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Evidence-Based Reviews


Identify and manage 2 common non-Alzheimer’s dementias

Rapid memory loss, visual hallucinations, recent stroke differentiate vascular, Lewy body subtypes

Vol. 3, No. 12 / December 2004
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Primary care doctors refer patients with dementia to psychiatrists when the diagnosis or disease course is unclear. Psychiatrists thus must often discern non-Alzheimer’s dementias— particularly the vascular and Lewy body types— from Alzheimer’s dementia. This article describes:

  • features that distinguish vascular, Lewy body, and Alzheimer’s dementias
  • cognitive and medical tests to help determine dementia type and facilitate treatment
  • risk factors that promote cognitive and functional decline
  • strategies for using medication while minimizing side-effect risks.

CASE REPORT: DISRUPTIVE IN DAY CARE

Ms. Z, age 82, is referred to a psychiatrist after numerous failed attempts by her primary care physician to stop her medical and psychiatric deterioration.

Table 1

Estimated dementia type prevalence among patients with dementia

Dementia type

Prevalence

Alzheimer's

65%

Lewy body

0-15%

Vascular

10-15%

Mixed

10-15%

Source: reference 1

The patient was functioning well at home until 6 months ago, when her husband’s death triggered a dramatic functional decline. She has Parkinson’s disease and has had dementia symptoms for 3 years, but family members do not recall a dementia diagnosis.

Ms. Z has become increasingly disruptive in day care; she yelled at and slapped a staff member during one episode. Her son is concerned that additional outbursts will prompt her dismissal. Her Mini-Mental State Examination (MMSE) score is 19, indicating moderate dementia.

Donepezil, 10 mg/d across 2 years, has not slowed Ms. Z’s memory decline. Carbidopa/levadopa, 25/250 mg tid over 1 year, has not improved her Parkinson’s symptoms. Risperidone, 0.5 mg bid, caused marked sedation and unsteady gait and was stopped after 4 weeks. She also is taking hydrocodone/acetaminophen, 5/500 mg/d for osteoarthritis, and lisinopril/hydrochlorothiazide, 10/12.5 mg/d for hypertension.

Discussion. As with Ms. Z, a significant other can mask a dementia patient’s cognitive deficits, but these deficits become apparent after the partner dies. Family members then discover that a parent or sibling cannot function independently.

Treatment should target Ms. Z’s aggression to allow her to stay in day care and her son to care for her at home. Determining the dementia type is crucial to planning treatment and preserving function.

WHICH DEMENTIA IS WHICH?

Non-Alzheimer’s dementias account for up to 35% of dementia cases (Table 1).1 The pathologic correlations separating Alzheimer’s, vascular, and Lewy body dementias are often confusing:

  • Beta-amyloid plaques are common in Alzheimer’s and Lewy body dementias, although neurofibrillary tangles are much less common in the Lewy body type.
  • Synaptic cholinergic deficiencies are seen in Alzheimer’s and vascular dementias.
  • Hypertension and hyperlipidemia—both traditional vascular risk factors—also appear to contribute to Alzheimer’s dementia.

Vascular dementia. Large, single-vessel hemispheric infarcts cause substantial damage, whereas multiple small vascular lesions (such as lacunae or mini-infarcts) can have more-subtle effects when strategically located, such as in the basal ganglia, hippocampus, or thalamus. These smaller lesions can disrupt frontal cortical-subcortical neural pathways and contribute to difficulties with executive functions (judgment, insight), emotional control, and behavior.

Lesions from a cerebrovascular accident, however, do not necessarily cause dementia, and the mechanism by which lesions cause dementia is not fully understood. Post-stroke dementia sometimes is progressive, suggesting a degenerative rather than vascular cause.

Lewy body dementia is associated with Parkinson’s disease, as Lewy body inclusion deposits are common to both disorders. The deposits typically appear in the cerebral cortex in Lewy body dementia but not in Parkinson’s.

Amyloid protein deposits alter the clinical presentation. Patients with these lesions have fewer visual hallucinations and motor problems, making diagnosis more difficult.

Lewy body dementia, like all major dementias, usually surfaces after age 75. Its clinical course generally is considered worse than that of Alzheimer’s dementia, but these two dementia types do not differ substantially in age of onset, age of death, or survival rates.

Table 2

Clinical features that characterize Lewy body dementia

Central

Progressive cognitive decline that interferes with normal social and occupational function; deficits on tests of attention, frontal-subcortical skills, and visuospatial ability can be especially prominent

Core

Two of three needed for probable diagnosis:

  • Fluctuating cognition with pronounced variations in attention, alertness
  • Recurrent visual hallucinations that are typically well formed and detailed
  • Spontaneous parkinsonism features

Supportive

Repeated falls
Syncope
Transient loss of consciousness
REM sleep behavior disorder
Systematized delusions
Hallucinations in other modalities
Neuroleptic sensitivity
Depression

Features less likely to be present

History of stroke
Another physical illness or brain disorder that interferes with cognitive performance

Source: reference 6

FEATURES OF VASCULAR DEMENTIA

Onset can be gradual but is more often sudden— usually occurring shortly after an ischemic stroke. Disease progression can be gradual or dramatic, depending on the vascular event type. Cognitive and physical decline in vascular dementia usually is stepwise over time, whereas decline in Alzheimer’s dementia is more gradual with progressive severity.

Patients with vascular dementia classically present with memory loss temporally associated with other typical stroke stigmata. Brain imaging often uncovers evidence of stroke that is otherwise not clinically evident.

CNS manifestations of vascular dementia often include memory loss, emotional lability (including depression), and executive-task dysfunction. Patients usually have atrial fibrillation or vascular risk factors, including diabetes mellitus, hypertension, hyperlipidemia, obesity, or tobacco use. Patients with previous stroke, coronary artery disease, or peripheral vascular disease are at increased risk.

Vascular dementia is categorized by stroke type:

Embolic infarct. Emboli, typically cardiac in origin, can occlude small or large cerebral arteries, resulting in correspondingly sized infarcts. Atrial fibrillation can promote areas in the atria with relatively low flow turbulence. Blood clots can form that eventually embolize via the carotid arteries. Multiple emboli can occur, causing progressive dementia.

Cerebral hemorrhage —small or large—can be devastating. Hypertension is the major risk factor for this form of stroke.

Multi-infarct dementia. Multiple cerebral blood vessel infarcts classically lead to stepwise functional decline after each event. Multiple small infarcts can occur in various brain regions, including the cortex and basal ganglia. Binswanger’s disease, a variant of vascular dementia in which incomplete ischemia is limited to the hemispheric white matter, tends to be fairly progressive.2

Small-vessel disease. Reduced blood flow and tissue perfusion can cause small-vessel disease. Often the ischemia is “silent,” detectable only on MRI or CT. The infarcts typically cause lacunar lesions, nerve demyelination, and gliosis.3 These can occur to some extent in nondemented patients but become significant with more-extensive disease.

FEATURES OF LEWY BODY DEMENTIA

As with all dementias, permanent memory loss must be present to diagnose this dementia sub-type. Overall cognitive deficits may be more prominent than memory loss, however. The patient may have trouble performing cognitive tasks that employ visuospatial abilities, executive functions, and attention. Neuropsychiatric symptoms that overlap with Alzheimer’s dementia include apathy, anxiety, agitation, depression, anhedonia, and paranoia.

The presence of visual hallucinations, fluctuating cognition, or extrapyramidal symptoms (EPS) distinguish Lewy body from Alzheimer’s dementia.

Visual hallucinations are prominent in Lewy body dementia and often prompt psychiatric referral (Table 2). They usually surface early in the disease course and tend to persist. Other sensory hallucinations also can occur.

The hallucinations often are detailed and vivid and the patient may be aware they are occurring, especially if the dementia is not advanced. Treatment might not be necessary for mild hallucinations, which can concern the caregiver more than the patient.

Antipsychotics paradoxically worsen hallucinations in Lewy body dementia, and many patients present to psychiatrists after failing an empiric trial. A failed antipsychotic course in a patient diagnosed with Alzheimer’s dementia could indicate that the diagnosis is incorrect.

Fluctuating cognition occurs in 50% to 75% of Lewy body cases. Alertness, attention, and concentration are variable and can cycle within hours to weeks. The patient often is fairly interactive and social for a time, then has periods of diminished function and being “out of it.” Some patients have recurrent delirium and undergo multiple workups in search of a cause.

EPS. As many as 75% of Lewy body patients have parkinsonian motor features.4 Because these features are not essential to the diagnosis, their absence is the most common reason Lewy body dementia goes unrecognized.1

Motor involvement varies and can be worsened by antipsychotics. Overuse of antipsychotics in Alzheimer’s or vascular dementia also can cause motor symptoms that mimic Lewy body features.

EPS orientation tends to be axial, showing less facial expressivity and more postural imbalance. Peripheral signs such as tremor and extremity rigidity tend to be less dominant.

MAKING THE DIAGNOSIS

Vascular and Lewy body dementia diagnoses are primarily based on clinical features and findings. Memory loss is necessary for either diagnosis.

Vascular dementia. Most consensus criteria require presence of dementia, physical or radiologic signs of a stroke, and a temporal relationship between the stroke and the dementia for a vascular dementia diagnosis.

Hachinski’s “ischemia scale” can help differentiate multi-infarct from Alzheimer’s dementia.5 Cases are scored on a 0-to-9 scale, with point values for abrupt onset; stepwise course; history of stroke; and presence of somatic complaints, emotional lability, hypertension, and focal neurologic signs. A score ≥4 suggests vascular dementia.

The scale, however, does not account for imaging studies, vascular risk factors other than hypertension, or repeated silent strokes that can cause symptoms. Also, some patients who score below the cutoff have strategic infarct dementias.

Lewy body dementia. Clinical consensus guidelines developed by McKeith et al6 can help clinicians recognize and categorize this dementia type (Table 2). Several studies of diagnostic criteria have shown very good specificity but variable sensitivity.7 Because no standard imaging modalities or serum markers exist, presence of progressive memory loss, fluctuating cognition, visual hallucinations, and EPS should drive the diagnosis.

Lewy body dementia is commonly misdiagnosed as Parkinson’s dementia. The two types are readily differentiated by onset of memory loss, which emerges late in Parkinson’s dementia but is early and prominent in Lewy body dementia.

CASE CONTINUED: HISTORY LEADS TO DIAGNOSIS

Ms. Z was diagnosed as having Lewy body dementia, as her cognitive decline clearly preceded her motor deficits. Further questioning revealed fluctuating attention levels and a history of visual hallucinations.

TESTING PATIENT FUNCTION

Neuropsychiatric tests. DSM-IV recommends testing memory, orientation, language, praxis, constructional ability, and executive control function in patients with dementia. Numerous tests can aid in diagnosis, but they generally are too lengthy to be practical. The MMSE takes 5 to 10 minutes, but it might miss mild memory loss or executive dysfunction.

Giving a quick clock-drawing test in tandem with the MMSE can help measure basic executive control and constructional ability. Also, patients with Lewy body or vascular dementia often are more proficient than patients with Alzheimer’s dementia on verbal memory tests but less proficient on visuospatial performance. Consider referring clinically challenging patients for more-extensive neuropsychiatric testing.

Lab tests. Blood tests including TSH and B12/folate screens are usually performed but rarely positive. Rapid plasma reagin testing for syphilis is no longer recommended unless syphilis is suspected.

Table 3

Potential cognitive side effects associated with psychotropic classes*

Drug class

Potential cognitive side effects

Antidepressants Tricyclics, SSRIs, SNRIs

Confusion, sedation, falls

Antihistamines

Confusion, sedation, dizziness

Antipsychotics

Sedation, fatigue, anxiety

Antispasmodics

Confusion, sedation

Benzodiazepines

Sedation, confusion, ataxia, depression

Opioids

Sedation, confusion, dizziness

Sleep-promoting agents

Amnesia, confusion, ataxia

* Not all agents in each class are associated with listed side effects

SSRIs: Selective serotonin reuptake inhibitors

SNRIs: Serotonin-norepinephrine reuptake inhibitors

Radiologic imaging. Radiologic imaging (MRI or CT) can show infarcts in vascular dementia and can rule out:

  • a brain tumor
  • a subdural hemorrhage after recent head trauma
  • or normal-pressure hydrocephalus in patients with dementia, gait instability, and/or urinary incontinence.

Brain imaging in Lewy body dementia can show hippocampal preservation8 but is not specific and does not significantly support the diagnosis. Specialized tests such as single-photon emission computed tomography or positron-emission tomography show occipital hypoperfusion9 but are expensive, not sufficiently specific, and do not add substantial value over clinical criteria.

MANAGING SYMPTOMS

Medication may be necessary if the patient is frequently and significantly agitated. Consider prescribing a selective serotonin reuptake inhibitor, an anticonvulsant such as divalproex or carbamazepine as a mood stabilizer, or a short-acting benzodiazepine. Start low and titrate slowly if needed.

Continued...
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