A recent article in JAMA, Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia examined patient level data for 2914 participants with normal cognition, 697 with subjective cognitive impairment (SCI,) and 3972 with mild cognitive impairment (MCI) aged 18 to 100 years from 55 studies.

Normal cognition was defined as normal scores on cognitive tests, the absence of cognitive complaints for which medical help was sought, or both. Subjective cognitive impairment was defined as presence of a cognitive complaint with presentation
at a health care facility but normal cognition on tests. Mild cognitive impairment was defined according to published criteria. These include a decline in memory or another cognitive domain reported by the patient, informant, or both and objectively verified by neuropsychological testing, in combination with no or minimal impairment in activities of daily living and not meeting criteria for dementia.
at a health care facility but normal cognition on tests. Mild cognitive impairment was defined according to published criteria. These include a decline in memory or another cognitive domain reported by the patient, informant, or both and objectively verified by neuropsychological testing, in combination with no or minimal impairment in activities of daily living and not meeting criteria for dementia.
This article presents an interesting meta-analysis of patients without dementia under evaluation for cerebral amyloid pathology. A point of specific relevance, at least to me, is the complexity of stratifying patients with normal cognition and subjective cognition from patients that would progress to Alzheimer's Disease or pathological states. It seems to confirm the diffuse clinical changes in senescence as not mutually distinct from patients "diagnosed" or suspected of Alzheimer's Disease.
Accuracy in determining the cause of cognitive loss and subsequent dementia and eliminating false-positive cases in clinical trials evaluating amyloid-related therapeutics require a precise determination of the status of amyloid pathology. Further, therapy for AD requires initiation of treatment in the predementia phase when the neuropathology is limited and regeneration can potentially occur.--Editorial | Roger N. Rosenberg, MDDefining Amyloid Pathology in Persons With and Without Dementia Syndromes Making the Right Diagnosis
The prevalence of amyloid pathology increased from age 50 to 90 years from 10% to 44% among participants with normal cognition; from 12% among patients with SCI; and from 27%to 71% among patients with MCI. APOE-ε4 (see figure below) carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age where 15% of participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.
The observation that a substantial number of patients with MCI were not amyloid positive, even at older age,
suggests that the MCI phenotype does not always have AD as underlying pathology. Possible non-AD causes in MCI may be hippocampal sclerosis, mild depression, or vascular damage. Age was a risk factor for amyloid positivity, which is in line with the finding that age is an important risk factor for postmortem amyloid load and for AD-type dementia, as also shown in Figure 4A (above). The prevalence of amyloid positivity in participants with normal cognition aged 50 to 60 years was somewhat higher than found in an earlier population based
study that was not included in our analysis.
A second study, Prevalence of Amyloid PET Positivity in Dementia Syndromes A Meta-analysis, sought to clarify the clinical utility of amyloid imaging as diagnostic of AD dementia across a variety of dementia syndromes. The data from the literature report findings of patients with amyloid plaques in the absence of dementia or cognitive dysfunction so understanding the demographics and characteristics at the patient level are relevant and critical for defining prevention and disease management strategies.
Although these studies present large populations for analyses, clinical diagnosis of specific dementia type, age, and APOE status are important considerations when relying on biomarkers or amyloid PET scans to render a definitive diagnosis or detect pathology distinct from the aging brain.

Conference coverage available for Alzheimer’s Association International Conference July 18-23, 2015 in Washington DC. I will be attending the AAIC and will have an opportunity to offer limited coverage of presentations and late breaking news. Don’t miss the latest study results (embargoed until after the conference), theories, and discoveries contributing to advances in the science of dementia. Bonny@alzheimersdiseasethebrand.com.