Abstract
In view of the growing prevalence of Alzheimer's disease (AD) worldwide, there is an urgent need for the development of better diagnostic tools and more effective therapeutic interventions. At the earliest stages of AD, no significant cognitive or functional impairment is detected by conventional clinical methods. However, new technologies based on structural and functional neuroimaging, and on the biochemical analysis of cerebrospinal fluid (CSF) may reveal correlates of intracerebral pathology in individuals with mild, predementia symptoms. These putative correlates are commonly referred to as AD-related biomarkers. The relevance of the early diagnosis of AD relies on the hypothesis that pharmacological interventions with disease-modifying compounds are likely to produce clinically relevant benefits if started early enough in the continuum towards dementia. Here we review the clinical characteristics of the prodromal and transitional states from normal cognitive ageing to dementia in AD. We further address recent developments in biomarker research to support the early diagnosis and prediction of dementia, and point out the challenges and perspectives for the translation of research data into clinical practice.
Highlights
Alzheimer’s disease (AD) is the most common dementing disorder in older people
Individuals with mild cognitive deficits do display signs of AD pathology, since approximately 50% are already in Braak neurofibrillary stage III or higher, and 20% are likely to be in more advanced stages of neuropathology [108]
The development of biomarkers for AD is needed to target the severity of underlying brain pathology independently of brain reserve
Summary
Alzheimer’s disease (AD) is the most common dementing disorder in older people. As a consequence of population aging worldwide, a fourfold increase in the prevalence of AD is expected to occur over the decades. In a recent study conducted in our group, the objective assessment of functional state provided evidence that patients with MCI may have mild but significant impairment in higher-order activities of daily living, such as shopping skills and managing finances, as compared to healthy older controls [42]. In a longitudinal study with healthy older adults, changes in CSF biomarker levels associated with AD correlated with decline in cognitive functions, suggesting that these biomarkers may help identify early neurodegenerative processes of AD [105,106]. These notions have oriented recent task forces to develop diagnostic criteria for preclinical AD [107]. AD, Alzheimer’s disease; MCI, mild cognitive impairment; Ab, amyloid-beta peptide; CSF, cerebrospinal fluid; APP, amyloid precursor protein; PS, pre-senilins 1 and 2; PET, positron emission tomography; PiB, Pittsburgh compound B; FDG, fluorodeoxyglucose; CT, computerized tomography scan; MRI, magnetic resonance imaging; VBM, voxel-based morphometry
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