Rate of Muscle Contraction Is Associated With Cognition in Women, Not in Men

Abstract

Background

In older persons, lower hand grip strength is associated with poorer cognition. Little is known about how the rate of muscle contraction relates to cognition and upper extremity motor function, and sex differences are understudied.

Methods

Linear regression, adjusting for age, race, education, body mass index, appendicular lean mass, and knee pain, assessed sex-specific cross-sectional associations of peak torque, rate of torque development (RTD), and rate of velocity development (RVD) with cognition and upper extremity motor function.

Results

In men (n = 447), higher rate–adjusted peak torque and a greater RVD were associated with faster simple finger tapping speed, and a greater RVD was associated with higher nondominant pegboard performance. In women (n = 447), higher peak torque was not associated with any measures, but a greater RTD was associated with faster simple tapping speed and higher language performance, and a greater RVD was associated with higher executive function, attention, memory, and nondominant pegboard performance. In women with low isokinetic peak torque, RVD was associated with attention and memory.

Conclusions

RVD capacity may reflect neural health, especially in women with low muscle strength.

The central nervous system controls multiple aspects of muscle strength, including maximal strength and rates of muscle contraction. Both maximal strength and the rate of muscle contraction decline with aging (1, 2). The rate of muscle contraction may be a more sensitive indicator of subtle alterations in neuromuscular function compared with peak torque (3). How different aspects of muscle function relate to cognitive and motor functions in aging is not well understood. Initial work suggests that lower grip strength and knee strength are associated with poorer cognition (4–7). But conclusions are limited due to small samples, a single cognitive measure, and no assessment of the rate of muscle contraction.

One way to assess the rate of muscle contraction is to use isometric and isokinetic dynamometry and derive isometric rate of torque development (RTD) or isokinetic rate of velocity development (RVD). Differences in isometric RTD may reflect neuronal adaptations (8). For example, isometric RTD increases with an increase in efferent neural drive.

Another major limitation is that these studies did not examine sex differences. It is known that muscle function, cognition, and motor function differ by sex (9, 10). There are sex differences in specific cognitive functions and a steeper cognitive decline during normal aging in men compared with women (9). Compared with women, men have faster motor speed (10, 11), greater muscle strength, and physical performance, but also show steeper decline with aging (12). One recent study reported that in men but not women, isometric RTD is associated with lower extremity performance independent of peak torque, suggesting that women, due to their generally lower strength than men, may use alternate movement strategies that emphasize motor control (1).

Sex differences in neuronal control of movement may help inform neural mechanisms that affect movement and cognition with aging leading to sex-specific prevention strategies for age-related physical and cognitive declines. For example, there may be sex differences in benefits from explosive strength versus heavy-resistance strength training.

This study examines relationships of peak torque and two measures of rate of muscle contraction (RTD and RVD) with cognition, manual dexterity, and upper extremity motor function in clinically normal men and women aged 50 and older. We hypothesized that the rate of muscle contraction would be associated with cognition, and that sex differences in motor control would affect the relationship.

Methods

Study Population

Participants were drawn from the Baltimore Longitudinal Study of Aging (BLSA); eight hundred ninety-four clinically normal (ie free of mild cognitive impairment and Alzheimer’s disease) older participants (50% women) aged 50 and older had concurrent data on muscle function and cognition between April 2003 and May 2012. Most had concurrent motor function data by finger tapping and Purdue Pegboard Test. Diagnoses of mild cognitive impairment and Alzheimer’s disease were determined based on an adjudication conference (13–15).

At each assessment, participants provided written informed consent. The BLSA protocol was approved by the Institutional Review Board of the National Institute of Environmental Health Sciences.

Muscle Measures

Maximal lower extremity muscle strength and rate of muscle contraction were measured using a Kin-Com isokinetic dynamometer (model 125E, V3.2, Chattanooga Group, Chattanooga, TN). Isometric knee extension peak torque and peak RTD were measured at a knee angle of 120 degrees. Participants were instructed to extend their knees as hard as possible for 3 seconds with each knee for three trials. The maximal value was defined as the peak torque. Isometric RTD was calculated as the slope of the force–time relationship (1).

Isokinetic concentric knee extension peak torque was measured at an angular velocity of 180 degrees/second. The range of motion of the knee joint angle was set between 100 and 160 degrees. Participants were instructed to extend their knees as hard as possible for three trials with each knee. Signals were sampled at 100 Hz. Isokinetic RVD was calculated as the slope of the velocity–time relationship from the onset of movement to the time point that angular velocity first exceeded 178 degrees/second (Δvelocity/Δtime). Both RFD and RTD had acceptable to high reliability (16, 17).

To compare with prior findings, grip strength was also examined. Since September 2004, grip strength data were collected using a Jamar Hydraulic hand dynamometer (Patterson Medical, Warrenville, IL). Participants were instructed to squeeze the dynamometer as hard as possible for three trials with each hand. The average kilogram of force was used for analysis.

Cognition

Cognitive function was measured using a comprehensive neuropsychological battery. Global mental status was measured using Mini-Mental State Exam (MMSE) (18) in participants aged 60 and older. Cognitive domains included memory, executive function, attention, visuospatial ability, and language in standardized scores (9, 19). Measures of memory included California Verbal Learning Test immediate and long delay free recall. Measures of executive function included Trail Making Test part B and WAIS-R Digits Span Backward. Measures of attention included Trail Making Test part A and WAIS-R Digits Span forward. Measures of language included Letter and Category Fluency. Measures of visuospatial ability included card rotations and clock drawing tests. Because clock test was given to those aged 60 and older, analyses with visuospatial ability were limited to those aged 60 and older.

Manual Dexterity

Manual dexterity was measured using the Purdue Pegboard Test (since August 2005) (20), a test involves sensorimotor integration. Poor manual dexterity performance predicts future risks of neurodegenerative diseases, such as Parkinsonism and dementia (21). The average number of two trials was used for analysis. Due to a time lag between the beginning collection of Kin-Com and the start of the Pegboard test, 19.9 per cent men and 19.7 per cent women did not have concurrent pegboard data.

Upper Extremity Fine Motor Function

Upper extremity motor function was measured using a finger tapping task (since April 2004) (22), commonly used to study fine motor function. The average number of taps per second was used for analysis. Due to a time lag between the beginning collection of Kin-Com and the start of finger tapping task, 17.5 per cent men and 15 per cent women did not have concurrent tapping data.

Covariates

Covariates included age, race, years of education, body mass index (BMI), appendicular lean mass (ALM), self-reported knee pain of the leg, and physical activity (PA). ALM was measured using dual-energy x-ray absorptiometry and calculated as the sum of lean mass from left and right arms and legs. PA was measured using a self-reported questionnaire (23). Participants were categorized into four groups: exercise ≤ 30, 30–90, 90–150, and ≥150 minutes per week. 12.8 per cent men and 10.7 per cent women did not have PA data.

Handedness was measured using the Edinburgh Inventory (24) or by self-report. Handedness information was available for 442 women and 437 men. 10.2 per cent of women and 9.8 per cent of men were left-handed.

Statistical Analysis

Sex differences in age, race, years of education, and PA were examined using independent t-tests or chi-square tests. Sex differences in BMI, ALM, muscle, cognition, manual dexterity, and upper extremity motor function were examined using linear regression adjusting for age. Sex-specific correlations between peak torque and rate of muscle contraction were examined using partial correlation controlling for age, race, BMI, ALM, and knee pain.

Sex-specific cross-sectional associations of each muscle measure with cognition, manual dexterity, and upper extremity motor function measures were examined using linear regression, adjusting for age, race, education, BMI, ALM, knee pain, and PA. Because the rate of muscle contraction was a determinant of peak torque, models of isometric peak torque were additionally adjusted for isometric RTD and models of isokinetic peak torque were additionally adjusted for isokinetic RVD. An interaction term of isometric peak torque and RTD and an interaction of isokinetic peak torque and RVD were created and tested.

A sensitivity analysis was conducted restricted to right-handers. Due to knee pain and other reasons, 11.6 per cent men and 10.5 per cent women did not have isokinetic data. Analyses of isometric knee extension were repeated in those who had both isometric and isokinetic data. To understand whether relationships of muscle with cognitive, manual dexterity, and upper extremity motor function existed in young and middle-aged adults, analyses were repeated in participants younger than 50 who had concurrent data on muscle and cognition, manual dexterity, and upper extremity motor function (68 men, mean age = 41.7 ± 5.9 years; 74 women, mean age = 40.9 ± 6.7 years).

Because multiple cognitive and motor measures were examined, a Bonferroni-corrected p-value of ≤.005 (=.05/10) was used to determine statistical significance.

Results

Compared with women, men were older, less likely to be black, had more years of education, and more likely to engage exercise ≥ 150 minutes/week (Table 1). Men had higher BMI, more ALM, higher isometric and isokinetic peak torque, and greater RTD and RVD than women. Men had lower MMSE scores, worse memory, higher visuospatial ability, and worse language performance than women. There were no sex differences in executive function or attention. Men performed faster in tapping tasks and had lower pegboard performance than women (Supplementary Table 1).

Table 1.

Sample Characteristics by Sex (age ≥ 50)

	Men (n = 447)	Women (n = 447)	p-value
	Mean ± SD or n (%)
Demographics
Age, y	71.4 ± 10.5	67.0 ± 10.2	<.001
Black	101 (22.6)	149 (33.3)	<.001
Years of education	17.6 ± 2.7	17.1 ± 2.6	.001
Body mass index, kg/m2	27.4 ± 4.2	27.0 ± 5.0	.026*
Appendicular lean mass, kg	24.8 ± 3.8 (n = 435)	16.9 ± 3.4 (n = 434)	<.001*
Exercise ≥ 150 min/wk	99 (25) (n = 390)	82 (21) (n = 399)	.009
Muscle function measures
Isometric knee extension peak torque at 120°, Nm	166.6 ± 52.2	117.4 ± 36.5	<.001*
Rate of torque development, Nm/s	850.4 ± 433.7	505.5 ± 281.1	<.001*
Isokinetic concentric knee extension peak torque at 180°/s, Nm	107.3 ± 40.1 (n = 395)	72.7 ± 25.4 (n = 400)	<.001*
Rate of velocity development for concentric 180°/s, deg/s2	1459.7 ± 273.6 (n = 395)	1405.2 ± 289.7 (n = 400)	<.001*
Self-reported knee pain	14 (3.5)	31 (7.7)	.013*
Grip strength, kg	36.1 ± 9.2 (n = 393)	22.7 ± 6.0 (n = 398)	<.001*

Notes: The bold number reflects significance at p < .05.

*Age-adjusted p-value.

In both sexes, higher isometric peak torque was associated with a greater isometric RTD after adjustment (r = .57, p < .001 for both). Higher isokinetic peak torque was associated with a greater isokinetic RVD (r = .25, p < .001 for both).

In men, after adjustment, higher RTD-adjusted isometric peak torque and higher RVD-adjusted isokinetic peak torque were both associated with faster simple tapping speed, but not with other measures (Table 2, Models 1a, 2a). Isometric RTD was not associated with any motor or cognitive measures (Table 2, Model 1b). A greater isokinetic RVD was associated with faster simple tapping speed and higher nondominant hand pegboard performance (Table 2, Model 2b). No significant interaction between peak torque and RTD/RVD was found (not shown). Higher grip strength was associated with faster simple tapping speed, but not with other measures (Table 2, Model 3).

Table 2.

Cross-sectional Associations Between Each Muscle Measure of Interest and Outcome Measures of Interest in Men (Age ≥ 50; n = 447)

		MMSE (age ≥ 60)	Memory	Executive function	Attention	Visuospatial ability (age ≥ 60)	Language	Complex tapping	Simple tapping	Pegboard dominant	Pegboard nondominant
Model		Standardized β (p-value)
1a	Isometric peak torque, Nm	0.133 (.101)	−0.042 (.532)	0.130 (.029)	0.111 (.054)	0.067 (.247)	0.059 (.311)	0.173 (.024)	0.229 (<.001)	0.146 (.020)	0.139 (.036)
1b	RTD, Nm/s	0.150 (.015)	0.074 (.108)	0.027 (.515)	−0.022 (.582)	0.052 (.227)	0.017 (.673)	0.101 (.057)	0.116 (.011)	0.048 (.222)	0.078 (.067)
2a	Isokinetic peak torque, Nm (n=395)	0.064 (.391)	−0.011 (.851)	0.078 (.117)	0.039 (.426)	0.070 (.186)	0.079 (.113)	0.087 (.223)	0.183 (.003)	0.138 (.014)	0.106 (.075)
2b	RVD, deg/s2 (n = 395)	0.057 (.366)	0.090 (.079)	0.039 (.384)	0.037 (.404)	0.058 (.188)	0.095 (.031)	0.120 (.038)	0.179 (<.001)	0.050 (.248)	0.144 (.002)
3	Grip strength, kg (n = 393)	0.152 (.096)	−0.038 (.594)	0.112 (.086)	0.016 (.802)	0.113 (.094)	0.016 (.807)	0.110 (.167)	0.191 (.005)	0.092 (.128)	0.096 (.135)

Notes: MMSE = Mini-Mental State Examination; RTD = rate of torque development; RVD = rate of velocity development.

All models were adjusted for age, race, body mass index, appendicular lean mass, years of education, and self-reported knee pain. Model 1a was additionally adjusted for RTD. Model 2a was additionally adjusted for RVD. The bold number reflects significance at p ≤ .005.

In women, after adjustment, RTD-adjusted isometric peak torque or RVD-adjusted isokinetic peak torque was not associated with any cognitive or motor measures (Table 3, Models 1a, 2a). A greater isometric RTD was associated with faster simple tapping speed and higher language performance, but not with other measures (Table 3, Model 1b). A greater isokinetic RVD was associated with higher memory, executive function, attention, and nondominant hand pegboard performance (Table 3, Model 2b). There were trends suggesting an interaction between isokinetic peak torque and isokinetic RVD in associations with attention (p = .007) and memory (p = .011). Associations of isokinetic RVD with attention and memory were only significant in women with a peak torque below the median (ie 70 Nm) (p = .001 and .002, respectively) (Supplementary Figure 1; as a contrast, Supplementary Figure 2 shows no effect in men). No other interactions were found (not shown). Higher grip strength was associated with higher memory, faster simple tapping speed, and higher pegboard dominant-hand performance (Table 3, Model 3).

Table 3.

Cross-sectional Associations Between Each Muscle Measure of Interest and Outcome Measures of Interest in Women (Age ≥ 50; n = 447)

		MMSE (age ≥ 60)	Memory	Executive function	Attention	Visuospatial ability (age ≥ 60)	Language	Complex tapping	Simple tapping	Pegboard dominant	Pegboard nondominant
Model		Standardized β (p-value)
1a	Isometric peak torque, Nm	−0.006 (.944)	0.051 (.561)	−0.107 (.155)	−0.075 (.289)	0.029 (.736)	−0.030 (.703)	0.122 (.214)	0.177 (.085)	0.040 (.620)	0.049 (.568)
1b	RTD, Nm/s	0.063 (.367)	0.055 (.410)	0.106 (.068)	0.106 (.051)	0.104 (.106)	0.171 (.004)	0.181 (.013)	0.370 (<.001)	−0.006 (.918)	0.060 (.345)
2a	Isokinetic peak torque, Nm (n = 400)	0.073 (.351)	0.082 (.305)	0.073 (.279)	0.067 (.279)	0.052 (.467)	0.077 (.280)	0.009 (.920)	0.125 (.188)	0.014 (.876)	0.048 (.599)
2b	RVD, deg/s2 (n = 400)	0.074 (.086)	0.144 (.002)	0.121 (.002)	0.101 (.004)	0.069 (.081)	0.098 (.016)	0.108 (.031)	0.060 (.253)	0.065 (.115)	0.123 (.005)
3	Grip strength, kg (n = 398)	0.201 (.035)	0.300 (.002)	0.052 (.513)	0.025 (.734)	0.078 (.376)	0.148 (.080)	0.183 (.071)	0.310 (.004)	0.249 (.002)	0.229 (.008)

Note: Same as Table 2.

Results remained largely unchanged after adjustment for PA (Supplementary Tables 2 and 3) and in right-handers (not shown). Results from isometric analyses were unchanged in those who also completed isokinetic concentric knee extension (not shown). In participants younger than 50, after adjustment for age and race, there were trends toward higher RFD-adjusted peak torque being associated with faster simple tapping speed in men (standardized β = 0.400, p = .019) and a greater RVD being associated with higher attention in women (standardized β = 0.242, p = .061). In fully adjusted models, these associations were not significant (all p > .100).

Discussion

This study shows for the first time that older men and women differ in relationships of various aspects of muscle function with cognition and upper extremity motor function. In men, both maximal strength and rate of muscle contraction are related to upper extremity motor function, but not to cognition, whereas in women, the rate of muscle contraction, particularly RVD, is predominantly related to cognition but not to upper extremity motor function, especially in women with low muscle strength. The prior research examined only maximal strength, focused on either global cognition or limited cognitive domains, or did not test sex differences. This study extends prior research by examining a greater scope of elements of muscle function, by examining multiple cognitive and upper extremity motor domains, and by examining sex differences. Our results suggest that muscle function and other aspects of motor function are differentially related to cognition, reflecting aspects of neurological function. Associations of muscle function with cognitive and motor function indicate that neural mechanisms may underlie between-person differences in isometric RTD and isokinetic RVD.

Knee extension muscle strength tends to be associated with cognitive function, consistent with prior findings (4, 6, 7). In men, higher isometric knee extension muscle strength tended toward associations with higher mental status and executive function, whereas in women, higher isokinetic knee extension muscle strength tended toward associations with higher executive function and attention.

An important finding from this study is that rate of muscle contraction, especially isokinetic RVD, is predominantly associated with cognition and not with upper extremity motor function in women but not men. Prior studies support the notion that the rate of muscle contraction may be driven by central nervous system, and training-induced improvement in the rate of muscle contraction may be determined by neural adaptations (8, 25). Another major finding is that relationships of RVD with attention and memory depend on isokinetic peak torque. Consistent patterns of a greater RVD being associated with higher attention and memory are observed only in women with low muscle strength. Perhaps women with lower muscle strength are more likely to depend on central control compared with men. In women, subtle differences in the central nervous system may be more likely to lead to functional deficits than in men. It is possible that this sex-specific pattern is established earlier in life and persists in late adulthood. In participants younger than 50, we observed consistent trends toward isometric peak torque associations with motor function in men and RVD associations with attention in women. Due to an insufficient sample size of younger adults, this study was unable to determine when in adult life this phenomenon develops in women. Future research should examine these relationships across the adult lifespan.

Of cognitive domains examined, memory, executive function, attention, and language are related to the rate of muscle contraction in women. There is evidence suggesting that the central nervous system plays a vital role in “rate coding,” which modulates force production, especially when the force output is over 50 per cent of the maximal voluntary contraction. In this study, muscle function measures are obtained from a maximal voluntary contraction, which may require higher-order cortical control.

We observed relationships between muscle function and motor function in both sexes. These findings share similarities with a prior report that muscle quality is associated with finger tapping performance (26). There is strong evidence that age-related changes in the neuromuscular system, including a reduced number of motor units, impair neuromuscular transmission, decrease the number of innervated muscle fibers, and reduce fiber size in the surviving motor units. All these changes contribute to impaired motor function (27). Future longitudinal studies are needed to better understand age-related neuromuscular predictors of motor decline.

This study has novel aspects. It examines key elements of muscle function, including both muscle strength and rate of muscle contraction from both isometric and isokinetic knee extension. These measures allowed us to explore specific muscle mechanisms in relation to cognitive and motor functions. It examines multiple cognitive domains. Sex-specific relationships provide new insights into the role of sex in prevention strategies aimed at preserving cognitive and motor function in late adulthood.

This study has limitations. Participants from the BLSA tend to be healthier than the general population, which may affect the generalizability of these findings. Visuospatial ability and MMSE tests were only performed in those aged 60 and older. Some participants did not have concurrent upper extremity motor data due to time lags in testing in the BLSA. The reduced sample size for these tests may have affected statistical power. Testing for multiple comparisons is a potential limitation. With the conservative Bonferroni correction, we may also have missed some associations.

In conclusion, in usual aging among men, both maximal muscle strength and rate of muscle contraction are associated with motor functions, but not with cognition. In women, the rate of muscle contraction, especially RVD, is predominantly associated with cognition, especially in women with low muscle strength. Neural health may contribute to between-person differences in the rate of muscle contraction in older, weaker women. Perhaps weak women with slow RVD might especially benefit from targeted speed-related strength training and effects on cognition could be assessed.

Supplementary Material

Supplementary data are available at The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences online.

Funding

This research was supported by the Intramural Research Program of the National Institute on Aging (03-AG-0325).

Conflicts of Interest

None declared.