memory andattentiveness improved slightly, but shelater declined and she cannot now man-age her financial affairs and sometimesfails to recognize long-time acquain-tances. Her score on the MiniMental
State Examination has fallen from 22/30to 14/30. There are no other significantfindings on physical examination.
Which of the following medicationsshould be added to her treatmentregimen?
A. Vitamin E
B. Ginkgo biloba
C. Risperidone
D. Memantine
E. Estrogen
A 78-year-old man is brought to theoffice by his family for evaluation of con-
fusion and memory problems, which havebeen worsening over the past 6 weeks.Initially, his symptoms were evidentmainly in the morning, but they nowseem to occur throughout the day. He
wanders from the house and sometimesdoes not recognize his wife. He has visualhallucinations, and, while sitting in thekitchen, believes that he is on a bus. Hismedical history includes type 2 diabetes
mellitus with painful peripheral neuropa-thy, coronary artery disease, depression,and congestive heart failure. Medicationsinclude glyburide, nortriptyline, digoxin,
lorazepam, metoprolol, lisinopril, aspirin,and pravastatin. His daughter does notknow how long he has been taking thesemedications. There is no family history of
neurologic disease.On examination, the patient has asterixisand findings consistent with peripheralneuropathy. He is mildly lethargic and
inattentive, and not oriented to time orplace. His score on the MiniMentalState Examination is 13/30, and herecalls 2/3 words after a delay. Electrolytelevels, oxygen saturation, liver and renal
function, and computed tomographicscan of the head without contrastare normal.
Which of the following conditions is most
likely the cause of the patients cognitiveimpairment?
A. Alzheimer disease
B. Dementia with Lewy bodies
C. Depression
D. Cerebrovascular disease
E. Toxic encephalopathy
Questions are largely from the ACPs Medical Knowledge Self-Assessment Program (MKSAP). Go to www.annals.org/intheclinic/
to obtain up to 1.5 CME credits, to view explanations for correct answers, or to purchase the complete MKSAP program.
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