Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (80 page)
Authors: Mary A. Williamson Mt(ascp) Phd,L. Michael Snyder Md
Clinical Presentation
FTD appears to be associated with genetic abnormalities more frequently than AD, the symptoms progress more rapidly, and FTD patients are less likely to demonstrate memory loss on initial examination.
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Three variants of FTD are based on the functional aspects of the frontal lobe. These include a behavioral variant, several progressive aphasia variants, and semantic dementia. A smaller group of patients will also have motor impairment.
Recent genetic abnormalities have been identified that are associated with FTD. These include mutations in the MAPT gene on chromosome 17 that encodes the tau protein (tau protein repeats are found in the deposition of Pick bodies) and an abnormal form of TARDBP called pathologic TDP43, which is the major disease protein in ubiquitin-positive, tau-, and alpha-synuclein–negative frontotemporal dementia.
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The diagnosis is primarily made by clinical assessment, neuropsychologic testing, and neuroimaging with MRI. Laboratory tests to rule out treatable forms of dementia (B
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, thyroid, syphilis, electrolytes) should be considered. There is no definitive test for diagnosis of FTD, but genetic testing for some known mutations is now available. Caution should be taken in interpretation of negative tests since not all mutations underlying FTD have been identified.
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References
1. Snowden JS, Neary D, Mann DM. Frontotemporal dementia.
Br J Psychiatry.
2002;180: 140–143.
2. Rosen HJ, Hartikainen KM, Jagust W, et al. Utility of clinical criteria in differentiating frontotemporal lobar degeneration from Alzheimer disease.
Neurology.
2002;58:1608.
3. Hardy J, Parastoo M, Bryan JT. Frontal temporal dementia: dissecting the aetiology and pathogenesis.
Brain.
2006;26(4):830–831.
4. Goldman JS, Rademakers R, Huey ED, et al. An algorithm for genetic testing of frontotemporal lobar degeneration.
Neurology.
2011;76:475.
DEMENTIA WITH LEWY BODIES
Dementia with Lewy bodies (DLB) is a degenerative dementia that also presents with at least two of the following three clinical features: cognitive fluctuations, visual hallucinations, or parkinsonism.
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In contrast to AD, DLB presents early on with alterations in attention, visual, and executive functions and only later with memory deficits. It is characterized by cortical atrophy with less hippocampal atrophy than that seen in AD and by the presence of Lewy bodies, clumps of alpha-synuclein, and ubiquitin protein in neurons of the cortex, on autopsy (see eBook Figure 4-7). DLB is not thought to be a familial disorder; however, recent association with the PARK11 gene has been described.
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Diagnosis of DLB is made by clinical assessment, neuropsychologic testing, neuroimaging (MRI), and screening laboratory studies to rule out treatable forms of dementia (B
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, thyroid, syphilis, electrolytes). No specific test for definitive diagnosis of DLB is available. EEG may be helpful to rule out seizure or Creutzfeldt-Jakob disease. Genetic testing is not currently recommended.
References
1. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.
Neurology.
2005;65:1863.
2. Bogaerts V, Engelborghs S, Kumar-Singh S, et al. A novel locus for dementia with Lewy bodies: a clinically and genetically heterogeneous disorder.
Brain.
2007;130(9):2277.
PARKINSON DISEASE DEMENTIA
Parkinson disease (PD) when severe may present with dementia as a symptom surpassing the functional effects of the motor features (see also Disorders of Movement) and is then classified as Parkinson disease dementia.
The differential diagnosis from Alzheimer disease and other degenerative dementias is made by a history of motor dysfunction predating the dementia in PD. Dementia in PD may be as high as 41%, and therefore, differentiation from other dementias should be undertaken for proper treatment.
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In addition, Parkinson disease may coexist with Alzheimer disease or vascular dementia as all three are fairly common. Research continues to determine if Parkinson disease dementia and dementia with Lewy bodies may represent different presentations of the same disease.
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The risks for dementia in PD include an older age of onset, longer duration, and severity of parkinsonism. Genetic risk factors have been described; these include mutations on chromosome 1P in the ATPase gene, which is associated with juvenile parkinsonism with dementia
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; multiplication-type mutations of the alpha-synuclein gene; APOE ε4 and APOE ε2
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; and the microtubule-associated protein tau (MAPT) H1/H1 gene, which has been implicated in more rapid onset of dementia.
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The diagnosis of PD dementia is primarily made by clinical assessment and history. Dementia usually occurs in the setting of well-established parkinsonism, while in DLB, dementia may occur at the same time as the development of motor signs, and in AD, motor symptoms only develop very late in the course of disease
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. Neuropsychiatric testing may assist in the diagnosis, but no published clinical criteria for PD dementia exist. Neuroimaging with MRI may reveal more atrophy with dementia than in PD without dementia but is not diagnostic
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. Lab tests should be performed to exclude other treatable causes of dementia (CBC, electrolytes, glucose, thyroid studies, and renal and liver functions). The diagnosis of PD dementia is suggested when dementia occurs at least 1 year after the development of established parkinsonism.