Premium
IC‐PL‐01: Clinical and Imaging Correlates of Brain Amyloidosis in Healthy Persons
Author(s) -
Knopman David
Publication year - 2011
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.2011.05.052
Subject(s) - dementia , amyloidosis , medicine , amyloid (mycology) , asymptomatic , appropriate use criteria , pittsburgh compound b , disease , neuroimaging , autopsy , pathology , neuroscience , psychology , psychiatry
Background: Amyloid imaging has revolutionized thinking about the pathogenesis of Alzheimer’s disease (AD), prior CSF and autopsy findings notwithstanding. High levels of brain beta-amyloid by PET imaging are seen in most patients with AD dementia and MCI patients who are likely to progress to dementia. These two facts were unsurprising. On the other hand, the observation that 20% to 40% of cognitively intact elderly persons have AD-dementia-like levels of b-amyloid by PET imaging has resulted in a fundamental change in views about AD. Conclusions: Conceptually, the finding in normal subjects means that there is a long preclinical phase of the pathophysiology of AD. B-amyloidosis itself must be at least one step removed from the proximal events that cause cognitive impairment. The implication for therapeutics is that approaches directed at b-amyloid reduction should be targeted at asymptomatic people who harbor b-amyloidosis. The implications for diagnosis are substantial. The absence of preventive therapies at present puts a damper on the use of amyloid imaging for therapeutic decisionmaking. Ignoring that inconvenient fact for the moment, the non-invasiveness of PET imaging coupled with the graphic image of abnormal levels of b-amyloid offers the unprecedented option to assess risk for future AD dementia. Risk assessment using amyloid imaging will be complicated. There are many factors that modify the relationship. Age: Brain b-amyloidosis and risk for dementia are strongly related to age. The prevalence of positive amyloid imaging scans in cognitively normal persons anticipates, by about 15 years, the prevalence curve for AD dementia, based on work by Rowe et al. Genetics: Carriers of APOE e4 allele have a higher probability of having abnormal amyloid imaging. Cognitive Reserve: Higher educational attainment, better general health or larger brain volume each might modify risk relationships, by delaying the onset of cognitive impairment. Other brain diseases: Because other diseases lead to dementia, a “negative” amyloid imaging study predicts only “No AD pathology,” not “no dementia.” Competing mortality: In the age range at issue >70 yrs old competing mortality will reduce the predictive accuracy of “positive” scans.