THE CASE: A 72-year-old farmer is brought by his daughter for a comprehensive
geriatric assessment. His previous history is unremarkable. The patient
reports that he has had vivid visual hallucinations, which he calls "visitors." He becomes frightened
and hostile when these incidents occur; on several occasions, he has exhibited violent behavior
as persons around him tried to calm him. Although the patient was able to recall each episode in
detail, he felt as if he had watched it from a distance and had not been an active participant.
The patient also has experienced dizziness on standing and repeated falls. He is depressed
because he is unable to participate in previous activities, such as driving and gardening. His
daughter describes fluctuations in cognition that result in "good" and "bad" days. She feels he is
having a "good" day at the time of his evaluation.
Examination reveals orthostatic hypotension with no change in pulse on standing. Cardiovascular
examination is otherwise unremarkable. Neurologic examination results are normal.
Folstein Mini-Mental State Examination score is 20/30. Most notable are deficits in visuospatial
ability out of proportion to other cognitive deficits. The patient completed only a 4th-grade education
and is unable to spell "world" or write a sentence. He misses 1 of 3 items on delayed recall.
He is unable to organize a clock drawing.
What is the differential diagnosis for this pattern
of cognitive impairment?
Alzheimer dementia (AD) is the
most common type of dementia; it affects
50% to 70% of patients with dementia.
This is followed by vascular
dementia (VaD), dementia with Lewy
bodies (DLB) and frontotemporal dementia
(FTD), which affect 10% to
20%, 10% to 15%, and 5% to 15% of dementia
Although there is no cure for dementia,
it is a chronic disease process
like many others-such as diabetes
and heart failure-in which a clinician's
guidance can have profound
impact on a patient's symptomatology
and quality of life. Early detection is
important because pharmacologic
and nonpharmacologic measures can
slow disease progression. However,
unlike other medical illnesses, dementia
is often not detected and addressed
until its later stages. Because
dementia affects activities of daily living,
patients can present with medical
noncompliance and malnutrition long
before physicians and family are
aware of the presence of dementia.
The diagnosis and treatment of
AD were reviewed in an earlier article
in this series (Consultant, March
2004, page 388). The focus of this
article is the non-Alzheimer dementias:
their diagnosis, treatment, and
The field of non-AD research
is evolving. Consensus groups from
the fields of internal medicine, family
practice, geriatrics, psychiatry,
and neurology agree that dementia
may be described as progressive
decline in 2 or more areas of cognition
to the point of impairment
in social or occupational functioning.
There is also agreement on the
symptoms of AD. However, there is
no consensus on the criteria for
non-Alzheimer dementias. Evidencebased
reviews show that current
clinical criteria are inadequate, because
most lack sensitivity and/or
specificity compared with autopsy
data. This article is based on current
clinical guidelines and provides
common language and definitionsfor use in the diagnosis and management
This broad category includes
many vascular diseases that can lead
to dementia (Table 1). Multi-infarct
dementia is no longer classified as a
major type of dementia; it is now considered
one type of VaD.
Neuroimaging studies complicate
the diagnosis because of the
high prevalence of white matter
changes seen in these studies.
These changes are not necessarily
pathologic, nor are they always associated
with clinical symptoms, but
their presence may lead some clinicians
to overdiagnose VaD. It is
more likely that vascular disease in
general contributes to the clinical
outcomes of dementia. This conclusion
is based on the results of the
Nun Study, which showed that lacunar
infarcts increased the risk of clinical
dementia 20-fold, and that patients
with VaD had fewer senile
plaques and neurofibrillary tangles
than patients with AD before signs
of dementia appeared. 1History. Diagnosing VaD is
straightforward when patients have
cognitive deficits after an obvious
cerebrovascular event. However, the
diagnosis is more challenging when
multiple silent cerebral infarctions
have led to cognitive impairment. In
fact, current guidelines do not include
this condition under the broad category
of VaD, even though many clinicians
use this criterion in practice.
The controversy surrounding this
question continues to evolve. Urinary
dysfunction and gait disturbance have
been suggested as early markers of
VaD.2Diagnosis. The National Institute
of Neurological Disorders and
pour la Recherche et l'Enseignement
en Neurosciences (NINDS-AIREN)
criteria are still widely used as a tool
for the diagnosis of VaD, even though
they lack sensitivity (Table 2). Because
memory may be only minimally
affected, it is important to measure
other areas of cognitive function,
such as language, visuospatial ability,
praxis, and executive function. The
pattern of cognitive deficits depends
on the location of the cerebral injury.
Gait impairment often presents as
short, shuffling steps similar to those
seen in patients with Parkinson disease.
Patients are more apathetic
than those with AD.
Treatment. Regardless of the diagnosis,
vascular risk factors-such
as diabetes and hypertension-should
be controlled to prevent ischemic
damage, especially in those with VaD
resulting from ischemia. Progression
of the disease is highly variable. Some
evidence suggests that cholinesterase
inhibitors slow disease progression.3DEMENTIA WITH LEWY BODIES
Although the criteria for DLB
(Table 3) lack the sensitivity and
specificity of criteria for AD, it is important
that a diagnosis be made-
not only for family education but for
prognosis and other clinical implications
History. Families often report
prominent behavioral and neuropsychiatric
changes before the onset of
short-term memory loss. However,
the order of symptom onset varies
and may depend on the cortical location
of the Lewy bodies. Patients may also exhibit substantial fluctuations in
alertness or cognition. A history of
repeated falls, syncope, and neuroleptic
sensitivity suggests DLB. Patients
tend to be more apathetic than those
with AD. Many patients with DLB
have rapid eye movement (REM)
sleep disorders.4-6Diagnosis. On mental status examination,
patients with DLB typically
show prominent behavioral changes,
executive dysfunction, and visuospatial
dysfunction out of proportion to
memory loss. Heightened sensitivity
to neuroleptic agents predicts a
greater likelihood of extrapyramidal
side effects. Parkinsonism may or
may not be present at the time of evaluation.
Rigidity is seen in about 75% of
patients; tremor is atypical. Neuroimaging
is usually part of the workup.
Treatment. The recommended
approach involves management of the
prominent symptoms. Some evidence
suggests that treatment with cholinesterase
inhibitors is associated with
diminished hallucinations and improvements
in behavior and cognition.
7 Antiparkinsonian medications,
such as levodopa, which may be necessary
to treat prominent motor
symptoms, usually exacerbate hallucinations
and confusion. To manage
psychotic symptoms, it is best to reduce
or eliminate the antiparkinsonian
medications first. However, in order to
avoid neuroleptic sensitivity, psychotic
symptoms should be treated only if
they are disturbing to the patient.
Neuroleptic medications such as quetiapine,
which are less likely to cause
extrapyramidal side effects, may also
be helpful in mitigating psychotic
symptoms. If a REM sleep disorder is
present, low-dose clonazepam can be
helpful. Selective serotonin reuptake
inhibitors (SSRIs) are the agents of
choice for anxiety or depression.
DLB usually progresses more
rapidly than AD; however, the duration
varies greatly. The average is 6.4
years. Patients' insight into their
deficits can make it difficult for families
to implement a care plan that
may decrease patients' independence.
The fluctuations in cognition can also
make caregiving extremely difficult
because of the unpredictable nature
of the disease process.
Pick disease was the initial prototype
for this category of dementia,
but several similar clinical syndromes
have been identified that do not have
the same pathologic changes seen in
Pick disease. These are now subsumed
under the rubric of FTD.
History. Patients typically present
with prominent frontal lobe
changes, such as personality and language
disturbances (Table 4).The
hallmark behavioral change is poor
judgment. In addition, patients usually
demonstrate either disinhibition or
apathy. Families often report socially
inappropriate actions or language.
Drastic personality changes may
occur long before memory impairment
becomes apparent. Executive
dysfunction and prominent language
abnormalities are also reported.
Diagnosis. Because FTD is uncommon,
it has been more difficult
to evaluate the diagnostic criteria. In
research, functional imaging with
single-photon emission CT and
positron emission tomography can
increase confidence in a clinical diagnosis;
however, these tools have
limited use in office practice. Neuropsychological
testing and sometimes
geropsychiatric evaluation may be
considered for patients with suspected
Treatment. The course is progressive
and tends to be more rapid
than that of AD. No treatment is currently
History. Patients present with a
rapidly progressive dementia.
Diagnosis. The classic triad of
CJD involves dementia, myoclonus,
and a distinctive periodic discharge
pattern on electroencephalography.
At least 2 of the following motor disturbances
must be present for the diagnosis:
myoclonus, extraocular or
cerebellar disturbance, pyramidal/extrapyramidal
dysfunction, and akinetic
mutism. A positive 14-3-3 assay for
cerebrospinal fluid is included in the
diagnostic criteria; however, a negative
assay does not rule out CJD.
vCJD has atypical clinical features:
the presence of prominent psychiatric
or sensory symptoms at the
time of clinical presentation or early
in the course of the illness, delayed
onset of neurologic abnormalities, duration
of illness of at least 6 months,
and a diffusely abnormal nondiagnostic
Treatment. No treatment is currently
Other causes of dementia are
found in fewer than 1% of patients
with dementia (Table 5).
RESOURCES FOR SUPPORT
Although current treatments for
dementia do not affect the underlying
disease process, a clinician's knowledge
of the various types of dementia
and their key features can assist families
and patients in their understanding
of certain behaviors. If the diagnosis
is made early enough, understanding
the disease helps patients
participate in planning for future care.
As the diseases progresses, family
members can benefit from understanding
how dementia affects cognitive
Although making the correct diagnosis
and providing appropriate
treatment are important, providing
the caregiver with guidance and support
is even more challenging and
more critical. Most primary care clinicians
are not able to provide ongoing
support. However, a number of local
and national organizations offer this
help. The National Association of Area
Agencies on Aging (www.n4a.org or
800-677-1116) and the Alzheimer's
Association (www.alzheimers.org or
800-272-3900) are excellent places to
start. The Alzheimer's Association assists
caregivers of patients with AD as
well as those with other types of memory
loss. In some areas, local geriatric
assessment centers are equipped with
the resources for ongoing caregiver
OUTCOME OF THIS CASE
A diagnosis of DLB was made.
The patient's CT scan and laboratory
data were unremarkable. The patient
was given quetiapine to help manage
his hallucinations and to help limit
neuroleptic sensitivity. With weekly
dosage increases, the hallucinations
were eventually controlled. Donepezil
was initiated on the return visit. The
patient's depression improved withthe addition of an SSRI. A safety
check was done in the patient's home
to prevent falls. He was instructed to
rise slowly from a seated position and
pump his fists and legs before rising
to prevent orthostatic hypotension.
Both measures helped when the patient
remembered to do them. One
year later, the patient was still living at
home and was able to function independently.
Visual hallucinations persisted
but were no longer threatening.
The violent outbursts have not
1. Snowdon DA, Greiner LH, Mortimer JA, et al.
Brain infarction and the clinical expression of
Alzheimer disease. The Nun Study. JAMA. 1997;277:
2. Kotsoris H, Barclay LL, Kheyfets S, et al. Urinary
and gait disturbances as markers for early multiinfarct
dementia. Stroke. 1987;18:138-141.
3. Erkinjuntti T, Kurz A, Gauthier S, et al. Efficacy
of galantamine in probable vascular dementia and
Alzheimer’s disease combined with cerebrovascular
disease: a randomized trial. Lancet. 2002;359:
4. Knopman DS, Boeve BF, Petersen RC. Essentials
of the proper diagnoses of mild cognitive impairment,
dementia, and major subtypes of dementia.
Mayo Clin Proc. 2003;78:1290-1308.
5. Ferman TJ, Boeve BF, Smith GE, et al. Dementia
with Lewy bodies may present as dementia and
REM sleep behavior disorder without parkinsonism
or hallucinations. J Int Neuropsychol Soc. 2002;8:
6. Turner RS. Idiopathic rapid eye movement sleep
behavior is a harbinger of dementia with Lewy bodies.
J Geriatr Psychiatry Neurol. 2002;15:195-199.
7. McKeith I, Del Ser T, Spano P, et al. Efficacy of
rivastigmine in dementia with Lewy bodies: a randomised,
double-blind, placebo-controlled international
study. Lancet. 2000;356:2031-2036.
8. Geldmacher DS. Contemporary Diagnosis and
Management of Alzheimer’s Dementia. Newtown, Pa:
Handbooks in Health Care Co; 2003.
9. Roman GC. Vascular dementia: distinguishing
characteristics, treatment, and prevention. J Am
Geriatr Soc. 2003;51(suppl 5):S296-S304.
10. McKeith IG, Burn D. Spectrum of Parkinson’s
disease, Parkinson’s dementia, and Lewy body
dementia. Neurol Clin. 2000;18:865-883.