{"doi":"10.1113/jp290379","title":"On the concept of ‘mild motor impairment’: A neuromotor harbinger of sarcopenia and frailty?","abstract":"The goal of this opinion is to convince readers of the importance of nomenclature and natural history in understanding the physiology of the ageing neuromotor system. We may be a century removed from the golden age of description, where the classification by general clinical signs (physiology) and postmortem pathology defined various diseases and ailments. However one glaring omission to the present day is a satisfactory nomenclature for age-associated decline in neuromotor function, which may be both distinct and inclusive of striated muscle atrophy and weakness (i.e. sarcopenia), itself a term coined only in the last couple of decades. To aid in this endeavour we posit the term ‘mild motor impairment’, which we define as a disordered timing (when to recruit motor units, i.e. activation of motor units across different motor pools) and/or activation (motor unit type and discharge duration) of motor units, contributing to deficits in a desired motor behaviour. Like mild cognitive impairment (MCI) (Langa & Levine, 2014), ‘mild motor impairment’ may be a harbinger of more serious conditions, such as sarcopenia/frailty, that contribute to morbidity and mortality. Here our goal is threefold: (i) to convince the reader of the importance of age-related ‘mild motor impairment’, which is to motor neurons (MNs) and their synaptic inputs what MCI is to hippocampal neurons and their synapses; (ii) that a neurogenic critical framework of movement decline with age is consistent with ‘mild motor impairment’ as a concept and moreover accounts for ageing deficits unrelated to joint issues or muscle weakness (e.g. dysphagia); and (iii) some testable hypotheses that lend weight to the prior points and underscore ‘mild motor impairment’ as a neurogenic manifestation of ageing. We briefly touch on the broader clinical implications for the colloquial classification of motor impairments as ‘mild motor impairment’. Dementia, including the most common form, Alzheimer's disease (AD), is primarily characterised by deficits in memory, cognitive and executive functions (Knopman et al., 2021). It has been apparent for decades that age-associated dementia and AD are associated with extensive prodromal phases (Buchman & Bennett, 2011). The pre- or early-onset disturbances exist in a continuum with many other comorbidities, such as obstructive sleep apnoea (OSA), dysphagia, sarcopenia, decreased cardiorespiratory fitness, obesity and diabetes (Andrade et al., 2018; Humbert et al., 2010; Knopman et al., 2021). Despite this breadth of physiological disturbance in ageing, the pathophysiology of dementia and AD centres on the progressive loss of neuronal synapses, which leads to subtle changes that later precipitate full-blown neuronal death and the demented brain state (Knopman et al., 2021; Selkoe, 2002). MCI may be an intermediate phase between normal ageing and full-blown dementia, and thus a symptomatic manifestation of otherwise prodromal disease (Langa & Levine, 2014). Notably in dementia and AD the correctness of executive function decision making (i.e. the appropriateness of a particular behaviour) is impaired, not necessarily the actioned behaviour (Knopman et al., 2021). In the elderly declining motor performance is readily apparent in the absence of a specific disease condition, with pathophysiological similarities in the ageing neuromotor system to that of the MCI brain. For example subtle motor behavioural dysfunctions arise contemporaneously with altered synaptic inputs onto MNs from late middle age in rodent models (Fogarty, 2025). It takes some time before altered motor functions progress to the stage where behavioural failure due to weakness (contemporaneous with MN death and striated muscle atrophy) ensues. In humans these motor dysfunctions commonly present with a wide array of comorbidities (similar to MCI, dementia and AD), including decreased cardiorespiratory fitness, obesity, diabetes, arthritis and other joint dysfunctions (Larsson et al","journal":"The Journal of Physiology","year":2025,"id":524983,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":379270,"name":"Matthew J. Fogarty","orcid":"0000-0003-0128-7042","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T02:50:16.562292Z","pmid":"41342302","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}