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- Skoglund, Lena, et al.
(författare)
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Novel Progranulin Mutation Detected in 2 Patients With FTLD
- 2011
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Ingår i: Alzheimer Disease and Associated Disorders. - : Lippincott Williams & Wilkins. - 0893-0341 .- 1546-4156. ; 25:2, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions, and linkage to chromosome 17 was recently found to be caused by mutations in the progranulin (PGRN) gene. In this study, we screened a group of 51 FTLD patients for PGRN mutations and identified a novel exon 6 splice donor site deletion (IVS6+5_8delGTGA) in 2 unrelated patients. This mutation displayed an altered splicing pattern generating 2 aberrant transcripts and causing frameshifts of the coding sequence, premature termination codons, and a near absence of PGRN mRNA from the mutated alleles most likely through nonsense-mediated decay. The subsequent PGRN haploinsufficiency is consistent with previously described PGRN mutations. We present a molecular characterization of the IVS6+5_8delGTGA mutation and also describe clinical and neuropathologic features from the 2 patients carrying this PGRN mutation. From the screening of these 51 FTLD patients, we could also identify the earlier reported mutation Gln130fs, and several coding sequence variants that are most likely nonpathogenic.
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- Wattmo, Carina, et al.
(författare)
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Long-term Outcome and Prediction Models of Activities of Daily Living in Alzheimer Disease With Cholinesterase Inhibitor Treatment.
- 2011
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Ingår i: Alzheimer Disease and Associated Disorders. - 1546-4156. ; 25:1, s. 63-72
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Tidskriftsartikel (refereegranskat)abstract
- In untreated patients with Alzheimer disease (AD) the functional ability is gradually lost. What happens to the patients after continuous long-term cholinesterase inhibitor (ChEI) treatment is less investigated. The objective of this study was to describe the longitudinal functional outcome and analyze factors affecting the outcome in ChEI-treated patients. In an open, 3-year, nonrandomized, prospective, multicenter study in a routine clinical setting, 790 patients were treated with either donepezil, rivastigmine, or galantamine. At baseline and every 6 months, they were assessed with several rating scales including Instrumental Activities of Daily Living (IADL), Physical Self-Maintenance Scale (PSMS), and Mini-Mental State Examination (MMSE). A faster functional decline was associated with lower cognitive ability at baseline, older age, and the interaction of higher education and longer time in the study. The patients residing with a spouse or relative showed slower deterioration in IADL score. A higher mean dose of ChEI, regardless of drug agent, was also related to slower instrumental ADL decline. Prediction models for longitudinal functional outcome were provided. AD severity at baseline is a key factor in obtaining reliable clinical prognoses of the long-term ADL ability. The dosage of ChEI treatment could possibly lead to a different functional outcome.
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