MORE ON DEMENTIA
From the Treatment of Alzheimer’s and Related Disorders, presented by Johns Hopkins Alzheimer’s Disease Research
Center and the Copper Ridge Institute
| HOW IS THE DIAGNOSIS OF DEMENTIA MADE? —Richard O’Brien, MD, PhD, Associate Professor of Neurology,
Johns Hopkins University School of Medicine, Baltimore
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| Etiology: Alzheimer’s disease (AD)—most common cause of dementia; parkinsonian features absent; family history generally
not relevant; behavior changes tend to occur in late stages of disease (except depression, which often occurs early);
diffuse Lewy body disease—classic parkinsonian dementia; patients often have visual hallucinations early in course of
disease; frontotemporal dementia (FTD)—patients younger than in other forms of dementia; parkinsonian features absent;
family history of FTD common; changes in personality (eg, disinhibition or apathy) occur early in course of disease;
vascular disease—dementia often indistinguishable from AD
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| Evaluation: screen patients who failed screening for dementia (eg, Mini Mental Status Examination [MMSE]), patients who
complain of memory problems (low yield for dementia), and patients whose family members complain of memory problems
(high yield for dementia); function—Functional Activities Questionnaire (FAQ) helpful for assessing function; asking informant
about level of comfort in leaving patient alone for 1 to 2 days useful in assessing level of function
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| Memory testing: Hopkins Verbal Learning Test (recommended by speaker); list of 12 words, divided into 3 categories,
read aloud at rate of 1 word/sec; patient then lists as many words as he or she can remember (repeat list and recall 2 more
times); after 20 min, patient asked to recall words from list (ie, delayed recall); table included for scoring test; note—
avoid confusing patient by giving more words to learn before testing delayed recall
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| Other diagnostic tests: orientation—date; location; time; small inaccuracies (eg, incorrect about date by 1-2 days) likely
not significant; attention—patient spells “WORLD” forward and backward; patient lists months of year in reverse order
; calculations—addition or subtraction of numbers with ≥2 digits; calculating number of quarters in $6.75; other
tests of attention—patient connects numbers in order (Trails A) or alternating numbers and letters (Trails B); slow time
for completion and errors indicate problem with attention; spatiotemporal skills—patient draws cube or clock with
hands indicating specific time; dysmorphic drawing or clock with inaccurately placed or missing hands correlates with
diagnosis of dementia
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| Neurologic examination: signs of parkinsonism (eg, abnormal gait); subtle signs of stroke (eg, problems with visual field,
orbit sign, difficulty tapping foot); tests of praxis (eg, flip coin, turn key, Luria 3-step)
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| More memory assessment: once above tests completed (should take ≈20 min), test delayed recall; test recognition memory
by reading list of 24 words, then asking patient to identify those words on original list
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| Language tests: confrontational naming—Boston Naming Test or National Institutes of Health (NIH) Stroke Scale; tests
generally do not recognize mild dementia; verbal fluency—patient names as many animals (or words that start with “F,”
for example) as possible in 1 min; <10 words considered abnormal
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| Mini Mental Status Examination: good test for assessing orientation and following progression of disease; score <24 usually
indicates dementia; poor assessment of memory, language, and visuospatial skills; test takes 5 to 7 min to administer
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| Dementia and depression: comorbidity common; screening questions for depression—feelings of sadness, depression,
or hopelessness during past month; degree of interest or pleasure in doing things during past month; asking about irritability
also useful (common symptom of depression in older patients); quantitation of depression—Center for Epidemiologic
Studies Depression Scale (CES-D); self-rating of various symptoms of depression; asking about delusions,
hallucinations, and changes in personality important in all patients with suspected dementia (affects diagnosis and treatment)
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| Strokes: cerebrovascular disorder synergistic with AD, leading to more severe dementia; ≈20% of elderly patients have evidence
of asymptomatic strokes on MRI; patients with history of asymptomatic strokes have higher incidence of dementia;
work-up—evaluate carotid arteries, blood pressure, and cholesterol; although no conclusive data exist to show
relationship between treatment of cerebrovascular risk factors and decreased risk for stroke, treat risk factors appropriately
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| Other abnormalities on MRI: large ventricles—generalized atrophy of brain leads to enlarged ventricles (better indicator
of atrophy than gross inspection of gyri and sulci); patients with normal-pressure hydrocephalus have large ventricles
but no evidence of atrophy and often present with parkinsonian symptoms (refer these patients to specialist); draining
cerebrospinal fluid (CSF) in patient with AD may cause subdural hematomas, infections, or other complications; white-
matter abnormalities—although patients with significant changes in white matter have mild cognitive abnormalities (1-
2 points lower on MMSE), incidence of dementia does not increase independently of history of strokes; focal unilateral
atrophy—distinguishable from strokes by lack of ischemia; associated with FTD; typically localized in temporal, parietal,
or frontal lobes; atrophy of hippocampus—region of brain important in creating new memories; atrophy evident in
patients with mild clinical impairment (MCI); however, atrophy also occurs with normal aging; therefore, clinical significance
unclear at this time
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| Positron emission tomography (PET): technology approved for assessment of patients with AD, but speaker does not
recommend; although study found association between bilateral focal hypometabolism in parietal lobes and progression
to AD, patients in study already had MMSE score of 24 (indication of moderate dementia); 20% of patients without
abnormal PET scans progressed to AD in 2 yr, and 10% of patients with abnormal PET scans did not progress;
minimal diagnostic benefit
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| Imaging amyloid: radiolabeled affinity ligands bind to amyloid peptide; increased formation of plaques may predict risk
for AD 10 yr before patient presents with cognitive abnormalities; application for preventive management not yet available
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| Laboratory testing: reversible dementia rare (≈1% of cases); testing for patients with suspected dementia should include
comprehensive metabolic panel, vitamin B12 , and thyrotropin (TSH); VDRL test optional; test for HIV useful in some
populations of patients; CSF—lumbar puncture (LP) to look for evidence of inflammation reasonable in patients with
unusual presentations (eg, suspected lymphoma of central nervous system [CNS], vasculitis, or Creutzfeldt-Jacob disease);
inflammatory markers do not aid diagnosis in older patients with chronic dementia; ratio of CSF proteins Abeta
and tau may indicate AD, but not likely to have clinical relevance in most patients
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| Genetic testing: autosomal dominant inheritance—rare in AD; more common in FTD (10%-20% of cases); easy to
identify if family history known; family history of AD—having first-degree relative with AD increases risk by ≈1.5-fold
(if onset late in relative) to 4-fold (if onset early in relative); apolipoprotein E (apoE) gene—patients homozygous for
apoE4 have 8- to 18-fold increase in incidence; ≈58% of population heterozygous for apoE4, which increases incidence
by 3- to 5-fold; lifetime risk in patients homozygous for apoE4 50% to 60%; conclusion—in absence of family history
of autosomal dominant disorder, genetic testing not helpful
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| Cognitive patterns: cortical—problems with memory (encoding and recall) predominate; paraphasic errors common; patients
have poor spatiotemporal skills; pattern common in patients with AD; subcortical—memory less affected (some
problems with learning, but recognition memory intact); patients have problems with attention (eg, Trails B and verbal
fluency); associated diseases include vascular dementias, multiple sclerosis (MS), depression, parkinsonism, and FTD
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| TREATING DEPRESSION IN PEOPLE WITH DEMENTIA —Paul B. Rosenberg, MD, Assistant Professor of Psychiatry
and Behavioral Science; Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine,
Baltimore
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| Depression and AD: depression affects ≈25% of patients with AD, presenting as atypical affective syndrome; diagnosis often
difficult; treatment critical in managing dementia; symptoms—depression part of spectrum of neuropsychiatric disturbance;
data from Cache County Study showed 60% of patients with dementia had ≥1 neuropsychiatric symptom; \>40% of
demented patients depressed and ≈50% apathetic; other studies have cited prevalence of depression in patients with AD
from 1% to 50% (wide range partly due to differences in criteria used to define depression); conclusions—criteria defined
by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) too narrow to capture depression
in most patients with dementia; common symptoms include agitation, delusions, anxiety, decreased motivation, and anhedonia;
guilt, poor self-esteem, suicidal ideation, and disturbances in sleep and appetite less common than in younger patients
with depression; delusions common, and hallucinations may occur
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| Psychologic factors in depression in AD: equally prevalent among patients at all stages of disease; not clearly related to
degree of insight into illness; correlated with increased dependency; possibly related to expressive and receptive aphasia;
affected by restrictions of activity
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| Impact on patients and caregivers: depression associated with decreased cognition and daily functioning, agitation, depression
in caregiver, and possibly with earlier institutionalization; mood changes in patient add to caregiver burden, independent
of cognitive and functional decline
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| Neurobiologic findings: possible cell loss in brainstem nuclei containing cell bodies of noradrenergic and serotonergic
neurons; apoE2, although protective of developing AD, associated with depression in AD; on PET, mood symptoms associated
with hypometabolism of frontal cortex, and apathy associated with hypometabolism of anterior cingulate
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| Correlations: patients with AD vulnerable to depression; onset of depression late in life correlates with increased risk for
dementia; depression in elderly patients possibly related to small-vessel vascular disease (vascular depression hypothesis);
some depression associated with executive dysfunction; vascular changes may accelerate onset of AD
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| Assessment: depression presents as affective disorder more commonly than as depressive disturbance; symptoms fluctuate
often; changes in neurovegetative state may occur; delusions common (often persecutory or victimizing); assessment
scales—Cornell Scale for Depression in Dementia ([CSDD]; preferred by speaker); Neuropsychiatric Inventory; information
from caregiver critical, because cognitive defects may inhibit patient’s ability to assess mood accurately; interviewing
patient and caregiver separately often helpful; other assessment scales—Hamilton Depression Rating Scale
(HAM-D) not recommended for patients with dementia; self-administered Geriatric Depression Scale (GDS) not appropriate
in later stages of dementia; effect of caregiver mood—study found depression and other caregiver variables affected
rating of patient mood early on, but effect decreased with time
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| Causes of depression: medical condition (treat cause; provide supportive care); environmental stressor or precipitant (modify
environment, if possible); difficulties in relationship between patient and caregiver or uninformed caregiver (educate caregiver;
develop new routines); cognitive impairment (identify precipitants; intervene early during escalation; educate caregiver);
recurrence of premorbid depression; medical mimics—Parkinson’s disease; MS; hypothyroidism; neurosyphilis;
occult cancer; medications that may cause depressive symptoms include benzodiazepines, digoxin, lithium, phenytoin (Dilantin),
opioids, tricyclic antidepressants (TCAs), and anticholinergic agents; laboratory tests—neuropsychiatric tests typically
performed before onset of depression; other tests include blood glucose, metabolic panel, complete blood count (CBC), thyroid
panel, and urinalysis (urinary tract infections common cause of acute change in mental status)
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| Treatment: antidepressants widely used; psychosocial therapies center around structuring day and therapeutic recreation;
caregiver interventions critical; little research published on nonmedical treatments
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| Antidepressants: positive and negative results occur with equal frequency in literature; Depression in Alzheimer’s Disease
Study (DIADS)—small study found 84% of patients on sertraline had partial or full response (compared to 34% of
patients on placebo); activities of daily living (ADL) function stabilized in patients treated with sertraline, but continued
to decline in placebo group; among responders, improvement in mood occurred within 3 wk; large replication trial under
way; medications—begin with selective serotonin reuptake inhibitor ([SSRI]; speaker prefers escitalopram [Lexapro]);
expect response within 1 mo; if no response, rethink diagnosis, consider need for additional medication (eg, antipsychotic
agent), or switch to different class of drug; consider electroconvulsive therapy (ECT) in cases of severe depression
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| Psychosocial treatments: all appear equally effective; pleasant events schedule similar to reminiscence therapy; therapeutic
recreation targeted toward functional level; exercise; peer volunteer programs; activities that use intact remote memory
(eg, trivia games and mock weddings); music therapy
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| Support for caregiver: practical support—safety issues (eg, driving, cooking, wandering); practical-skills training; respite
care; realistic expectations; emotional support—validation; ventilation and grief work; planning for future care and possible
institutionalization; support groups; 4 pillars of care—supportive care for patient; supportive care for caregiver; treatment of
disease (eg, managing vascular risk factors); treatment of symptoms
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Educational Objectives
| The goal of this activity is to provide information about the diagnosis and treatment of elderly patients with dementia and
depression. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Identify candidates for assessment of dementia.
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| 2. Perform cognitive evaluation of patients with suspected dementia.
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| 3. Discuss uses of imaging and genetic testing in the diagnosis of dementia.
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| 4. Recognize and treat depression in patients with dementia.
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| 5. Identify medical conditions and medications that may cause depressive symptoms in older adults.
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Discussed on This Program
Digoxin [Digitek, Lanoxicaps, Lanoxin]
Escitalopram oxalate [Lexapro]
Lithium [Eskalith, Eskalith CR, Lithium Carbonate, Lithium Citrate, Lithobid, Lithonate, Lithotabs]
Phenytoin sodium [Dilantin]
Sertraline HCl [Zoloft]
Suggested Reading
Barrett AM: Is it Alzheimer’s disease or something else? Ten disorders that may feature impaired memory and cognition.
Postgrad Med 117:47, 2005; Bellilli G, et al: Results of a multi-level therapeutic approach for Alzheimer’s disease subjects
in the “real world” (CRONOS project): a 36-week follow-up study. Aging Clin Exp Res 17:54, 2005; Bourre JM: Dietary
omega-3 fatty acids and psychiatry: mood, behavior, stress, depression, dementia, and aging. J Nutr Health Aging
9:31, 2005; Cosentino SA, et al: The clinical diagnosis of vascular dementia. A comparison among four classification systems
and a proposal for a new paradigm. Clin Neuropsychol 18:6, 2004; Gatz JL, et al: Do depressive symptoms predict
Alzheimer’s disease and dementia? J Gerontol A Biol Sci Med Sci 60:744, 2005; Grossberg GT, et al: Cholinesterase inhibitors
across stages of dementia and cognitive impairments in the elderly. CNS Spectr 10(6 Suppl 5): 1, 2005; Kaufer DI:
Reduction of caregiver burden in Alzheimer’s disease by treatment with galantamine. CNS Spectr 10:481, 2005; Mosconi
L: Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease. FDG-PET studies in MCI and AD.
Eur J Nucl Med Mol Imaging 32:486; Nagga K, et al: Evaluation of factors of importance for clinical dementia diagnosis.
Dement Geriatr Cogn Disord 19:289, 2005; Padovani A, et al: Advances on biological markers in early diagnosis of
Alzheimer’s disease. Adv Clin Chem 39:107, 2005; Paulino Ramirez Diaz S, et al: The need for a consensus in the use of
assessment tools for Alzheimer’s disease: the Feasibility Study, a European Alzheimer’s Disease Consortium’s survey. Int J
Geriatr Psychiatry 21:20, 2005; Shin IS, et al: Neuropsychiatric symptoms and quality of life in Alzheimer’s disease. Am
J Geriatr Psychiatry 13:469, 2005; Starkstein SE, et al: On the overlap between apathy and depression in dementia. J
Neurol Neurosurg Psychiatry 76:1070, 2005; van der Cammen TJ, et al: Genetic testing has no place as a routine diagnostic
test in sporadic and familial cases of Alzheimer’s disease. J Am Geriatr Soc 52:2110, 2004.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Drs. O’Brien and Rosenberg were recorded in Baltimore, at Treatment of Alzheimer’s and Related Disorders, sponsored
by Johns Hopkins University School of Medicine and Copper Ridge Institute, and held March 12, 2005. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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