Cognitive reserve (CR) is a construct that can be used to account for individual differences in the relationship between brain status and cognitive status (Stern, 2009, Stern, 2012, Stern et al., 2022, Stern et al., 2020). Cognitive reserve can be accumulated across the lifespan from participation in cognitive, physical, and social activities, but is likely influenced by genetic factors as well. Greater CR permits individuals to better cope with (or adapt to) age-related brain changes or pathologies and thereby delay the onset of cognitive impairment and dementia. Cognitive reserve is typically assessed with convenience proxies such as education years, occupational complexity, and self-reported participation in physical and social leisure activities. Cognitive reserve can also be measured directly using functional brain imaging measures (e.g., resting-state or task-based fMRI), yet such measures are constrained by their specific methodologies (Stern et al., 2020, Stern et al., 2005) – e.g., the implementation of CR in the brain may extend beyond resting-state functional networks, or a particular brain activation pattern during a specific cognitive task.

While cross-sectional examinations of CR have consistently observed positive associations between CR proxies and cognitive performance or status (Singh-Manoux et al., 2011, Wilson et al., 2009, Zahodne et al., 2015), the results from longitudinal examinations have been mixed (Barnes et al., 2004, Berggren et al., 2018, González et al., 2013, Jin et al., 2023, Karlamangla et al., 2009, Lane et al., 2017, Scarmeas et al., 2001, Singh-Manoux et al., 2011, Verghese et al., 2006, Verghese et al., 2003, Wilson et al., 2009, Wilson et al., 2019, Zahodne et al., 2011, Zahodne et al., 2015), and many have focused on the role of one CR proxy such as education years or occupational complexity (Berggren et al., 2018, Lane et al., 2017, Wilson et al., 2009, Wilson et al., 2019, Zahodne et al., 2011, Zahodne et al., 2015). A systematic review and meta-analysis concluded that the effects of education on cognitive decline are small and insignificant in older adults (Seblova et al., 2020). Yet, a recent large-scale study found that educational attainment reliably moderated the relationship between global, lobar, and regional brain structures and cognitive decline in middle-aged and older adults (Jin et al., 2023).

The first aim of this study was to examine the relationship between CR and cognitive decline using CR proxies that not only reflect participation in cognitive (education years) activities, but also physical (number of blocks walked per day; physical activity days per week) and social (working/volunteering, living with someone) activities. We examined this in a sample of 1,079 older adults without dementia (enrolled in the LonGenity study (Gubbi et al., 2017; Zhang et al., 2020)) who had completed up to 12 annual assessments. We also explored whether the relationship between structural brain measures (hippocampal volume and frontal cortical thickness) and cognition was moderated by CR in a subset of 112 older adults who had completed one (cross-sectional) MRI assessment. Consistent with the CR framework, we hypothesized that high CR would be associated with less cognitive decline. We further explored whether CR would moderate the relationship between hippocampal volume (and frontal cortical thickness) and cognition, such that a weaker association would be observed among those with high CR than those with low CR. A stronger association between structural brain measures and cognition among those with high than low CR would be more consistent with the concept of brain maintenance or reduced age-related brain changes or pathology as a function of lifetime experiences (Stern et al., 2022, Stern et al., 2020).

The second aim of this study was to examine the relationship between the CR proxies and gait speed decline. Gait and cognition are interrelated and share neural substrates in aging and dementia (see (Clouston et al., 2013, Cohen et al., 2016, Leisman et al., 2016, Scherder et al., 2007) for reviews) – including, but not limited to the hippocampus and the prefrontal cortex (Blumen et al., 2014, Blumen et al., 2019a, Blumen et al., 2019b, Ezzati et al., 2015, Holtzer et al., 2014, Kaup et al., 2011, O’Shea et al., 2016, Rosso et al., 2013, Rosso et al., 2017, Tripathi et al., 2019). Gait decline often precedes cognitive decline, mild cognitive impairment (MCI), and dementia (Beauchet et al., 2016, Buracchio et al., 2010, Jayakody et al., 2022, Quan et al., 2017). In fact, gait speed decline starts to accelerate about 14 years prior to a MCI diagnosis in men, and about 6 years before a MCI diagnosis in women (Buracchio et al., 2010). Our own research further suggests that age-related gait speed decline proceeds at a faster rate than age-related cognitive decline (Jayakody et al., 2022).

The relationship between CR proxies and gait speed decline is relatively unknown. One study reported that age-related gait speed decline proceeds at a slower rate in those with good cognitive function (executive function and episodic memory) than those with poor cognitive function – and that this relationship is stronger among those with high CR (as assessed with pre-morbid IQ) (Holtzer et al., 2012). Another study reported that pre-morbid IQ moderates the relationship between gait speed and incident mobility impairment, such that those with slower gait and lower IQ had an increased risk for mobility impairment (O'Brien and Holtzer, 2021). To our knowledge, the relationship between CR and gait speed decline has not been directly examined or contrasted with cognitive decline in aging. We hypothesized that CR proxies would be associated with gait speed decline. Due to the physical demands of walking, we further hypothesized that our physical CR proxies (number of blocks walked per day; physical activity days per week) would be more strongly associated with age-related gait speed decline than our social (working/volunteering, living with someone) and cognitive (education years) CR proxies. Because the hippocampus and frontal cortex has been linked to gait speed and gait speed decline (Blumen et al., 2019a, Callisaya et al., 2013, Callisaya et al., 2014, Manor et al., 2012, Rosano et al., 2007, Rosano et al., 2012, Rosso et al., 2017), we also explored whether CR proxies would moderate the relationship between cross-sectional measures of hippocampal volume and frontal cortical thickness and gait speed.