Handgrip strength predicts longitudinal changes in clock drawing test performance. An observational study in a sample of older non-demented adults

Abstract

Objective

Impairment of physical performance might identify older people at higher risk of dementia over time. The present study evaluated handgrip strength as independent predictor of cognitive decline.

Design

Observational, prospective. Follow-up duration: 11.2 ± 0.8 months.

Setting and participants

Geriatric outpatients center. 104 consecutive stroke- and dementia-free older adults (44% men, ages 80.2±5.4 years).

Methods

The Clinical Dementia Rating scale and the Clock Drawing Test (CDT) were administered. Handgrip strength was assessed using a Jamar hand dynamometer. Brain magnetic resonance imaging studies at 1.5 T were performed. White matter damage was expressed as severity of white matter hyperintensities (WMHs). Longitudinal changes in cognitive function were expressed as 1-year decline in CDT performance.

Results

A robust association was observed between baseline handgrip strength and 1-year cognitive decline after multiple adjustment. Of note, the strength of such association was only minimally attenuated after adjusting for deep WMHs extent (β coefficient for handgrip strength = 0.183, SE= 0.038, p= 0.007, R2= 0.58).

Conclusions

Handgrip strength predicted accelerated 1-year decline in cognitive function, assessed by CDT, in a sample of older adults. Future studies are needed to elucidate the causal mechanisms linking limitations in physical function with dementia risk.

Introduction

Impairment in physical performance, e.g. gait abnormalities, might predict dementia risk over time (1). However, assessment of physical performance in geriatric practice is difficult, as it depends on examiner's expertise and there are no standardized criteria. Reduced performance of the hand and arm function identify older people with functional disability (2). Handgrip strength, a proxy of skeletal muscle strength, can be easily and inexpensively estimated in older people (3).

The prospective relationship of reduced handgrip strength to cognitive decline or dementia risk over time has been assessed by former studies (2, 4., 5., 6.). Mechanisms underlying such association are not completely understood. Subclinical brain vascular injury, e.g. leukoaraiosis, might be a risk factor for both cognitive and physical decline. To the best of our knowledge, no study has explored the extent to which brain subcortical damage mediates such relationship.

The present study aimed to evaluate handgrip strength as a predictor of longitudinal changes in cognitive function in older non-demented subjects, controlling for a range of potentially confounding variables.

Methods

Participants were selected from among older individuals referred to our ambulatory clinic for a comprehensive geriatric assessment, consisting of evaluation of disability in performing Activities of Daily Living (ADL), comorbidities and dementia screening.

Exclusion criteria were: dementia, defined by DSM-IV-TR criteria (7) and/or by scoring greater than 0.5 on the Clinical Dementia Rating scale (CDR) (8); relevant functional disability in performing ADLs, defined by scoring below 50/100 on the Barthel Index (9); osteoarthritis of the hands; neuropathy; Parkinson's disease; other forms of tremor; chorea; contraindications for brain magnetic resonance imaging assessment. Of note, handgrip test was not administered to persons with systolic blood pressure ≥180 mmHg and/or diastolic ≥110 mmHg. In order to minimize the probability of including malnourished subjects, we excluded those with a body mass index below 21 kg/m2. We also excluded subjects with history or evidence of brain large vessels infarct, coronary heart disease or arrhythmias, due to the strong association between such conditions with both prevalent and incident cognitive impairment. Written informed consent to the study was required.

Out of 115 eligible subjects, 104 completed the longitudinal assessment. Experienced staff carried out data collection, anthropometric measurements, physical and neuropsychological assessments. Brain magnetic resonance imaging studies (GE-Horizon, GE-Healthcare, Milan, Italy) were performed at 1.5 T in basal conditions using a head coil. Scans were examined by a radiologist, blinded to the clinical characteristics of the subjects, and read for periventricular and deep white matter hyperintensities (WMHs). WMHs were focal hyperintensities on proton-density and T2-weighted sequences. Periventricular WMHs were lesions abutting the lateral ventricles at the level of frontal and occipital horns and laterally. Deep WMHs were lesions not communicating with ventricles. WMHs were rated according to the method of Fazekas (10). Deep WMHs were rated as absent (score=0), punctate (=1), nearly-coalescent (=2) or confluent (=4). Periventricular WMHs were rated as absent (=0), pencil-thin lines (=1), caps/bands (=2) or confluent (=3). Both deep and periventricular WMHs were then categorized into absent/slight (=0-1), moderate (=2) or severe (=3).

Participants were administered the Clock Drawing Test (CDT), whose details are described elsewhere. Performance was rated using the Sunderland's method (11). The score ranges from 0 to 10, the higher the score the better the cognitive performance. 5 points are given for numbers placed in correct position, and 5 points for accuracy of hands denoting the time 11:10.

The question “do you feel you have more problems with memory than most?” was used to identify participants with subjective memory complaints.

Handgrip test was administered by a physician, using a Jamar hand dynamometer. Participants were asked to stand up and hold the dynamometer in the dominant hand with the arm parallel to the body.2 After adequate instruction, two trials followed and the best score was used for analysis. Handgrip strength was expressed in Kg.

Follow-up and outcomes

After a minimum of 10 months, cognitive function was assessed again by administering CDT and CDR. Longitudinal changes in cognitive function were expressed as annual changes in CDT score, calculated as the difference between second and first CDT score x 12 / months of follow-up.

Statistical analysis

All analyses were performed via Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA) version 17.0 for Windows. Baseline characteristics of participants were presented as means ± SD or frequencies, as appropriate. Pearson's correlation analysis was used to evaluate univariate associations between variables. Multiple linear regression analyses were performed to detect whether handgrip strength was an independent predictor of cognitive decline, controlling for a range of potentially-confounding variables. Statistical significance was set at 2-sided p values at ≤0.05.

Results

Table 1 shows the baseline characteristics of participants. 4 participants likely progressed to dementia, as they scored 1 or higher on the CDR at the end of follow-up. As shown by Figure 1, the greater the handgrip strength at baseline the lower the 1-year CDT score loss, in both men and women. Additional univariate significant correlated of 1-year changes in CDT were age (r=-0.582, p<0.001), deep WMHs severity (r=- 0.341, p<0.001), systolic blood pressure (r=-0,439, p<0.001), baseline CDT performance (r=-0.316, p<0.001). Table 2 shows significant predictors of 1-year CDT score changes by multiple regression models. As handgrip strength was already correlated with CDT score at baseline (r=0.197, p=0.002), an interaction term between handgrip strength and baseline CDT was entered into the model. Handgrip strength was robustly associated with 1-year cognitive decline after adjustment for a range of potentially-confounding variables. Interestingly, the strength of the association was only minimally attenuated after adjusting for deep WMHs extent.

Table 1.

Baseline characteristics of the study population

Parameter	Study population
n	104
Follow-up duration (months)	11.2 ± 0.8
Men (%)	44.0
Age (years)	80.2 ± 5.4
Education (years)	6.7 ± 2.0
Current smoking (%)	9.7
Body mass index (Kg/m2)	25.8 ± 2.8
Systolic blood pressure (mmHg)	145.2 ± 15.6
Diastolic blood pressure (mmHg)	76.5 ± 10.5
Duration of hypertension (years)	12.0 ± 8.2
Deep WMHs (%)
Absent/mild	0.3
Moderate	0.5
S evere	9.2
Periventricular WMHs (%)
Absent/mild	36.0
Moderate	36.5
Severe	23.5
Clock Drawing Test (score)	7.8 ± 2.0
Cognitive complaints (%)	33.5
CDR score of 0.5 (%)	15.6
Handgrip strength (kg)
Men	32.8 ± 11.1
Women	22.2 ± 5.7
Medications (%)
Antihypertensive	92.6
Antiplatelet	56.5
Statins	26.7
Antidiabetic	9.6
1-year Clock Drawing Test change (score)	- 1.37 ± 1.45

WMHs: white matter hyperintensities. CDR: clinical dementia rating scale.

Figure 1.

Univariate associations between the handgrip strength and the annual change in Clock Drowing Test score in men and women

Table 2.

Significant predictors of longitudinal changes in cognitive function (measured as the annual change in Clock Drawing Test score) in multiple regression models

	Model 1 (R2=0.56)			Model 2 (R2=0.58)
	β	SE	p	β	SE	p
Age (years)	-0.242	0.036	0.02	-0.217	0.067	0.04
Systolic blood pressure (mmHg)	-0.336	0.052	<0.001	-0.318	0.065	<0.001
Handgrip strength (Kg)	0.190	0.031	0.001	0.183	0.038	0.007
Deep WMHs severity (0-2)	-	-	-	-0.317	0.109	<0.001

Regression models controlled for gender (male, yes vs no), education (years), body mass index (Kg/m²), diastolic blood pressure (mmHg), current smoking (yes vs no), cognitive complaints (yes vs no) and interaction term (baseline CDT score)*(handgrip strength), ß: regression coefficient; SE: standard error. WMHs: white matter hyperintensities

Discussion

Strong links between physical limitations and poorer cognition have been indicated. Authors have suggested that gait abnormalities and physical frailty might be early indicators of dementia (1), allowing for the hypothesis that evaluation of physical performance might provide important additional information to identify high-risk individuals. In clinical practice, however, assessment of physical performance is difficult to warrant, as it depends on examiner's expertise and there are no standardized criteria.

Measurement of skeletal muscle strength by handgrip test, an easily administered instrument for the upper extremity, provides useful information to identify functional limitations and to grade disability in older people (2, 3). The relationship between handgrip strength and cognition has been explored in both cross-sectional and longitudinal studies. Data from the large population-based cohorts of the EPESE and Leiden 85-plus studies have reported significant prospective associations between poorer handgrip strength and steeper decline in global cognitive function (2, 4). Furthermore, other prospective studies have indicated consistent longitudinal associations of reduced handgrip strength with higher risk of mild cognitive impairment and Alzheimer's dementia (5, 6). Authors have proposed such prospective relationship could be mostly attributable to shared brain pathology, as impairment in both cognitive function and muscle strength may reflect central nervous system changes (4, 12). In this context, chronic brain vascular injury is of particular interest. Subcortical microvascular damage, i.e. leucoaraiosis and microbleedings, are the direct consequence of the chronic exposure to cardiovascular risk factors, e.g. adverse blood pressure, diabetes, metabolic syndrome (13., 14., 15.). Subcortical microvascular disease is common in older people, as 28% of older stroke-free individuals have silent brain infarct, and up to 83% have WMHs (14). Deep white matter harbors most of cortical/subcortical and cortical/cortical projections. Disruption of such areas may result in deterioration of functions requiring adequate information integration by inter-lobar pathways, such as muscle coordination and strength and, even more, cognitive function (13, 15).

However, the causal relationship between reduced handgrip strength and cognitive decline remains unclear for two main reasons: i) a longitudinal study has reported that decline in cognitive function might precede muscle strength impairment (16); ii) currently, there is no study reporting direct evidence that cerebral pathology mediates such association.

In our study, conducted on a sample of older people free of dementia and clinical cardiovascular disease at baseline, we observed a robust prospective association between lower handgrip strength and more rapid decline in cognitive function, assessed by CDT. Interestingly, such association appeared to be not driven by white matter damage severity, expressed as deep WMHs extent.

Our results are in line with previous reports documenting that muscle weakness may predict cognitive decline over time, and that mechanisms other than cerebral vascular pathology may be responsible for such association. There might be further etiological mechanisms. Accelerated skeletal muscle wasting, namely sarcopenia, is the most important factor influencing aging-associated muscle weakness. Authors have proposed that chronic low-grade inflammation and insulin resistance, both associated with either accelerated sarcopenia and cognitive dysfunction, may account for the relationship between weakness and cognitive decline (17., 18., 19., 20., 21.). Moreover, a study conducted in both monozygotic and dyzigotic twin pairs have reported that there may be genetic factors common to handgrip strength and specific cognitive tasks, i.e. processing speed and working memory (19).

Our study has limitations. Although our study takes into account the subcortical vascular burden, the assessment method is almost coarse, as evaluation of WMHs load has been conducted using a semi-quantitative method. Furthermore, WMHs assessment by a single radiologist could increase bias risk. In addition, we only performed brain imaging at baseline. Thus we cannot ascertain whether ulterior brain damage could be responsible for the observed association.

Furthermore, cognitive decline was evaluated basing on longitudinal changes in a single cognitive test. Nevertheless CDT appeared to be suitable for our purpose, as it sensibly detects cognitive impairment, and reliably explores executive functions, which are early affected in individuals with even silent vascular brain damage.

Postponing dementia is of eminent importance for maintaining personal independency in older people (21). Assessment of muscle strength by handgrip test may provide additional information in identifying individuals at greater risk of cognitive decline over time.

Future work is necessary to elucidate etiological mechanisms and to determine whether interventions aimed at improving muscle strength may beneficially affect cognitive outcomes in older people.

Conflict of interest

All the authors declare that there is no conflict of interest in relation to the present work.

Ethical Standards

The authors declare that the present work comply with the current laws of our Country.