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O3‐02–02: Update on the relationship between i n vivo amyloid imaging with C‐PIB and CSF Aβ42
Author(s) -
Fagan Anne M.,
Mintun Mark A.,
Shah Aarti R.,
Mach Robert H.,
Morris John C.,
Holtzman David M.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.415
Subject(s) - pittsburgh compound b , clinical dementia rating , dementia , cerebrospinal fluid , pathology , cohort , cognitive decline , medicine , neuroimaging , amyloid (mycology) , psychology , neuroscience , oncology , disease
cytokines have an important role to play in the development or progression of Alzheimers Disease (AD). However, there is also evidence to show that the production of systemic cytokines by tissue macrophages can induce cytokine synthesis within the brain. Under normal circumstances the systemic production of cytokines leads to sickness behaviour such as apathy, fatigue and appetite suppression. However, we hypothesise that problems may arise in AD where microglia are already in a primed state and in this situation the presence of a second stimulus, such as a systemic inflammatory event leads to an exacerbation of the neurodegenerative process and cognitive decline in AD subjects. Methods: We have completed a 6 month study examining the longer term consequences of peripheral pro-inflammatory cytokines on cognitive decline and the appearance of neuropsychiatric symptoms in 300 AD subjects. Patients were examined on 4 occasions 2 months apart over a 6 month period. At each visit a history was taken of the number and nature of systemic inflammatory events over the preceding 2 months; the presence of neuropsychiatric features using the Neuropsychiatric Inventory and cognitive function using the ADAS-Cog. At each time point a blood sample was taken for peripheral cytokine production and markers of inflammatory disease. Results: Systemic inflammatory events (principally infections) were associated with a three fold increase rate of cognitive decline and the emergence of sickness behaviour symptoms. Systemic inflammatory events were associated with the production of pro-inflammatory cytokines that correlated with the rate of cognitive decline and the emergence of sickness behaviour symptoms. Peripheral cytokine levels were lower in subjects taking the cholinesterase inhibitor Donepezil. Conclusions: The production of peripheral pro-inflammatory cytokines is associated with a greater rate of cognitive decline in AD subjects supporting the hypothesis that systemic inflammatory events, principally infections, are a driving force in the neurodegeneration of AD.