International Working Group (IWG) 2 Criteria for Alzheimer's Disease Diagnosis

Positive diagnosis for typical AD = selection of all criteria in Part A + ≥1 item in Part B. For other types of AD including atypical, mixed, and preclinical AD, see Dubois 2014 . Part A: Specific clinical phenotype (must have both) Early significant episodic memory impairment (isolated or associated with cognitive/behavioral changes suggesting mild cognitive impairment or dementia syndrome) that includes both of the following: Gradual progressive change in memory function for >6 months. Objective evidence of hippocampal amnestic syndrome* based on significantly impaired performance on episodic memory test with established specificity for AD, e.g. cued recall, Free and Cued Selective Reminding Test . Part B: In-vivo evidence (must have ≥1) CSF: decreased Aβ 1-42 and increased P-tau or T-tau Amyloid PET: increased tracer retention Genetic testing: AD autosomal dominant mutation in PSEN1, PSEN2, or APP genes *Hippocampal amnestic syndrome may be difficult to identify in later stages, in which case in-vivo evidence of Alzheimer’s pathology in the presence of dementia syndrome may be sufficient. Exclusion criteria** for typical AD (if any are present, diagnosis is not typical AD) History Sudden onset Early occurrence of gait disturbances, seizures, major and prevalent behavioral changes Clinical features Focal neurological features Early extrapyramidal signs Early hallucinations Cognitive fluctuations Other medical conditions severe enough to account for memory and related symptoms Non-AD dementia Major depression Cerebrovascular disease Toxic, inflammatory, and metabolic disorders, all of which may require specific investigations MRI FLAIR or T2 signal changes in the medial temporal lobe that are consistent with infectious or vascular insults **Should also exclude concomitant pathologies (e.g. vascular lesions) and other causes of cognitive disorders or dementia.