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• W1815440825 abstract "Effectiveness of future treatment strategies in Alzheimer’s disease (AD) will rely on early detection of disease and the possibility to clearly evaluate their effects. The findings presented in this thesis concerns both early in vivo detection of amyloid deposition in the brains of patients at risk of developing AD and the longitudinal changes of pathological and functional parameters in patients with AD. A couple of years ago the first study with in vivo detection of amyloid using the radiotracer N-methyl [ 11 C] 2-(4 -methylaminophenyl)-6-hydroxy-benzothiazole also known as 11 C-Pittsburgh Compound B ( 11 C-PIB) with positron emission tomography (PET) was performed in collaboration between researchers in Pittsburgh, USA, Uppsala and Stockholm, Sweden. This first study showed a significant difference between AD patients and healthy controls in regards to their 11 C-PIB retention. The research presented in this thesis is both continuations and new investigations based on this initial research. Results obtained in the studies presented in this thesis showed that the amyloid deposition is an early event in the development of AD present already in patients with mild cognitive impairment (MCI) that later develop AD. We could also show that the amyloid deposition in brain was closely correlated to concentrations of pathological biomarkers in the cerebrospinal fluid (CSF) at an early stage. While functional decline with decreased cerebral metabolic rate of glucose (CMRglc) measured with 18 F-FDG PET and episodic memory tests did not show a relationship in MCI patients but did at the clinical stage of AD. Our results also suggests that the early deposition of amyloid increase to a certain level and then reaches a plateau as shown by a quite stable 11 C-PIB retention in AD patients followed for a mean period of 2.5 years. We could also show that the dynamic 11 C-PIB PET scan do not only contain information on amyloid load but also information on brain function as the early frames contain a blood flow component that is related to CMRglc. The general conclusions to be drawn from these studies are that 11 C-PIB PET shows promising results of both early detection of disease and the possibility to use it for evaluation of current and future anti-amyloid therapies. The possibility to extract functional information will further increase the usefulness of 11 C-PIB PET in AD research and clinical assessment of dementia. LIST OF PUBLICATIONS I. Henry Engler, Anton Forsberg, Ove Almkvist, Gunnar Blomquist, Emma Larsson, Irina Savitcheva, Anders Wall, Anna Ringheim, Bengt Langstrom, Agneta Nordberg. Two-year follow-up of amyloid deposition in patients with Alzheimer's disease. Brain. 2006;129:2856-2866 II. Anton Forsberg, Henry Engler, Ove Almkvist, Gunnar Blomquist, Goran Hagman, Anders Wall, Anna Ringheim, Bengt Langstrom, Agneta Nordberg. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiology of Aging. 2008;29(10):1456-1465 III. Anton Forsberg*, Henry Engler*, Bengt Langstrom, Agneta Nordberg. The use of PIB-PET as a pathological and functional marker in AD. Submitted manuscript IV. Anton Forsberg, Ove Almkvist, Henry Engler, Anders Wall, Bengt Langstrom, Agneta Nordberg. Amyloid deposition is an early event in AD showing complex relationships with CSF biomarkers and functional parameters. Submitted manuscript *shared first authorship SAMMANFATTNING PA SVENSKA Alzheimers sjukdom (AD) ar den vanligaste formen av demenssjukdomarna och drabbar ungefar 6 procent av befolkningen over 65 ars alder. Idag ar diagnostik av AD grundat pa klinisk utvardering framst genom kognitiva och neuropsykologiska test. De patologiska forandringar som karakteriserar AD ar ansamlingar av intracellulart hyperfosforylerat tau och extracellulara amyloida plack samt nedbrytning av hjarnans nervceller. Dessa forandringar i hjarnan kan idag studeras i levande patienter genom olika avbildningstekniker som magnetrontgen och positronemissionskamera (PET). PET kan anvandas kliniskt for att studera funktionella forandringar i hjarnan som forsamringar av glukosmetabolism och blodflode i hjassloben (parietallob) och tinningsloben (temporallob). Ganska nyligen utvecklades en ny molekyl for att mata de amyloida placken i hjarnan kallad 11 C-PIB. Genom 11 C-PIB-PET har det visats att det gar att separera AD-patienter fran friska kontroller (FK) baserat pa 11 C-PIB-bindningen i hjarnan. Hjarnans funktion kan studeras med PET genom att mata glukosmetabolismen (CMRglc) med molekylen 18 F-FDG. Malet med denna avhandling var att med hjalp av anvandning av PET utveckla och forbattra tidig diagnostik for Alzheimers sjukdom genom att undersoka tidiga neurofysiologiska och patologiska forandringar i hjarnan hos patienter med mild kognitiv svikt (MCI) och longitudinellt studera AD-patienter. I min forsta studie genomforde vi en uppfoljning av AD-patienter over ca tva ar med 11 C-PIB-PET och kunde da visa att 11 C-PIB-bindningen var tamligen stabil medan CMRglc i hjarnan och kognitionen fortsatte att forsamras hos patienterna. Detta kan vara ett tecken pa att amyloid-inlagringen nar en plata medan hjarnans funktion fortsatter att progressivt forsamras. I den andra studien genomforde vi PET-undersokningar av amyloid och CMRglc i MCI patienter. MCI ses som ett forstadium till AD dar ca 10-15 procent konverterar till AD under en ettarsperiod. Vi visade att 11 av 21 undersokta MCI-patienter hade forhojda varden av amyloid i hjarnan och bland dessa konverterade 7 till AD. Detta pekar pa att 11 C-PIB-PET kan vara en bra teknik for att pa ett tidigt stadium urskilja de personer som med stor sannolikhet kommer att utveckla AD. Den tredje studien undersokte mojligheten att anvanda tidiga delen av den dynamiska 11 C-PIB-PET-undersokningen som ett matt pa blodflodet i hjarnan. Vi fann att detta matt var val korrelerat till CMRglc och att dessa tva parametrar visade samma resultat i gruppjamforelser (AD, MCI, FK). Detta tyder pa att 11 C-PIB-PET skulle kunna anvandas for att fa fram bade patologisk och fysiologisk information. I den fjarde studien undersokte vi relationerna mellan amyloid och glukosmetabolism i hjarnan, samt patologiska forandringar i cerebrospinalvatskan (CSF), och episodiskt minne. Vi kunde da visa att det fanns klara skillnader i dessa relationer i olika stadier av sjukdomen dar amyloid i hjarnan var korrelerat till amyloid i CSF tidigt i sjukdomsprogressen medan funktionella matt som CMRglc i hjarnan och episodiskt minne var relaterade hos kliniskt diagnostiserade AD-patienter. Slutsatsen i denna avhandling ar att avbildningstekniken PET ar en metod som visar stor potential att, med radioliganden 11 C-PIB, kunna anvandas for tidig diagnostik av patienter med stor risk att utveckla AD, studera sjukdomsutveckling och utvardera nuvarande och kommande behandlingsstrategier." @default.
• W1815440825 created "2016-06-24" @default.
• W1815440825 creator A5055059044 @default.
• W1815440825 date "2008-09-19" @default.
• W1815440825 modified "2023-09-28" @default.
• W1815440825 title "Amyloid imaging in Alzheimer´s disease and mild cognitive impairment by Positron Emission Tomography" @default.
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