Going beyond the mean: Intraindividual variability of cognitive performance in prodromal and early neurodegenerative disorders

Objective: Intraindividual variability (IIV), generally defined as short-term variations in behavior, has been proposed as a sign of subtle early impairment in neurodegenerative disorders, presumably associated with the disintegration of neuronal network connectivity. We aim to provide a review of IIV as a sensitive cognitive marker in prodromal neurodegenerative disorders. Method: A narrative review focusing not only on theoretical and methodological definitions, including an overview on the neural correlates of IIV, but mainly on results from population-based and clinical-based studies on the role of IIV as a reliable predictor of mild cognitive impairment (MCI) and conversion to dementia in neurodegenerative disorders, mostly Alzheimer's and Parkinson's disease. Results: Most studies focus on MCI and Alzheimer's disease and demonstrate that IIV is a reliable cognitive marker. IIV is partly more sensitive than mean performance in the prediction of cognitive impairment or progressive deterioration and is independent of socio-demographic variables and disease mediators (e.g., genetic susceptibility). Neuroimaging data, mostly from healthy subjects, suggest a relationship between IIV and dysfunction of the default mode network, presumably mediated by white matter disintegration in frontal and parietal areas. Conclusions: IIV measures may provide valuable information about diagnosis and progression in prodromal stages of neurodegenerative disorders. Thus, further conceptual and methodological clarifications are needed to justify the inclusion of IIV as a sensible cognitive marker in routine clinical neuropsychological assessment.