Although most cases of primary progressive aphasia (PPA) have one of the varieties of frontotemporal lobar degeneration (FTLD) as their pathological substrate, a subset shows Alzheimer's disease (AD) ...pathology. We report that all eight cases in our clinic diagnosed as possible PPA, on account of the presence of episodic memory difficulties in addition to severe language impairment at the onset of disease, showed AD pathology. Neither focal accentuation of AD pathology nor vascular lesions in language-related areas was observed. Seven of these eight patients showed large argyrophilic thorny astrocyte clusters (ATAC) in the fronto-temporo-parietal cortex and subcortical white matter. The intensely tau immunoreactive astrocytes in ATAC were morphologically similar to the perivascular, subpial, and subependymal astrocytes in elderly brains, but ATAC differ from the latter by the cortical and subcortical location, widespread distribution outside the medial temporal lobe, and intense argyrophilia. The location of ATAC was related to neither local variations in the load of AD pathology, nor the myelin density of white matter. ATAC were not seen in a comparison group of six cases of AD without a prominent aphasia syndrome. Because of the similarity of astrocytes in ATAC to those seen independently of AD pathology in several subtypes of FTLD and two reported cases of PPA we hypothesize that they are a marker of a pathological process concurrent with AD, and related to the focality of the clinical presentation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To describe language impairment in the corticobasal degeneration syndrome (CBDS) presenting as either a cognitive or motor disorder, to compare the evolution of aphasia in CBDS with primary ...progressive aphasia (PPA), and to examine whether the side of maximal cerebral atrophy or akinesia reflects the severity of aphasia.
We divided 40 patients with CBDS according to motor or cognitive onsets and conducted detailed language assessments with the Western Aphasia Battery (WAB). We analyzed scores according to the side of atrophy and motor rigidity. Longitudinal performance over three annual assessments was compared against matched patients with PPA and Alzheimer disease.
Language at baseline was more impaired in cognitive than motor-onset CBDS but there was no correlation between the side of atrophy or motor impairment and the WAB. Serial assessment (n = 19) showed a similar evolution of aphasia in cognitive-onset CBDS and PPA and delayed aphasia in motor-onset CBDS.
Aphasia is common in the corticobasal degeneration syndrome but there is little correlation with the laterality of clinical deficits. Cognitive-onset corticobasal degeneration syndrome and primary progressive aphasia are similar such that their aphasia appears identical.
Pick complex--historical introduction Kertesz, Andrew
Alzheimer disease and associated disorders,
2007 Oct-Dec, 2007-10-00, 20071001, Volume:
21, Issue:
4
Journal Article
This historical summary follows the major conceptual developments of the cohesive rather than the fractionated view of the disease, named after Pick. Clinical and biologic evidence in favor the ...entity is discussed. The changing and proliferating knowledge and terminology requires the integration of several levels of descriptions, while keeping the work in the past in sight. A historical perspective helps to prevent the chaos of terminological confusion and reinventing the wheel.
Variants in transmembrane protein 106 B (
TMEM106B
) modify the disease penetrance of frontotemporal dementia (FTD) in carriers of progranulin (
GRN
) mutations. We investigated whether TMEM106B is ...also a genetic modifier of disease in carriers of chromosome 9 open reading frame 72 (
C9ORF72
) expansions. We assessed the genotype of 325
C9ORF72
expansion carriers (cohort 1), 586 FTD patients lacking
C9ORF72
expansions with or without motor neuron disease (MND); cohort 2, and a total of 1,302 controls for
TMEM106B
variants (rs3173615 and rs1990622) using MassArray iPLEX and Taqman genotyping assays. For our primary analysis, we focused on functional variant rs3173615, and employed a recessive genotypic model. In cohort 1, patients with
C9ORF72
expansions showed a significantly reduced frequency of carriers homozygous for the minor allele as compared to controls 11.9 vs. 19.1 %, odds ratio (OR) 0.57,
p
= 0.014; same direction as carriers of
GRN
mutations. The strongest evidence was provided by FTD patients (OR 0.33,
p
= 0.009) followed by FTD/MND patients (OR 0.38,
p
= 0.017), whereas no significant difference was observed in MND patients (OR 0.85,
p
= 0.55). In cohort 2, the frequency of carriers homozygous for the minor allele was not significantly reduced in patients as compared to controls (OR 0.77,
p
= 0.079); however, a significant reduction was observed when focusing on those patients with frontotemporal lobar degeneration and TAR DNA-binding protein 43 inclusions (FTLD-TDP; OR 0.26,
p
< 0.001). Our study identifies
TMEM106B
as the first genetic factor modifying disease presentation in
C9ORF72
expansion carriers. Homozygosity for the minor allele protects carriers from developing FTD, but not from developing MND; similar effects are seen in FTLD-TDP patients with yet unknown genetic causes. These new findings show that the protective effects of
TMEM106B
are not confined to carriers of
GRN
mutations and might be relevant for prognostic testing, and as a promising therapeutic target for the entire spectrum of FTLD-TDP.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Patients with behavioural variant frontotemporal dementia demonstrate abnormalities in behaviour and social cognition, including deficits in emotion recognition. Recent studies suggest that the ...neuropeptide oxytocin is an important mediator of social behaviour, enhancing prosocial behaviours and some aspects of emotion recognition across species. The objective of this study was to assess the effects of a single dose of intranasal oxytocin on neuropsychiatric behaviours and emotion processing in patients with behavioural variant frontotemporal dementia. In a double-blind, placebo-controlled, randomized cross-over design, 20 patients with behavioural variant frontotemporal dementia received one dose of 24 IU of intranasal oxytocin or placebo and then completed emotion recognition tasks known to be affected by frontotemporal dementia and by oxytocin. Caregivers completed validated behavioural ratings at 8 h and 1 week following drug administrations. A significant improvement in scores on the Neuropsychiatric Inventory was observed on the evening of oxytocin administration compared with placebo and compared with baseline ratings. Oxytocin was also associated with reduced recognition of angry facial expressions by patients with behavioural variant frontotemporal dementia. Together these findings suggest that oxytocin is a potentially promising, novel symptomatic treatment candidate for patients with behavioural variant frontotemporal dementia and that further study of this neuropeptide in frontotemporal dementia is warranted.
This study examined the impact of various degenerative dementias on access to semantic knowledge and the status of semantic representations. Patients with semantic dementia, primary progressive ...aphasia, and Alzheimer’s disease were compared with elderly controls on tasks of category and letter fluency, with number of words generated, mean lexical frequency and errors recorded. The findings are consistent with the view that category and letter fluency rely on both common and unique cognitive processes. Fluency tasks, with the richness of data obtained, are valuable in distinguishing different dementia syndromes from one another.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background: Although semantic dementia (SD) is characterised by a multimodal loss of semantic knowledge, it has been demonstrated that lexical-semantic representations are not equally disrupted in SD ...and that some categories may be recognised better than others. Little is known, however, about the pattern of the category-specific comprehension deficits in SD and whether it differs from that of other forms of progressive aphasias.
Aims: This exploratory study aimed to investigate the evolution of category-specific deficits of single-word comprehension in progressive aphasias.
Methods & Procedures: A total of 19 patients with a clinical diagnosis of SD, 25 patients with primary progressive aphasia with agrammatic and relatively nonfluent speech (PPA), and 25 patients with Alzheimer's disease (AD) with aphasia were studied longitudinally with the Western Aphasia Battery (WAB). The Auditory Word Recognition subtest of the WAB was utilised to assess comprehension of words derived from different semantic categories.
Outcomes & Results: The analysis revealed that, over time, category-specific deficits of single-word comprehension were seen in all three groups of patients. Participants with SD as well as those with PPA and AD were impaired on both pointing to fingers and the right-left orientation task. However, patients with SD were the only group that showed defective recognition of their own body parts. Interestingly, individuals with SD had no difficulties identifying colours, letters, and numbers, even during the follow-up testing. In addition, in all three groups the extent of category-specific deficits was associated with the severity of aphasia.
Conclusions: These results indicate that category-specific deficits of single-word comprehension are frequently seen not only in patients with SD but also in individuals with PPA or AD, and that the extent of these deficits is associated with the severity of aphasia. However, the pattern of these deficits is often different in these three forms of neurodegenerative conditions and more dissociations between semantic categories are observed as each of these diseases progresses.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK, VSZLJ
To specify the presenting symptoms and clinical course of patients with frontotemporal dementia (FTD) and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion.
The 2011 discovery of the ...C9ORF72 repeat expansion causing familial FTD and amyotrophic lateral sclerosis has permitted retrospective evaluation of potential defining clinical characteristics that may distinguish carriers of the C9ORF72 mutation from other patients with FTD. Prior reports identified a subset of patients with FTD who had an unusually high prevalence of psychosis, although their specific symptoms had not yet been fully described.
From a cohort of 62 patients with FTD, we conducted a retrospective chart review of 7 patients who had C9ORF72 mutations on genetic testing, and 1 untested sibling of a C9ORF72 carrier.
Detailed histories revealed a higher prevalence of psychosis, including visual and auditory hallucinations and delusions, in the 8 C9ORF72 carriers than in our patients with sporadic FTD.
This cohort confirms and adds clinical details to the reports of a high prevalence of psychotic phenomena in patients who have C9ORF72 mutations as well as FTD or amyotrophic lateral sclerosis.
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