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Re-evaluation of clinical dementia diagnoses with PET-PIB
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objectives: There is an overlap regarding Pittsburgh Compound-B (PIB) retention in patients clinically diagnosed as Alzheimer’s disease (AD) and non-AD dementia.  The aim of the present study was to investigate whether there are any differences between PIB+ and PIB PIB- patients in a mixed cohort of patients with neurodegenerative dementia of mild severity regarding neuropsychological test performance and regional cerebral glucose metabolism measured with 18 Fluoro-2-deoxy-d-glucose (FDG) PET.

Methods: Eighteen patients clinically diagnosed as probable AD or frontotemporal dementia were examined with  PIB PET, FDG PET and neuropsychological tests and followed for 5-9 years in a clinical setting.

Results:  The PIB+ patients (7/18) had slower psychomotor speed and more impaired visual episodic memory than the PIB- patients, otherwise performance did not differ between groups. The initial clinical diagnoses were changed in one third of the patients (6/18) during follow-up.  

Conclusions: The subtle differences in neuropsychological performance, the overlap of hypometabolic patterns and clinical features between AD and non-AD dementia highlight the need of amyloid biomarkers and readiness to re-evaluate the initial diagnosis.

Keyword [en]
Alzheimer’s disease, PIB PET, Dementia with Lewy Bodies, Frontotemporal dementia, ß-amyloid, amyloid biomarker, FDG PET, neuropsychological tests, TMT A, episodic memory
National Category
Medical and Health Sciences
Research subject
Medical Science
URN: urn:nbn:se:uu:diva-196962OAI: oai:DiVA.org:uu-196962DiVA: diva2:611253
Available from: 2013-03-15 Created: 2013-03-15 Last updated: 2013-08-30
In thesis
1. Biomarkers as Monitors of Drug Effect, Diagnostic Tools and Predictors of Deterioration Rate in Alzheimer’s Disease
Open this publication in new window or tab >>Biomarkers as Monitors of Drug Effect, Diagnostic Tools and Predictors of Deterioration Rate in Alzheimer’s Disease
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Decreased amyloid-ß42 (Aß42), increased total tau (t-tau) and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) reflect histopathological core changes in the most common dementia disorder, Alzheimer’s disease (AD). They discriminate AD from healthy controls and predict conversion to AD with a relatively high accuracy. Memantine, an uncompetitive NMDA-receptor antagonist, is indicated for symptomatic treatment of AD. The first aim of this thesis was to investigate effects of memantine on CSF concentrations of Aβ42, tau and p-tau. Secondly, the aim was to explore the relation between these CSF biomarkers and retention of the amyloid biomarker Pittsburgh compound B using positron emission tomography (PIB PET), regional glucose metabolism measured with 18Fluoro-2-deoxy-d-glucose (FDG) PET and neuropsychological test performance. The third aim was to investigate their possible utility as predictors of future rate of AD dementia deterioration. All patients in the studies were recruited from the Memory Clinic, Uppsala University Hospital. In study I CSF p-tau concentrations in 11 AD patients were reduced after twelve months treatment with memantine, indicating that this compound may affect a key pathological process in AD. Results from study II showed that the concentrations of CSF Aß42 are lower in PIB+ patients than in PIB- patients, and that the PIB retention was stable during 12 months. In study III 10 patients with the diagnoses AD (6 PIB+/4 PIB-) and 8 subjects (1 PIB+/7 PIB-) with frontotemporal dementia were included. PIB+ patients had lower psychomotor speed measured by performance on the Trail Making Test A and impaired visual episodic memory compared to the PIB- patients. The initial clinical diagnoses were changed in 33% of the patients (6/18) during follow-up. Study IV is the first-ever report of an association between high CSF tau and dying in severe dementia. These 196 AD patients were followed up to nine years after baseline lumbar puncture. Moreover, CSF t-tau concentrations above median was associated with an increased risk of rapid cognitive decline (OR 3.31 (95% CI 1.53-7.16), independently of baseline functional stage. Thus, a clear association between high levels of CSF t-tau and p-tau and a more aggressive course of the disease was shown.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 65 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 881
Alzheimer's disease, biomarkers, CSF, PIB PET, amyloid-beta, tau, rapid cognitive decline, dying in severe dementia, mortality, neuropsychological tests
National Category
Research subject
Medical Science
urn:nbn:se:uu:diva-196965 (URN)978-91-554-8629-7 (ISBN)
Public defence
2013-05-16, Enghoffsalen, Ingång 50, bv, Akademiska sjukhuset, Uppsala, 13:00 (Swedish)
Available from: 2013-04-24 Created: 2013-03-15 Last updated: 2013-08-30Bibliographically approved

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Wall, Anders
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