Don't forget non-Alzheimer dementias
ABSTRACTDementia is commonly encountered in the elderly, with prevalence increasing with age. Although Alzheimer disease is the most recognized form of dementia, other types have distinct clinical features and are often overlooked. Proper identification aids patients, caregivers, and physicians in planning and management.
KEY POINTS
- Vascular dementia presents as a sudden, stepwise progression of cognitive deficits.
- Lewy body dementia often involves prominent visual hallucinations.
- Progressive supranuclear palsy starts with gait and balance problems caused by downward-gaze palsy.
- Many neurodegenerative conditions involve parkinsonism, but unlike Parkinson disease, they do not tend to respond well to levodopa, and dementia develops early.
- Corticobasal degeneration involves markedly asymmetric parkinsonism.
- Frontotemporal dementia involves dramatic behavior changes, including inappropriate impulsivity and complete apathy.
- Patients with rapidly progressive dementia should be evaluated for a treatable condition such as antibody-mediated encephalitis.
CORTICOBASAL DEGENERATION
Corticobasal degeneration is a progressive, asymmetric movement disorder often manifesting initially with cognitive or behavioral impairment. It is associated with abnormality of the cytoskeleton protein tau. Onset is usually after age 60.
Asymmetric movement disorder with cognitive dysfunction
This diagnosis is clinical. Diagnostic criteria proposed in 2003 include the following core features34:
- Insidious onset and progressive course
- No identifiable cause
- Cortical dysfunction with at least one of the following: apraxia, alien limb phenomenon (one limb moves involuntarily with complex movements, eg, grabbing the other hand), cortical sensory loss, visual hemineglect, nonfluent aphasia
- Extrapyramidal dysfunction: focal rigidity unresponsive to levodopa, asymmetric dystonia.
An international consortium has developed more specific clinical research criteria for probable and possible corticobasal degeneration.35 In a series of 147 patients, the following clinical features were found: parkinsonism (100%), higher cortical dysfunction (93%), dyspraxia (82%), gait disorder (80%), unilateral limb dystonia (71%), tremor (55%), and dementia (25%).36
Behavioral problems commonly include depression; apathy, irritability, and agitation are also reported.37
Cognitive testing may reveal deficits in frontal-parietal cognitive domains including attention and concentration, executive function, verbal fluency, and visuospatial skills.38 Learning disabilities may be improved with verbal cueing (in contrast to Alzheimer disease). Patients may also have impaired graphesthesia (the ability to recognize writing on the skin only by the sensation of touch).39,40
Motor examination may reveal marked asymmetry. Hand, limb, speech, and gait apraxias are common. Gait is typically slow, with short steps and shuffling, and a wide-based or freezing gait. Arm swing may be absent on one side.
Asymmetric cortical atrophy
Early on, MRI may be normal. As the disease progresses, asymmetric cortical atrophy may be seen, especially in the posterior frontal and parietal lobes.
Levodopa ineffective in corticobasal degeneration
Corticobasal degeneration responds poorly to levodopa. Botulinum toxin has been used to help with dystonia and limb pain.
MULTIPLE SYSTEM ATROPHY
Multiple system atrophy is another atypical parkinsonian disorder, most often diagnosed in men over age 60. It is characterized by sporadic parkinsonism, cerebellar signs (involving balance and coordination), pyramidal tract dysfunction, and autonomic insufficiency in varying combinations. Two major subtypes are recognized, depending on whether the predominating presenting features are cerebellar signs or parkinsonism. In contrast to dementia with Lewy bodies, psychiatric symptoms are not a major feature, except possibly depression.41
Diagnosis requires a sporadic progressive disorder that has features of autonomic failure and poor response of parkinsonism or cerebellar ataxia to levodopa.42
Multiple system atrophy is usually not associated with dementia in the early stages, but patients develop deficits in learning, recognition, memory, and verbal fluency as the disease progresses.43 Rapid-eye-movement sleep behavior disorder has been reported in more than half of patients.44
A neurologic examination provides clues
Parkinsonian features are usually symmetric, in contrast to idiopathic Parkinson disease. These signs may include akinesia with rigidity, postural instability, hypokinetic speech, and tremor.
Cerebellar signs include nystagmus and dysarthria (speech disturbance), and gait and limb ataxia.
Pyramidal features include extensor plantar responses and hyperreflexia.
Autonomic dysfunction includes orthostatic hypotension, bladder and rectal atony, loss of sweating, urinary or fecal incontinence, and erectile dysfunction.
Electromyography may demonstrate decreased anal sphincter tone.
MRI shows atrophy of putamen and pons
Brain MRI may show atrophy of the putamen (hypointensity of the putamen with a hyperintense rim). Pons atrophy may also be present, revealing a “hot cross bun” sign in axial images. These combined findings have specificity above 90% but limited sensitivity. These signs are useful to distinguish multiple system atrophy from Parkinson dementia, but their absence does not exclude the diagnosis of multiple system atrophy.45,46
Multiple system atrophy typically responds poorly to levodopa
Levodopa may improve movement and rigidity, but many respond poorly to treatment or lose response after a few years. Fludrocortisone (Florinef) or vasoconstrictors such as midodrine (Orvaten, Proamatine) may help with orthostatic hypotension.47,48
PARKINSON DISEASE DEMENTIA
Dementia eventually develops in most patients with Parkinson disease. Older age and the akinetic rigid form of the disease are associated with higher risk. Diagnosis of idiopathic Parkinson disease before the development of dementia is essential for the diagnosis.
The Movement Disorder Society Task Force has developed new diagnostic criteria.49 Deficits must be present in at least two of the four core cognitive domains (attention, memory, executive, and visuospatial functions) and must be severe enough to affect daily functioning.
Behavioral symptoms such as affective changes, hallucinations, and apathy are common.
MRI shows characteristic brain atrophy in Parkinson disease dementia
MRI shows reduced gray matter volume in the frontal lobe in patients with Parkinson disease without dementia compared with controls. In Parkinson disease dementia, reduced volume extends to temporal, occipital, and subcortical areas. No significant volumetric differences have been observed in Parkinson dementia compared with dementia with Lewy bodies.50 A greater decrease of glucose metabolism has been found in the inferior parietal and occipital lobes in Parkinson disease dementia than in Parkinson disease without dementia.51
Rivastigmine effective for dementia
A Cochrane review supports the use of acetylcholinesterase inhibitors in patients with Parkinson disease dementia, with a positive impact on global assessment, cognitive function, behavioral disturbance, and activities of daily living rating scales.19 At this time, rivastigmine is the only FDA-approved cholinesterase inhibitor for treating Parkinson disease dementia. In clinical trials, memantine did not improve global clinical status or behavioral symptoms of dementia of Parkinson disease.51
