What is the role of language batteries and neuropsychological testing in the diagnosis of frontotemporal dementia (FTD)?

Updated: Jun 14, 2018
  • Author: Howard S Kirshner, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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Answer

Other than brain imaging studies, the most specific tests for evaluating frontotemporal lobe dementia (FTD) are evaluation with standardized language batteries and neuropsychological testing. [68, 69] Such studies assess the specific pattern of language abnormality and the presence of other cognitive and memory deficits. Preservation of many of these functions distinguishes FTD and primary progressive aphasia (PPA) syndromes from Alzheimer disease.

In distinguishing FTD from Alzheimer disease, the involvement of specific cognitive functions is the most important differentiating factor.

Grossman pointed to a double dissociation between immediate and short-term memory in a comparison study of 4 patients with PPA versus 25 patients with presumed Alzheimer disease. [69] Immediate memory was more impaired in PPA patients, whereas short-term memory deficits characterized the deficits of patients with Alzheimer disease. The frontal cortex, especially on the left side, is thought to be the site of working or immediate memory, whereas the hippocampus and other medial temporal structures, often affected early in Alzheimer disease, represent the site of short-term memory.

Other cognitive functions also showed differences between the 2 groups. Patients with PPA were more deficient than patients with Alzheimer disease on tasks of syntactic and speech fluency, correlating with the aphasia, and they had more severe impairment of attention (eg, digit span), another measure of immediate memory. Patients with PPA showed preserved memory and visuospatial functions, whereas those with Alzheimer disease were almost invariably impaired in these functions.

Atypical cases of Alzheimer disease can present with 3 “focal” syndromes: (1) aphasia, especially logopenic PPA, (2) a frontal syndrome resembling behavioral variant FTD, or (3)a visual-predominant form called posterior cortical atrophy. This issue of focal versus more generalized dementia, of course, harkens back to Pick’s original discussion of how neurodegenerative diseases progress.

Recent evidence supports neuron-to-neuron transmission of pathology in both Alzheimer disease and FTD, involving transmission of the abnormal misfolded proteins of tau or beta-amyloid from neuron to neuron in a way reminiscent of the prion diseases like Creutzfeldt-Jakob disease. [70] In other words, what eventually becomes a diffuse neurodegenerative disease has to start somewhere in the brain; it can start in one region of the brain and then spread, neuron to neuron, into unaffected areas.

PPA is a syndrome, not a pathological diagnosis. Although the term initially implied a pathology other than Alzheimer disease, we must now consider that some cases may have a syndrome of PPA but a pathological diagnosis of Alzheimer disease, or vice versa.

For example, in a series of 100 patients with focal presentations of dementing illness, 34 had autopsy-proved Alzheimer disease. [71] These cases comprised 12 (44.1%) of 26, patients with progressive nonfluent aphasia (PNFA). In comparison, only 2 (7.1%) of 28 of the behavioral-variant FTD patients and 2 (10%) of 20 with semantic dementia had postmortem evidence of Alzheimer disease.

Xiong and colleagues, [72] in a series of 33 autopsy studied cases of PNFA, 13 had Alzheimer disease pathology and 20 had FTD pathology. Four clinical features were useful in predicting FTD pathology: (1) age of onset before 60 years, (2) “sweet tooth”, or preference for sweet foods, (3) disinhibited behaviors, and (4) the presence of “knife-edge” atrophy in the frontal and/or temporal lobes. These features were only weakly predictive individually, but a majority of the FTD cases had at least one of the features, whereas most Alzheimer disease cases had none. Features that did not distinguish FTD and Alzheimer disease included progression to generalized dementia within 2 years (the defining characteristic in Mesulam’s original definition of PPA), presence of memory deficits (the usual presenting symptom in Alzheimer disease), or impairment of activities of daily living. In addition, onset before age 65 years did not distinguish cases of FTD and Alzheimer disease in thisseries, though the series had disproportionately young patients because of the authors’ interest in early dementia.

Hu and colleagues [73] reported 19 patients with PNFA and 19 with logopenic progressive aphasia. Twelve of the 19 logopenic progressive aphasia patients and 6 of 19 PNFA patients had either autopsy confirmation or CSF biomarkers suggestive of Alzheimer disease. Naming was more impaired in the Alzheimer disease patients, whereas letter-based fluency was more impaired in the non–Alzheimer disease cases.


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