Cognitive and motor function in MS are inherently related, and a multifaceted strategy may improve evaluation of deficits in these domains, even in early MS.

“Cognitive and motor symptoms often happen concurrently in patients with MS, and several studies have found a correlation between cognitive dysfunction and slower gait speed, poorer walking endurance, higher step length variability, and increased fall frequency,” Maria A. Rocca, MD, explains. “However, the reason for this correlation is unclear.”

There are two potential explanations for this. “First, patients with intact mobility simply tend to do better on cognitive tests than those with motor impairment, and motor and cognitive dysfunction develop in parallel without influencing each other,” she says. “Second, high-order cognitive functions play a role in coordinating and controlling mobility, especially in subjects with motor impairment, and cognitive deficits can contribute to motor dysfunction.”

According to Dr. Rocca, MS-related structural brain damage may represent “a common substrate” between both phenomena. As a result, the investigators aimed to test the impact of MS-related brain damage on the association between cognition and motor function “to demonstrate that cognitive impairment can contribute to motor dysfunction.”

For a study published in the Journal of Neurology, Dr. Rocca and colleagues enrolled 106 patients with relapsing-remitting MS (RRMS) and 81 healthy controls. All patients had a 3.0 T MRI to measure T2 lesion volumes, T1 lesion volumes, and normalized brain volumes. “We measured cognitive function with the Brief Repeatable Battery of Neuropsychological Tests, walking speed with the Timed 25-Foot Walk Test (T25FW), and hand dexterity with the Nine-Hole Peg Test (9-HPT),” Dr. Rocca notes. “To evaluate the impact of cognitive dysfunction on motor performance, we tested their association while controlling for all possible confounding factors.”

They assessed associations between demographic, clinical, cognitive, MRI, and functional measures using multivariate analyses and hierarchical linear regression.

Associations Between Cognition & Motor Performance

Among patients with RRMS, the Spatial Recall Test and the Symbol Digit Modalities Test positively correlated with the 9-HPT (P<0.001) and the T25FW (P≤0.035), while the Paced Auditory Serial Addition Test (PASAT) correlated with the 9-HPT (P≤0.009). The 9-HPT and T25FW were significantly associated with normalized brain volumes (P≤0.016), as well as T2 and T1 lesion volumes (P≤0.009). Hierarchical regression models identified age and normalized deep gray matter volume as indicators of T25FW scores (adjusted R2=0.109). Younger age, female sex, higher normalized gray matter volume, and higher PASAT 2″ scores predicted higher 9-HPT scores (adjusted R2=0.337).

“Positive correlations were found between walking speed measured with T25FW and two cognitive tests,” Dr. Rocca says. “However, higher correlation coefficients were observed between cognitive outcomes and hand dexterity than walking speed, suggesting that eye-hand coordination required to perform timely and skillful movements necessitates more cognitive resources than movement coordination needed to walk forward.”

The researchers utilized hierarchical regression analysis because “it is a technique that allows assessment of association between clinical outcomes—in this case, hand dexterity, walking speed, and cognitive tests—while controlling for possible confounding factor such as age, sex, and disease duration.”

Using this technique enabled the investigators to determine whether cognitive dysfunction contributed to motor impairment in MS. They demonstrated that worse performance on the 9-HPT, which measures hand dexterity, was associated with lower scores on PASAT 2”, a cognitive test that assesses attention and information processing speed, even after controlling for the effect of age, sex, and gray matter atrophy, she notes (Table).

Strategies for Measuring Functional & Cognitive Deficits

“The most important finding of this study is the association between hand dexterity and high-order cognitive functions even after controlling for structural brain damage,” Dr. Rocca says. “This result confirms that complex movement and cognition are inherently related to one another, and cognitive and motor symptoms do not develop in parallel in MS.”

The study provides support for the use of a multidimensional approach to enhance the evaluation of functional and cognitive deficits, even in early MS, she continues. Further, the role of neuropsychological evaluation and cognitive training programs are of “even greater importance,” given the role of cognitive dysfunction in hand-motor performance.

“A growing body of literature suggests the presence of a close relationship between cognitive and motor impairment in numerous neurological disorders,” Dr. Rocca says. “However, possible shared pathological mechanisms underlying this relationship are not well-established. Moreover, dual-task testing—or the simultaneous performance of cognitive tasks while walking—is frequently administered to evaluate functional impairments. Given the result of the study, however, the simultaneous performance of cognitive tasks while executing timely and skillful hand movements may increase the sensitivity of the test.”