Table 1.

Tests showing sensitivity to subtle cognitive changes associated with biomarker evidence of preclinical Alzheimer’s disease

Test	Memory component	Validation
Memory Capacity Test [13]	Verbal associative binding	34 HC, decrements in second-list learning associated with amyloid burden
Face Name Associative Memory Exam (FNAME) [22,31]	Cross-model associative binding	45 HC, decrements in face name versus face occupation associated with amyloid burden
		210 HC, good test–retest and discriminate validity for name, occupation and summary scores, useful across all educational strata
		129 HC, FNAME performance summary scores were associated with reduced hippocampal volume and APOE4 carrier status
Short-Term Memory Binding test [41]	Visual recognition, change detection, feature binding	30 asymptomatic carriers with E280A mutation showed impairment in visual short-term memory binding, suggesting short-term memory binding may be a preclinical marker for familial AD
Behavioral Pattern Separation-Object test [49,50]	Visual recognition, pattern separation	31 HC, impairments in pattern separation were noted in those with weaker RAVLT Delayed Recall Scores. Recognition Memory was normal. In 23 aMCI individuals, pattern separation deficits improved in those exposed to drug treatment during a clinical trial
Spatial Pattern Separation task [51,56]	Visual recognition, pattern separation, spatial discrimination	37 HC, Spatial Pattern Separation performance was associated with reduced bilateral hippocampal volume and with the CSF Aβ42/pTau181 ratio. Paragraph recall was not sensitive to these biomarker correlates
Discrimination and Transfer task [62,63]	Spatial discrimination	37 HC, reduced transfer performance was associated with mild-to-moderate hippocampal atrophy in CN and associated with clinical impairment 2 years later. Performance also correlated with CSF Aβ42 and the Aβ42/pTau181 ratio
Dual tasking task [76,77]	Spatial discrimination	39 E280A mutation carriers showed dual tasking impairments despite normal performances on other standard neuropsychological tests of cognition and memory. Dual tasking performance discriminates asymptomatic carriers with familial AD from healthy controls

Aβ, amyloid beta; AD, Alzheimer’s disease; aMCI, amnestic mild cognitive impairment; APOE4, apolipoprotein E4; CN, cognitively normal; CSF, cerebrospinal fluid; HC, healthy older controls; RAVLT, Rey auditory verbal learning test.