Citations

Frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) are considered separate diseases; yet, they can overlap (FTLD‐MND), affecting predominantly lower motor neurons. We reviewed all cases of FTLD‐MND (N=25) to determine if lower MND is a consistent feature. We identified 2 cases (8%) with pure upper MND or primary lateral sclerosis (PLS). Detailed neuropathological examination was conducted. Case 1: a 63‐year‐old man with 7‐years of executive dysfunction, aphasia, and choking. Family history was negative. Neurological examination 1‐year prior to death revealed spasticity and extensor plantar responses, without extrapyramidal or lower MND signs. Case 2: a 69‐year‐old man with 6‐years of expressive aphasia and apraxia. Family history was negative. Neurological examination 4‐years prior to death reveled asymmetric ideomotor apraxia and parkinsonism, but no signs of upper or lower MND. Brain weights were 1140 and 930 grams, respectively. Histological examination revealed neuronal loss and gliosis of motor cortex, severe in case 1 and mild‐to‐moderate in case 2, as well as neuronal loss and gliosis in frontotemporal and parietal (case 2 only) neocortices. Activated microglial and myelin stains revealed corticospinal tract destruction to the level of the medullary pyramids. The hypoglossal nuclei were preserved. Neither ubiquitin nor TDP‐43 immunohistochemistry identified intraneuronal inclusions. Case 1 also had features of tangle dominant dementia. FTLD with pure upper MND or PLS is rare, but does exist. Unlike in typical FTLD‐MND were disease duration is 2‐3 years, those with FTLD‐PLS seem to have longer illness duration and, hence, better prognosis. Further genetic studies are needed to determine if FTLD‐PLS is a variant of FTLD‐MND or a separate disease entity.

Background: Transactive response DNA-binding protein of 43 kDa (TDP-43) is associated with hippocampal atrophy in Alzheimer’s disease (AD), but whether the association is modified by other factors is unknown. Objective: To evaluate whether the associations between TDP-43 and hippocampal volume and atrophy rate are affected by age, gender, apolipoprotein E ( APOE) ɛ4, Lewy bodies (LBs), amyloid-β (Aβ), or Braak neurofibrillary tangle (NFT) stage. Methods: In this longitudinal neuroimaging-clinicopathological study of 468 cases with AD neuropathological changes (Aβ-positive) that had completed antemortem head MRI, we investigated how age, gender, APOE ɛ4, presence of LBs, Aβ, TDP-43, and Braak NFT stages are associated with hippocampal volumes and rates of atrophy over time. We included field strength in the models since our cohort included 1.5T and 3T scans. We then determined whether the associations between hippocampal atrophy and TDP-43 are modified by these factors using mixed effects models. Results: Older age, female gender, APOE ɛ4, higher field strength, higher TDP-43, and Braak NFT stages were associated with smaller hippocampi. Rate of atrophy was greater with higher TDP-43 and Braak NFT stage, but lower in older patients. The association of TDP-43 with greater rate of atrophy was enhanced in APOE ɛ4 carriers ( p = 0.04). Conclusion: Neurodegenerative effects of TDP-43 seem to be independent of most factors except perhaps APOE in cases with AD neuropathological changes. TDP-43 and tau appear to behave independently of one another.

AbstractIntroductionFrontotemporal dementia disorders (FTDs) are heterogeneous phenotypical behavioral and language disorders usually associated with frontal and/or temporal lobe degeneration. We investigated their incidence in a population‐based cohort.MethodsUsing a records‐linkage system, we identified all patients with a diagnostic code for dementia in Olmsted County, MN, 1995–2010, and confirmed the diagnosis of FTD. A behavioral neurologist verified the clinical diagnosis and determined phenotypes.ResultsWe identified 35 FTDs cases. Overall, the incidence of FTDs was 4.3/100,000/year (95% CI: 2.9, 5.7). Incidence was higher in men (6.3/100,000, 95% CI 3.6, 9.0) than women (2.9/100,000; 95% CI: 1.3, 4.5); we observed an increased trend over time (B = 0.83, 95% CI: 0.54, 1.11, P < .001). At autopsy, clinical diagnosis was confirmed in eight (72.7%) cases.DiscussionWe observed an increased incidence and trends of FTDs over time. This may reflect a better recognition by clinicians and improvement of clinical criteria and diagnostic tools.

Purpose The primary aim was to examine the utility of the Western Aphasia Battery–Revised (WAB-R; Kertesz, 2007 ) for classifying variants of primary progressive aphasia (PPA). Traditional WAB-R metrics of Aphasia Quotient (AQ), subtest scores, WAB-R classification, and several novel metrics were examined. A secondary aim was to examine these same WAB-R metrics in individuals with primary progressive apraxia of speech (PPAOS). Method A retrospective analysis of WAB-R records from 169 participants enrolled in a study of neurodegenerative speech and language disorders was conducted. PPA/PPAOS classification was determined by consensus review of speech, language, and cognitive profiles. Scores on each of the WAB-R subtests were obtained to derive AQ, WAB-R aphasia profile, and 3 ratios reflecting relative performance on subtests. Results Mean AQ was significantly higher in the PPAOS group compared to all PPA variants except primary fluent aphasia. AQ above the normal cutoff was observed for 20% of participants with PPA. Significant main effects of group were noted for each of the subtests. Follow-up comparisons most frequently discriminated PPAOS, primary agrammatic aphasia (PAA), and logopenic progressive aphasia. Primary fluent aphasia and semantic dementia (SD) subtest scores were less distinctive, with the exception of Naming for SD, which was significantly lower than for PAA and PPAOS. When the WAB-R AQ detected aphasia, a classification of anomic aphasia was most frequently observed; this pattern held true for each of the PPA variants. The mean Information Content:Naming ratio was highest for SD, and the mean Comprehension:Fluency ratio was highest for PAA. Conclusions In the current study, AQ underestimated the presence of PPA and WAB-R classification did not distinguish among PPA classification determined by consensus. Performance on individual subtests and relative performance across subtests demonstrated inconsistent alignment with PPA classification. We conclude the WAB-R in isolation is inadequate to detect or characterize PPA. We instead suggest utilizing the WAB-R as 1 component of a comprehensive language and motor speech assessment when PPA is suspected.