Objective: To investigate the relationship between age-related frailty and intra-individual variability of reaction time in normal ageing people.

Background: The neurobiological processes of normal aging and Parkinson’s disease (PD) share common features [1]. During normal aging, elevated intra-individual variability (IIV), as a marker to predict cognitive decline, is related to the dopaminergic circuit in frontal lobe [2]. Meanwhile, the declined function neuromuscular junction is common in ageing people and PD patients [3], which represented with frailty, such as handgrip strength. Considered individually, the relationship between frailty and IIV of reaction time (IIV of RT) that drive changes in normal ageing is currently unclear.

Methods: 193 community-living healthy seniors (mean age: 70.3±4.2, 56.5% female) were recruited from our previous cohort. A structured neuropsychological battery was used to assess the main domains of cognitive function, including global cognition (Montreal Cognitive Assessment Hong Kong version, HK MoCA), attention (Trail making test part A, TMT-A), executive function (Trail making test part B, TMT-B) and working memory (delayed recall). According to the criteria of Fried et al [4], frailty was evaluated by handgrip strength (in kg) using a digital dynamometer (Takei 5401 Digital Dynamometer, Japan). IIV of RT was measured using the computerized Flanker test with 288 trials with an index as intraindividual coefficient of variation of reaction time (ICV-RT) [5]. Pearson correlation coefficient was employed to test the relationship between age, frailty, and IIV of RT.

Results: Age-related cognitive decline was mainly found in executive domain (TMT-B: r=0.255, p=0.003). With gender as a covariate, advancing age was prominently correlated with weak handgrip strength (left: r=-0.355, p<0.001; right: r=-0.391, p<0.001) and elevated IIV of RT (r=0.204, p=0.018). Meanwhile, mild association was found between weak right handgrip strength and IIV of RT (r=0.195, p=0.024).

Conclusions: In the context of age-related executive function decline, the close relationship between frailty and IIV highlights the possible neurobiological link embedded in the dopamine-dependent circuits in aging brain. The results may also shed new light on the in-depth understanding of Parkinsonism and serve as ancillary indicators for evaluating the neurotherapeutic effects (i.e., brain stimulation).

References: [1] Lu, H., & Lam, L. C. (2017). Associations between intra-individual variability and Montreal Cognitive Assessment (MoCA) in cognitive ageing and prodromal dementia: A domain-specific perspective. Parkinsonism & related disorders. [2] MacDonald, S. W., Nyberg, L., & Bäckman, L. (2006). Intra-individual variability in behavior: links to brain structure, neurotransmission and neuronal activity. Trends in neurosciences, 29(8), 474-480. [3] Gonzalez-Freire, M., de Cabo, R., Studenski, S. A., & Ferrucci, L. (2014). The neuromuscular junction: aging at the crossroad between nerves and muscle. Frontiers in aging neuroscience, 6, 208. [4] Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., … & McBurnie, M. A. (2001). Frailty in older adults: evidence for a phenotype. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 56(3), 146-157. [5] Lu, H., Chan, S. S., & Lam, L. C. (2017). ‘Two-level’ measurements of processing speed as cognitive markers in the differential diagnosis of DSM-5 mild neurocognitive disorders (NCD). Scientific reports, 7(1), 521.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/relationship-between-age-related-frailty-and-intra-individual-variability-of-reaction-time-in-healthy-seniors-implications-for-parkinsons-disease/