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Introduction: Clinical trials involving patients with Alzheimer’s disease (AD) continue to try to identify disease-modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. Methods: A systematic review sought research that elicited information from people with AD, their caregivers, and health-care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. Results: Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. Discussion: Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments.

BACKGROUND: Amyloid PET (aPET) imaging could improve patient outcomes in clinical practice, but the extent of impact needs quantification. OBJECTIVE: To provide an aggregated quantitative analysis of the value added by aPET in cognitively impaired subjects. METHODS: Systematic literature searches were performed in Embase and Medline until January 2017. 1,531 cases over 12 studies were included (1,142 cases over seven studies in the primary analysis where aPET was the key biomarker; the remaining cases included as defined groups in the secondary analysis). Data was abstracted by consensus among two observers and assessed for bias. Clinical utility was measured by diagnostic change, diagnostic confidence, and patient management before and after aPET. Three groups were further analyzed: control patients for whom feedback of aPET scan results was delayed; aPET Appropriate Use Criteria (AUC+) cases; and patients undergoing additional FDG/CSF testing. RESULTS: For 1,142 cases with only aPET, 31.3% of diagnoses were revised, whereas 3.2% of diagnoses changed in the delayed aPET control group (p < 0.0001). Increased diagnostic confidence following aPET was found for 62.1% of 870 patients. Management changes with aPET were found in 72.2% of 740 cases and in 55.5% of 299 cases in the control group (p < 0.0001). The diagnostic value of aPET in AUC+ patients or when FDG/CSF were additionally available did not substantially differ from the value of aPET alone in the wider population. CONCLUSIONS: Amyloid PET contributed to diagnostic revision in almost a third of cases and demonstrated value in increasing diagnostic confidence and refining management plans.

Background The performance of [18F]flutemetamol amyloid PET against histopathological standards of truth was the subject of our recent article in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (2017;9:25–34). Main body This viewpoint article addresses infrequently observed discordance between visual [18F]flutemetamol PET image readings and histopathology based solely on neuritic plaque assessment by CERAD criteria, which is resolved by assessing both neuritic and diffuse plaques and/or brain atrophy. Conclusion [18F]flutemetamol PET signal corresponds predominantly to neuritic plaque pathology but is also influenced by the presence of diffuse plaques. This could allow for detection of diffuse amyloid deposits in the early stages of AD dementia, particularly in the striatum where diffuse amyloid is most commonly observed.

Background The performance of [18F]flutemetamol amyloid PET against histopathological standards of truth was the subject of our recent article in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (2017;9:25–34). Main body This viewpoint article addresses infrequently observed discordance between visual [18F]flutemetamol PET image readings and histopathology based solely on neuritic plaque assessment by CERAD criteria, which is resolved by assessing both neuritic and diffuse plaques and/or brain atrophy. Conclusion [18F]flutemetamol PET signal corresponds predominantly to neuritic plaque pathology but is also influenced by the presence of diffuse plaques. This could allow for detection of diffuse amyloid deposits in the early stages of AD dementia, particularly in the striatum where diffuse amyloid is most commonly observed.