Intraindividual Variability as a Marker of Cognitive Aging: Genetic and Modifiable Risk Factors in CATSLife2’s TEDS, CAP and LTS

Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) are neurodegenerative disorders typically characterized by progressive declines in episodic memory, working memory, and/or other executive functions. Declines may be apparent up to 20 years before the condition reaches full severity (Alzheimer's Association, 2025). Given this early onset, recognizing subtle manifestations may allow for preventative behavioral changes such as diet, physical activity, and social engagement (Santiago & Potashkin, 2023). A potential measure that has been identified as a possible noninvasive marker of neurodegeneration and an early marker of dementia risk is intraindividual cognitive variability (IIV), defined as the fluctuation in a person's cognitive performance on neuropsychological tests within a single testing session (Fonseca et al., 2022). IIV can be further operationalized into two primary ways: dispersion and inconsistency. Dispersion reflects within-person variability across different tasks or cognitive domains (Hultsch & MacDonald, 2004). Dispersion captures the unevenness in performance in a cognitive profile and has been shown to have high sensitivity across age (Christiansen et al., 1999). In contrast, inconsistency represents within-person variability across repeated trials of the same task (Hultsch et al., 2002). This is often measured using reaction times or accuracy-based paradigms (Tractenberg & Pietrzak, 2011). While dispersion and inconsistency have been linked to aging and dementia risk, less is known about how these forms of variability manifest across genetically informative cohorts or how they interact with modifiable risk factors for cognitive decline, such as attentional control (i.e., distractibility) in performing processing speed and working memory tasks. Attentional stability is thought to influence the degree of moment-to-moment fluctuation in cognitive performance, suggesting a mechanistic role for distractibility in producing IIV (Chang et al., 2023; Lenartowicz et al., 2013). Accounting for individual differences in attentional stability, therefore, allows for a more precise interpretation of IIV as a potential marker for aging and dementia related cognitive vulnerability (Reynolds et al., 2019). Twin and adoption models, like those used in Twins Early Development Study (TEDS) and Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife2), provide a unique framework for distinguishing genetic and environmental contributions to cognitive performance. Therefore, the main aim of this project is to conduct a twin and sibling analysis of inconsistency and dispersion across five online cognitive tasks in TEDS and CATSLife2 cohorts. We will also examine if there is a moderating effect of sex, SES, education, and distractibility/attentional control. In addition, we will assess the association of polygenic risk scores for cognitive abilities, attention, AD/ADRD risk, as well as APOE (ε4 dosage) with IIV.