Preserved cerebellar functions despite structural degeneration in older adults
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eLife Assessment
This important study examined age-related changes in cerebellar function by testing a large sample of younger and older adults, including 30 over 80 years old, on motor and cognitive tasks linked to the cerebellum and conducting structural imaging. Their findings show that cerebellar-dependent functions are mostly maintained or even enhanced across the lifespan, with cerebellar-mediated motor abilities remaining intact despite degeneration, in contrast to non-cerebellar measures. Overall, the authors provide solid evidence in support of preserved cerebellar function with age. These results highlight the resilience and redundancy of cerebellar circuits and offer key insights into aging and motor behavior.
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Abstract
Aging is frequently perceived negatively due to its association with the decline of various brain and bodily functions. While it is evident that motor abilities deteriorate with age, it is incorrect to assume that all aspects of movement execution are equally affected. The cerebellum, a brain region that is closely involved in motor control among other functions, undergoes clear structural changes with aging. While several studies suggest that cerebellar degeneration causes age-related motor control deficits, other studies suggest that the cerebellum might act as a motor reserve and compensate for its structural degeneration, leaving cerebellar motor function intact despite cerebellar degeneration. The present study aims at thoroughly investigating the impact of age on cerebellar function across an array of tasks and domains.
We investigated cerebellar motor and cognitive functions across the lifespan by examining 50 young adults (20–35 years), 80 older adults (55–70 years), and 30 older-old adults (>80 years). Participants completed a test battery comprising seven motor control tasks and one cognitive task, each designed to probe cerebellar function through different paradigms. This multi-task approach allowed for a comprehensive evaluation of performance patterns, providing a balanced perspective on cerebellar function across the different age groups. In addition, we analyzed outcomes from the same tasks that, while related to movement, were not specifically linked to cerebellar function. Structural magnetic resonance imaging was also conducted to assess whether cerebellar atrophy was present in the older and older-old groups compared to the young.
Our results revealed that, despite age-related cerebellar degeneration, cerebellar functions in older adults remained intact compared to young adults, even in adults above 80 years old. In contrast, the sensorimotor measures that were not directly linked to cerebellar function exhibited a clear pattern of decline in older adults, and were further deteriorated in the older-old adults compared to the older adults.
These findings indicate that cerebellar motor control functions remain largely preserved with age, providing compelling evidence that the cerebellum possesses a remarkable degree of functional resilience and redundancy. This suggests that cerebellar circuits may be uniquely equipped to preserve function despite structural degeneration.
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eLife Assessment
This important study examined age-related changes in cerebellar function by testing a large sample of younger and older adults, including 30 over 80 years old, on motor and cognitive tasks linked to the cerebellum and conducting structural imaging. Their findings show that cerebellar-dependent functions are mostly maintained or even enhanced across the lifespan, with cerebellar-mediated motor abilities remaining intact despite degeneration, in contrast to non-cerebellar measures. Overall, the authors provide solid evidence in support of preserved cerebellar function with age. These results highlight the resilience and redundancy of cerebellar circuits and offer key insights into aging and motor behavior.
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Reviewer #1 (Public review):
Summary:
Witte et al. examined whether canonical behavioral functions attributed to the cerebellum decline with age. To test this, they recruited younger, old, and older-old adults in a comprehensive battery of tasks previously identified as cerebellar-dependent in the literature. Remarkably, they found that cerebellar function is largely preserved across the lifespan-and in some cases even enhanced. Structural imaging confirmed that their older adult cohort was representative in terms of both cerebellar gray- and white-matter volume. Overall, this is an important study with strong theoretical implications and convincing evidence supporting the motor reserve hypothesis, demonstrating that cerebellar-dependent measures remain largely intact with aging.
Strengths:
(1) Relatively large sample size.
(2) Most …
Reviewer #1 (Public review):
Summary:
Witte et al. examined whether canonical behavioral functions attributed to the cerebellum decline with age. To test this, they recruited younger, old, and older-old adults in a comprehensive battery of tasks previously identified as cerebellar-dependent in the literature. Remarkably, they found that cerebellar function is largely preserved across the lifespan-and in some cases even enhanced. Structural imaging confirmed that their older adult cohort was representative in terms of both cerebellar gray- and white-matter volume. Overall, this is an important study with strong theoretical implications and convincing evidence supporting the motor reserve hypothesis, demonstrating that cerebellar-dependent measures remain largely intact with aging.
Strengths:
(1) Relatively large sample size.
(2) Most comprehensive behavioral battery to date assessing cerebellar-dependent behavior.
(3) Structural MRI confirmation of age-related decline in cerebellar gray and white matter, ensuring representativeness of the sample.
Weaknesses:
(1) Although the authors note this was outside the study's scope, the absence of a voxel-based morphometry (VBM) analysis limits anatomical and functional specificity. Such an analysis would clarify which functions are cerebellar-dependent rather than solely inferring this from prior neuropsychological literature.
(2) As acknowledged in the Discussion, task classification (cerebellar-dependent vs. general measures) remains somewhat ambiguous. Some "general" measures may still rely on cerebellar processes based on the paper's own criteria - for example, tasks in which individuals with cerebellar degeneration show impairments.
(3) Cerebellar-dependent and general measures may inherently differ in measurement noise, potentially biasing results toward detecting effects in general measures but not in cerebellar-dependent ones.
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Reviewer #2 (Public review):
Summary:
The authors are investigating cerebellar-mediated motor behaviors in a large sample of adults, including 30 individuals over the age of 80 (a great strength of this work). They employed a large battery of motor tasks that are tied to cerebellar function, in addition to a cognitive task and motor tasks that are more general. They also evaluated cerebellar structure. Across their behavioral metrics, they found that even with cerebellar degeneration, cerebellar-mediated motor behavior remained intact relative to young adults. However, this was not the case for measures not directly tied to cerebellar function. The authors suggest that these functions are preserved and speak to the resiliency and redundancy of function in the cerebellum. They also speculate that cerebellar circuits may be especially …
Reviewer #2 (Public review):
Summary:
The authors are investigating cerebellar-mediated motor behaviors in a large sample of adults, including 30 individuals over the age of 80 (a great strength of this work). They employed a large battery of motor tasks that are tied to cerebellar function, in addition to a cognitive task and motor tasks that are more general. They also evaluated cerebellar structure. Across their behavioral metrics, they found that even with cerebellar degeneration, cerebellar-mediated motor behavior remained intact relative to young adults. However, this was not the case for measures not directly tied to cerebellar function. The authors suggest that these functions are preserved and speak to the resiliency and redundancy of function in the cerebellum. They also speculate that cerebellar circuits may be especially good for preserving function in the face of structural change. The tasks are described very well, and their implementation is also well-done with consideration for rigor in the data collection and processing. The inclusion of Bayesian estimates is also particularly useful, given the theoretically important lack of age differences reported. This work is methodologically rigorous with respect to the behavior, and certainly thought-provoking.
Strengths:
The methodological rigor, inclusion of Bayesian statistics, and the larger sample of individuals over the age of 80 in particular are all great strengths of this work. Further, as noted in the text, the fact that all participants completed the full testing battery is of great benefit.
Weaknesses:
The suggestion of cerebellar reserve, given that at the group level there is a lack of difference for cerebellar-specific behavioral components, could be more robustly tested. That is, the authors suggest that this is a reserve given that the volume of cerebellar gray matter is smaller in the two older groups, though behavior is preserved. This implies volume and behavior are seemingly dissociated. However, there is seemingly a great deal of behavioral variability within each group and likewise with respect to cerebellar volume. Is poorer behavior associated with smaller volume? If so, this would still suggest that volume and behavior are linked, but rather than being age that is critical, it is volume. On the flip side, a lack of associations between behavior and volume would be quite compelling with respect to reserve. More generally, as explicated in the recommendations, there are analyses that could be conducted that, in my opinion, would more robustly support their arguments given the data that they have available. This is a well-executed and thought-provoking investigation, but there is also room for a bit more discussion.
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