From: Diagnosis and biomarkers of predementia in Alzheimer's disease
Clinical stage | Underlying pathological mechanisms | Putative clinical and biological markers | Potential therapeutic interventions |
---|---|---|---|
Asymptomatic (pre-clinical AD) | Intracerebral accumulation of amyloid-β | - CSF concentrations of Aβ42 | - Cognitive reserve (education and level of intellectual functioning) |
 |  | - Molecular imaging (PiB-PET) | - Lifestyle changes (nutrition, physical fitness, reduction of stress) |
 |  | - Autossomal dominant mutation(APP, PS1, PS2 genes) | - Management of underlying factors (cardiovascular risk factors, toxic and comorbid conditions) |
Prodromal (pre-dementia AD) | Aβ-related pathology(amyloid cascade) | - Episodic memory impairment(amnestic MCI) | - Anti-amyloid therapy: * immunotherapy anti-Aβ * modulation of β- and γ-secretase * anti-fibrillization agents and chelators |
 |  | - CSF concentrations of Aβ42 |  |
 |  | - Molecular imaging (PiB-PET) |  |
 |  | - Autossomal dominant mutation(APP, PS1, PS2 genes) |  |
 | Tau-related pathology (neurodegeneration) | - Multiple-domain amnestic MCI | - All above |
 |  | - CSF concentrations of Tau(total and phosphorylated Tau) | - Neuroprotective approaches(antioxidants, anti-inflammatory drugs) |
 |  | - Brain metabolism (FDG-PET) | - Tau-related therapies(GSK inhibitors, lithium) |
 |  | - Medial temporal lobe atrophy(volumetric MRI, VBM) | - Neurorestorative approaches(NGF, BDNF, stem cells) |
Clinical dementia | Neuritic plaquesNeurofibrillary tangles | - Neuropsychological tests | - Antidementia drugs (cholinesterase inhibitors, memantine) |
 |  | - Functional assessment | - Cognitive training |
 |  | - Structural imaging (CT/MRI) | - Functional rehabilitation (ADLs) |
 |  | - Neuropathology | - Psychoeducation (caregivers) |