Understanding the Link Between
Working Memory, Cognition, and Aging

This research looks at how natural movement patterns and physical activity may relate to brain health as people grow older, highlighting the potential role of resilience in supporting healthy aging. Enjoy!

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Introduction: Primitive reflexes (PRs) are brainstem-mediated automatic responses that typically disappear in early life, but may reappear in older age, which may be associated with neurodegenerative processes. But the presence of PRs in cognitively healthy adults has not yet been sufficiently explored. The relationship between PRs and cognitive functioning (COG) may be influenced by modifiable factors such as physical activity (PA) and psychological resilience. This cross-sectional observational pilot study aimed to investigate the mediating and moderating role of physical activity and resilience in the association between primitive reflexes and cognitive functioning in older adults.

Methods: A total of 30 older adults (mean age 73.4 ± 6.9 years; 80% female) living in residential care facilities were assessed. PRs were evaluated using standardized neurological protocols, COG was measured with the Mini-Mental State Examination, PA with the Global Physical Activity Questionnaire, and resilience with the Connor–Davidson Resilience Scale. Moderation and mediation models were tested using Hayes’ PROCESS macro, controlling for age and BMI.

Results: A higher number of primitive reflexes was strongly associated with lower cognitive functioning [COG (r = −0.904, p < 0.001)]. Physical activity showed a significant mediating effect in this association, indicating that more active older adults exhibited better cognitive performance despite the presence of primitive reflexes. Resilience, although correlated with both cognition and physical activity, did not show a mediating or moderating effect.

Discussion: These findings highlight primitive reflexes as potential behavioral biomarkers of cognitive aging, and underscore the importance of physical activity as a protective factor that may buffer against neurocognitive decline.

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1 Introduction

Primitive reflexes are complex, automatic movement patterns mediated by the brain stem. They develop in the third trimester of pregnancy and probably disappear in the first three quarters of life (Zafeiriou, 2004). They may reappear as symptoms of certain neurodegenerative diseases. The cessation of primitive reflex activity is associated with the maturation of neural networks, particularly those related to frontal brain structures (Isakov et al., 1984; Jolles et al., 1993). Many researchers refer to the reappearance of reflex activity as “retrogression” (de Ajuriaguerra et al., 1963; Reisberg et al., 1999). It remains an open question whether recurrent primitive reflexes are physiological companions of aging. The integrity of prefrontal networks is crucial for complex actions such as behavioral planning and the performance of tasks that rely on working memory and executive control (Miller, 2000). Since the above-mentioned brain structures are particularly sensitive to aging (Miller and Cohen, 2001), it can be assumed that age-related cognitive decline and the appearance of primitive reflexes are consequences of the increased frequency of the same oxygen-deficient areas (Schott and Rossor, 2003). Age-related cognitive decline has been linked to structural and functional alterations in the frontal and hippocampal regions, which are particularly sensitive to reductions in cerebral blood flow and oxygen metabolism. With advancing age, cerebral perfusion decreases, especially in the prefrontal cortex and subcortical white matter (Farkas and Luiten, 2001). Chronic, low-grade cerebral hypoperfusion can lead to localized oxygen deficiency and neuronal energy imbalance, impairing synaptic transmission and executive functioning (Iadecola, 2013). Because primitive reflexes are normally inhibited by intact cortico-subcortical networks—particularly those involving the frontal lobes—hypoxic or ischemic damage to these regions may reduce cortical inhibition, allowing brainstem-mediated reflexes to re-emerge. Thus, both age-related cognitive decline and the reappearance of primitive reflexes may stem from shared hypoxia-related mechanisms affecting similar cortical and subcortical areas. Based on these findings, the question arises whether the presence of primitive reflexes in healthy older adults can be associated with impairments in certain cognitive functions, such as memory and information processing speed. The vast majority of research on this topic has been cross-sectional and has involved individuals with advanced dementia. However, it can be assumed that if the presence of primitive reflexes is a direct consequence of structural changes in the aging brain, it may be an early sign or accompanying phenomenon of changes in cognitive functioning in older adults. This assumption is supported by empirical and neurobiological evidence linking the integrity of frontal–subcortical circuits with both motor inhibition and executive control. Primitive reflexes are normally suppressed by mature corticospinal and corticobulbar pathways originating from the frontal cortex. Structural and functional deterioration in these regions—such as cortical thinning, white matter degeneration, or reduced inhibitory control—has been consistently associated with both cognitive decline and the re-emergence of reflexive motor patterns in older adults (Jolles et al., 1993; Schott and Rossor, 2003; Vreeling et al., 1995). Therefore, in cognitively intact older adults, the reappearance of primitive reflexes may reflect early behavioral manifestations of subtle cortical disinhibition, which can precede measurable cognitive deficits. This interpretation aligns with longitudinal findings indicating that early disruptions in frontostriatal connectivity predict later cognitive impairment (Miller and Cohen, 2001). Altunkalem Seydi et al. (2024) identified the grasp reflex as the factor with the highest risk of developing dementia in a published study. This meta-analysis showed that the prevalence and risk of primitive reflexes are high in older patients with dementia. Therefore, primitive reflexes, especially the grasp reflex, should be carefully assessed during routine physical examinations as part of the dementia diagnostic process.

Primitive reflexes (PRs) are automatic, brainstem-mediated motor responses that are normally inhibited during early neurodevelopment as cortical control matures (Fiorentino, 2014). Their reappearance or persistence in later life indicates a decline in central inhibitory control and may reflect age-related cortical or subcortical dysfunction (Sanders and Gillig, 2011). Therefore, PRs can serve as accessible behavioral biomarkers of neurocognitive integrity. Assessment of PRs in cognitively healthy older adults allows for the identification of subtle neurobehavioral changes that may precede measurable cognitive decline.

In this context, primitive reflexes could serve as early, non-invasive behavioral indicators of functional brain aging, especially when paired with cognitive assessments such as the MMSE, which reflect frontal lobe-related functions such as attention, memory and orientation.

Based on previous studies, a consistent positive association is demonstrated between physical activity and cognitive functioning. Not only was better cognitive functioning found among more physically active people, but also there is less cognitive decline with age in the active population (Cunningham et al., 2020; Kekäläinen et al., 2023). In addition, physical activity can be associated with fewer persistent primitive reflexes, and it has a protective role against cognitive decline via its effects on primitive reflexes (Stephens-Sarlós et al., 2024, 2025).

In the present study, resilience refers to psychological resilience—an individual’s ability to adapt successfully to stress, adversity, and age-related challenges. Resilience has been identified as a key protective factor for maintaining cognitive health and functional independence in older adults (Windle, 2011; Gooding et al., 2012), and a higher level of psychological resilience is protective against cognitive impairment (Jiang et al., 2024). Therefore, we also included resilience as a potential psychosocial variable to examine whether it relates to primitive reflex activity and cognitive functioning in late life. The association between primitive reflexes and cognitive decline is well-known and well-established, but the pathophysiological and neurobiological basis is not yet fully understood. It can be assumed that further physical and mental factors have an effect on this relationship. The well-documented association between primitive reflexes (PRs) and cognitive decline is supported by clinical and neurobiological studies showing that re-emerging PRs reflect dysfunction within frontal–subcortical inhibitory circuits, which are also affected during aging and dementia. For instance, Vreeling et al. (1995) and Franssen et al. (1993) demonstrated that the frequency of grasp, snout, and palmomental reflexes increases in Alzheimer’s and vascular dementia, correlating with the severity of cognitive impairment. Jolles et al. (1993) similarly observed associations between reflex activity and cognitive aging in non-demented older adults. The pathophysiological basis refers to degenerative or ischemic alterations in cortical and subcortical structures—particularly in the prefrontal cortex, basal ganglia, and their connecting white matter tracts—that reduce inhibitory control over brainstem motor circuits. The neurobiological basis includes mechanisms such as reduced synaptic plasticity, cholinergic dysfunction, and impaired neurotransmission resulting from decreased cerebral blood flow and reduced neurotrophic support (Cotman et al., 2007; Sleiman et al., 2016). Because these neurobiological systems are influenced by modifiable factors such as physical activity, vascular health, stress, and psychological resilience, it is plausible that both physical and mental variables modulate the relationship between primitive reflex expression and cognitive decline. By examining both physical activity and psychological resilience as potential mediators or moderators of the relationship between primitive reflexes and cognitive functioning, this study aims to identify early behavioral markers of brain aging and clarify the modifiable factors that may influence this link. Thus, the present study aimed to examine the moderating/mediating effects of physical activity and resilience on the association between primitive reflexes and cognitive functioning.

2 Methods

2.1 Study design

This research was designed as a cross-sectional observational study and followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines (von Elm et al., 2008). The completed STROBE checklist is provided as a Supplementary material.

2.2 Study sample and sample size calculation

Participants were recruited from nine residential care facilities for older adults, following approval from the facilities. Eligibility criteria included being at least 60 years of age and physically able to stand and walk without assistance. Exclusion criteria included both physical conditions (e.g., untreated hypertension, cardiovascular problems, dizziness, balance disorders) and psychiatric conditions (e.g., previously diagnosed mental or behavioral disorders). All participants underwent a medical examination, provided informed consent, and signed a GDPR-compliant data management agreement. Of the 115 people who enrolled, 30 participants (80% female; mean age = 73.43 ± 6.85 years) were included in the present study because they completed all assessments and provided fully valid datasets.

The study was conducted in the 2024 Spring/Summer. The study was granted ethical approval by the Regional, Institutional Scientific and Research Ethics Committee, Széchenyi István University (No. DHK-2024/00039/2). The study fully adheres to the ethical principles of the Declaration of Helsinki, and all methods were carried out in accordance with relevant guidelines and regulations.

A priori sample size calculation was conducted using G*Power 3.1 (Faul et al., 2007, 2009) for moderation and mediation analyses. The required sample size was computed with t tests, linear multiple regression, fixed model, single regression coefficients and F tests, linear multiple regression, fixed model, R2 increase. During the estimation (two-tails), the following parameters were set: effect size f2 = 0.35 (large), alpha error probability = 0.05, Power = 0.95 (Power = 0.85/0.80), number of tested predictors (2, GPAQ and resilience) with two covariates/confounders, BMI and age, the total number of predictors = 4. Based on the results of t-tests and F tests, the required sample size is equal to 40 and 48 (28 and 35; 25 and 31), respectively. Due to the challenge of recruiting independently functioning older people over 65 years, the necessary sample size cannot be achieved only at a lower level of power, which is a limitation of the present study. The post hoc computed achieved power was equal to 0.80 and 0.88.

2.3 Measurements

2.3.1 Primitive reflexes

Primitive reflexes were assessed using standardized neurological protocols (Fiorentino, 2014; Sanders and Gillig, 2011). A total of 13 reflex responses were tested bilaterally, including Asymmetrical Tonic Neck Reflex (ATNR), Symmetrical Tonic Neck (STNR), Moro, Spinal Galant, Palmar Grasp, Babinski, Core Tendon Guard, Sucking, Tonic Labyrinthine, Babkin response, Glabellar, Post-Rotational Nystagmus (PRN), and Schilder test. Each reflex was assessed in six trials, and a reflex was classified as “present” if it was elicited in at least four trials. The scoring was confirmed by a second observer. As the primary analyses focused on the total number of primitive reflexes, individual reflexes did not demonstrate distinct statistical effects, but their distribution was consistent with previous findings in older populations (Stephens-Sarlós et al., 2025).

2.3.2 Cognitive functioning

Cognitive performance was measured using the Mini-Mental State Examination (MMSE) (Folstein et al., 2001), a widely used screening tool that assesses several areas of cognitive ability, including orientation, immediate and delayed memory, attention, language, and visual-constructive abilities. The MMSE consists of 30 questions, with a maximum score of 30, where lower scores indicate greater cognitive impairment. Despite certain limitations in diagnostic sensitivity, the MMSE remains a reliable tool for cognitive screening in older adults, particularly in community or care settings. All assessments were conducted by PhD students in Health Promotion who were trained in structured procedures for primitive reflex and cognitive functioning assessment under the supervision of a senior researcher, and scores were checked by a second observer to increase reliability.

2.3.3 Physical activity

The level of physical activity was measured with the Global Physical Activity Questionnaire (GPAQ) (World Health Organization, 2002). The GPAQ includes 16 items measuring the frequency, duration and intensity of physical activities in three settings (activity at work, travel to and from places, recreational activities), as well as sedentary behavior. The total physical activity in MET-minutes per week was calculated.

2.3.4 Resilience

Resilience was measured with the Hungarian version of the 10-item Connor–Davidson Resilience Scale (CD-RISC 10) (Connor and Davidson, 2003; Campbell-Sills et al., 2009; Járai et al., 2015). The scale assesses the ability to cope with stress and adversity positively; the total score ranges from 0 to 40, with a higher score indicating a higher level of resilience.

2.4 Statistical analysis

For descriptive statistics of the sample size, mean ± standard deviation and relative frequencies were reported. The association between the variables (primitive reflexes, PR; cognitive functioning, COG; physical activity, PA; resilience, RES) was examined using Pearson’s correlation. We tested whether the association between PR and COG is moderated or mediated by PA/RES adjusted for age and BMI (covariates/confounders, Figure 1). Moderation and mediation analyses were conducted with the Hayes’ PROCESS macro (Hayes, 2022). For simple moderation, Model 1, for simple mediation, Model 4 was used with the covariates/confounders. The level of significance was set at 0.05.