The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.

Mild cognitive impairment (MCI) was proposed as a nosological entity referring to elderly people with mild cognitive deficit but no dementia. MCI is a heterogeneous clinical entity with multiple sources of heterogeneity. The concept of MCI was reviewed and a diagnostic procedure with three different stages was proposed by the European Consortium on Alzheimer’s Disease Working Group on MCI. Firstly, MCI should correspond to cognitive complaints coming from the patients or their families; the reporting of a relative decline in cognitive functioning during the past year by a patient or informant; cognitive disorders as evidenced by clinical evaluation; absence of major repercussions on daily life; and absence of dementia. These criteria, similar to those defined during an international workshop in Stockholm, make it possible to identify an MCI syndrome, which is the first stage of the diagnostic procedure. Secondly, subtypes of MCI had to be recognised. Finally, the aetiopathogenic subtype could be identified. Identifying patients at a high risk for progression to dementia and establishing more specific and adapted therapeutic strategies at an early stage, together with more structured overall management, is made possible by the diagnostic procedure proposed.

Three sets of research criteria are available for diagnosis of Alzheimer’s disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer’s disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer’s disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer’s disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer’s disease at the mild cognitive impairment stage and progression to Alzheimer’s disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer’s disease. Their 3-year progression rate to Alzheimer’s disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer’s disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer’s disease. Their 3-year progression rate to Alzheimer’s disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer’s disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer’s disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer’s disease likelihood group. The 3-year progression rate to Alzheimer’s disease-type dementia was 59% in the high Alzheimer’s disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer’s disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer’s disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer’s disease likelihood group or the International Working Group-2 prodromal Alzheimer’s disease group could be considered.

Background/Aims: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. Methods: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer’s disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson’s disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. Results: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer’s disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson’s disease dementia. Conclusion: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.