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Should Slowing Be Considered a Distinct Geriatric Syndrome?

  • Philip D. Sloane
    Correspondence
    Address correspondence to Philip D. Sloane, Departments of Family Medicine and Internal Medicine, School of Medicine, and the Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, 725 Martin Luther King, Jr Boulevard, CB 7590, Chapel Hill, NC 27599, USA.
    Affiliations
    Departments of Family Medicine and Internal Medicine, School of Medicine, and the Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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  • Gregg Warshaw
    Affiliations
    Departments of Internal Medicine and Family Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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      A geriatric syndrome is a clinical condition that is common in older persons. It is the result of the accumulated effects of impairments in multiple body systems; it can arise by multiple etiological pathways, and it is associated with reduced ability to manage everyday activities and challenges.
      • Inouye S.K.
      • Studenski S.
      • Tinetti M.E.
      • Kuchel G.A.
      Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept.
      ,
      • Rausch C.
      • van Zon S.K.R.
      • Liang Y.
      • et al.
      Geriatric syndromes and incident chronic health conditions among 9094 older community-dwellers: findings from the Lifelines Cohort Study.
      Often cardinal symptoms of geriatric syndromes are exaggerations of the normal changes of aging. Because of this, a geriatric syndrome may initially be difficult to diagnose. One example is the challenge to identify the transition from normal cognitive changes of aging to the geriatric syndrome of cognitive impairment.
      • Grundman M.
      • Petersen R.C.
      • Ferris S.H.
      • et al.
      Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials.
      The number of conditions labeled as geriatric syndromes has mushroomed over the past 2 decades.
      • Ahmed N.
      • Mandel R.
      • Fain M.J.
      Frailty: an emerging geriatric syndrome.
      • Cruz-Jentoft A.J.
      • Landi F.
      • Topinková E.
      • Michel J.P.
      Understanding sarcopenia as a geriatric syndrome.
      • Hassan E.B.
      • Duque G.
      Osteosarcopenia: a new geriatric syndrome.
      • Payne M.A.
      • Morley J.E.
      Dysphagia: a new geriatric syndrome.
      • Stevenson J.M.
      • Davies J.G.
      • Martin F.C.
      Medication-related harm: a geriatric syndrome.
      • Thapa S.
      • Shmerling R.H.
      • Bean J.F.
      • Cai Y.
      • Leveille S.G.
      Chronic multisite pain: evaluation of a new geriatric syndrome.
      • Tinetti M.E.
      • Williams C.S.
      • Gill T.M.
      Dizziness among older adults: a possible geriatric syndrome.
      • van der Putten G.J.
      • de Baat C.
      • De Visschere L.
      • Schols J.
      Poor oral health, a potential new geriatric syndrome.
      At this point, one could wonder whether some restraint in this labeling might be worth considering. Nevertheless, aging is by nature a multisystem process, and the scientific literature on aging-related conditions is still in a relatively early phase of development. In this context, we feel that each new claim of a possible geriatric syndrome should be evaluated based on these necessary characteristics: (1) It should be increasingly common with age and typically caused by multiple factors; (2) it should have manifestations and consequences that are clinically meaningful; (3) it should be identifiable and measurable; and (4) it should be distinct from other conditions or syndromes.
      In this issue of JAMDA, van de Schraaf et al.,
      • van de Schraaf S.A.J.
      • Rhodius-Meester H.F.M.
      • Aben L.
      • et al.
      Slowing: a vascular geriatric syndrome?.
      using analyses of 556 older persons seen in ambulatory memory clinics, propose that abnormally slow thinking, mood, and gait constitute a uniform geriatric syndrome. They suggest that it is often associated with small vessel vascular disease of the central nervous system.
      • van de Schraaf S.A.J.
      • Rhodius-Meester H.F.M.
      • Aben L.
      • et al.
      Slowing: a vascular geriatric syndrome?.
      In this editorial, we discuss the concept of slowness as a potential geriatric syndrome and suggest potential clinical implications and future research directions.

      Slowing as a Concomitant of Normal Aging

      Slowing down is a physiological reality that accompanies aging. The basal metabolic rate, an overall measure of energy consumption at rest, decreases with age, even in healthy persons.
      • Schrack J.A.
      • Knuth N.D.
      • Simonsick E.M.
      • Ferrucci L.
      “IDEAL” aging is associated with lower resting metabolic rate: the Baltimore Longitudinal Study of Aging.
      One result, among others, is the lowered body temperature commonly observed in older persons compared with younger adults.
      • Waalen J.
      • Buxbaum J.N.
      Is older colder or colder older? The association of age with body temperature in 18,630 individuals.
      Neuromuscular slowing occurs normally as well. The speed of nerve conduction within both central and peripheral nerves declines with age,
      • Dorfman L.J.
      • Bosley T.M.
      Age-related changes in peripheral and central nerve conduction in man.
      ,
      • Kommalage M.
      • Gunawardena S.
      Influence of age, gender, and sidedness on ulnar nerve conduction.
      most likely due to a variety of factors, such as demyelination and less stable neuromuscular junctions.
      • Hunter S.K.
      • Pereira H.M.
      • Keenan K.G.
      The aging neuromuscular system and motor performance.
      These combine with motor changes to cause age-related declines in speed of motor performance, including such clinically relevant milestones as gait speed.
      • Bohannon R.W.
      • Williams Andrews A.
      Normal walking speed: a descriptive meta-analysis.
      The cardiovascular system also exhibits age-related slowing. In healthy subjects, the number of seconds with which blood makes its circuit from the heart and back (circulation time) gradually increases as individuals get older. This is due to age-related linear reductions in cardiac output and stroke volume not accompanied by concomitant increases in heart rate.
      • Brandfonbrener M.
      • Landowne M.
      • Shock N.W.
      Changes in cardiac output with age.
      Another physiological issue with clear health implications is wound healing, which is well known to be slower in older versus younger persons.
      • Jones P.L.
      • Millman A.
      Wound healing and the aged patient.
      A complex process, wound healing involves multiple systems as it progresses through inflammation, proliferation, angiogenesis, and epidermal restoration.
      • Gould L.
      • Abadir P.
      • Brem H.
      • et al.
      Chronic wound repair and healing in older adults: current status and future research.
      Changes in wound healing rates, like many other clinical processes that decline with age, thus have complex physiological explanations.
      • Ashcroft G.S.
      • Horan M.A.
      • Ferguson M.W.
      Aging alters the inflammatory and endothelial cell adhesion molecule profiles during human cutaneous wound healing.
      Not all aspects of human performance slow down with age, however. Bowel transit time is longer in most segments of the large bowel, but there is no relation between age and transit time through the small intestine or rectosigmoid.
      • Bouchoucha M.
      • Fysekidis M.
      • Rompteaux P.
      • et al.
      Influence of age and body mass index on total and segmental colonic transit times in constipated subjects.
      • Fischer M.
      • Fadda H.M.
      The effect of sex and age on small intestinal transit times in humans.
      • Nandhra G.K.
      • Mark E.B.
      • Di Tanna G.L.
      • et al.
      Normative values for region-specific colonic and gastrointestinal transit times in 111 healthy volunteers using the 3D-Transit electromagnet tracking system: influence of age, gender, and body mass index.
      In the central nervous system, although there are noteworthy reductions in neural processing speed with age in normal individuals,
      • Eckert M.A.
      Slowing down: age-related neurobiological predictors of processing speed.
      some functions seem to improve. Psychologists have explained one key aspect of these changes by describing 2 types of intelligence. Fluid intelligence, characterized by speed, flexibility, and abstract reasoning, tends to be higher in younger adults. Crystallized intelligence, which depends on prior knowledge and experience, tends to be higher in older persons.
      • Horn J.L.
      • Cattell R.B.
      Age differences in fluid and crystallized intelligence.

      When Does Slowing Transition From Normal to Pathological?

      As noted previously, some decline in many areas is a common aspect of normal aging. It is possible, however, for slowness to become pathological, as exemplified by the fact that slowness is 1 of the 5 key signs of the frailty phenotype.
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • et al.
      Frailty in older adults: evidence for a phenotype.
      Furthermore, psychomotor slowness can be a risk factor for many problems in everyday living, such as by increasing one's risk of accident as a pedestrian.
      • Wilmut K.
      • Purcell C.
      Why are older adults more at risk as pedestrians? A systematic review.
      In our clinical experience, functionally relevant slowness tends to be associated with 1 or more comorbid diseases. As is the case for well-known geriatric syndromes such as cognitive impairment, recurrent falls, and urinary incontinence,
      • Zimmerman S.
      • Sloane P.D.
      JAMDA's new editors-in-chief present a vision for the Journal of Post-Acute and Long-Term Care Medicine.
      physiological slowness likely needs the added effect of 1 or more comorbid diseases to become severe enough to negatively affect daily activities. Indeed, as with so many geriatric conditions, there are likely to be multiple factors underlying pathological slowness.
      An example would be a woman in her early 80s who moves slowly through her day, to the point that her activities of daily living occupy most of her time and energy. Clinical evaluation identifies contributing factors to her slowness to include mild cognitive impairment, osteoarthritis of the hips and knees, chronic congestive heart failure, and polypharmacy.

      Should Slowness Be Considered a Geriatric Syndrome?

      Van de Schraaf et al.
      • van de Schraaf S.A.J.
      • Rhodius-Meester H.F.M.
      • Aben L.
      • et al.
      Slowing: a vascular geriatric syndrome?.
      propose that reduced gait speed, abnormally slow thought processing, and apathy are aspects of slowness often seen concomitantly, and therefore could be considered a geriatric syndrome. To address whether or not slowness should be added to the growing list of such entities, let us consider one by one the necessary components of a geriatric syndrome presented earlier in this editorial.
      Is it increasingly common with age and caused by multiple factors? As noted, many physiological features slow with aging. Often, as in the case of the woman described in the previous section, slowness is due to multiple factors. Slowness fulfills this criterion.
      Does it have manifestations and consequences that are clinically meaningful? The answer here is also affirmative. Motor slowness, such as reduced gait speed, can make it hazardous to ambulate in the community (eg, to cross a street at a traffic signal). When advanced, it can markedly slow one's ability to carry out everyday activities. such as dressing, cooking, or driving. Apathy also can be associated with adverse outcomes.
      Are there acceptable, clinically feasible measures? Here the answer is also yes, as key aspects of slowness have more reliable, readily obtainable measures than several other geriatric syndromes (eg, dizziness, falls). Gait speed is already a core measure in geriatrics, with much research and well-established norms.
      • Mehmet H.
      • Robinson S.R.
      • Yang A.W.H.
      Assessment of gait speed in older adults.
      For persons who cannot ambulate and therefore are unable to be tested using gait speed, a Moberg Picking-Up Test appears to be a valid alternative.
      • Santos-Eggimann B.
      • Ballan K.
      • Fustinoni S.
      • Büla C.
      Measuring slowness in old age: times to perform moberg picking-up and walking speed tests.
      ,
      • Meyer M.L.
      • Fustinoni S.
      • Henchoz Y.
      • et al.
      Slowness predicts mortality: a comparative analysis of walking speed and moberg picking-up tests.
      Apathy also has several measures, although they have limitations, and separation of primary apathy from dementia or depression-related apathy is challenging.
      • Esposito F.
      • Rochat L.
      • Juillerat Van der Linden A.C.
      • et al.
      Apathy in aging: are lack of interest and lack of initiative dissociable?.
      Can it be clearly differentiated from other conditions or syndromes? The answer will depend on further research and analysis. There are many other processes that can be slowed. The 3 features identified by van de Schraaf et al.
      • van de Schraaf S.A.J.
      • Rhodius-Meester H.F.M.
      • Aben L.
      • et al.
      Slowing: a vascular geriatric syndrome?.
      are a useful starting point but they may not characterize the syndrome of geriatric slowness, if it becomes a syndrome in the end. The selection of domains by van de Schraaf et al.
      • van de Schraaf S.A.J.
      • Rhodius-Meester H.F.M.
      • Aben L.
      • et al.
      Slowing: a vascular geriatric syndrome?.
      appears arbitrary and incomplete, given the wide variety of physiological functions that decline with aging. For example, increased reaction time, presbyphagia, and the speed of light/dark adaptation are examples that could equally be considered in the construct. Such uncertainty of definition and characterization is, of course, the way geriatric conditions evolve. The process of defining such entities typically takes decades. Indeed, many well-established geriatric syndromes, such as frailty and sarcopenia, while well recognized, even now lack a universally accepted definition.

      Is Vascular Disease a Necessary Component of the Pathological Slowness?

      Table 2 in the article by van de Schraaf et al.
      • van de Schraaf S.A.J.
      • Rhodius-Meester H.F.M.
      • Aben L.
      • et al.
      Slowing: a vascular geriatric syndrome?.
      makes a strong case for associating 3 clinical expressions of slowness they have identified as a geriatric syndrome, gait speed, thought processing, and mood (apathy), with subcortical microvascular disease. There is support for their assertion in other research, as multiple studies have identified associations between physical manifestations of subcortical vascular disease, such as white matter hyperintensities, and motor slowness.
      • Ghanavati T.
      • Smitt M.S.
      • Lord S.R.
      • et al.
      Deep white matter hyperintensities, microstructural integrity and dual task walking in older people.
      • Hairu R.
      • Close J.C.T.
      • Lord S.R.
      • et al.
      The association between white matter hyperintensity volume and gait performance under single and dual task conditions in older people with dementia: a cross-sectional study.
      • Kilgour A.H.
      • Todd O.M.
      • Starr J.M.
      A systematic review of the evidence that brain structure is related to muscle structure and their relationship to brain and muscle function in humans over the lifecourse.
      There is also considerable literature linking cerebral small vessel disease with apathy.
      • Clancy U.
      • Gilmartin D.
      • Jochems A.C.C.
      • et al.
      Neuropsychiatric symptoms associated with cerebral small vessel disease: a systematic review and meta-analysis.
      And, of course, subcortical cognitive impairment is a well-known syndrome and, which when fully developed, is a subtype of vascular dementia.
      • Cannistraro R.J.
      • Badi M.
      • Eidelman B.H.
      • et al.
      CNS small vessel disease: a clinical review.
      • Chojdak-Łukasiewicz J.
      • Dziadkowiak E.
      • Zimny A.
      • Paradowski B.
      Cerebral small vessel disease: a review.
      • Wardlaw J.M.
      • Smith C.
      • Dichgans M.
      Small vessel disease: mechanisms and clinical implications.
      Indeed, these and possibly other symptoms have been previously described together as manifestations of subcortical vascular disease.
      • Chojdak-Łukasiewicz J.
      • Dziadkowiak E.
      • Zimny A.
      • Paradowski B.
      Cerebral small vessel disease: a review.
      One study alone does not, however, establish a scientific truth, and the article by van de Schraaf et al.
      • van de Schraaf S.A.J.
      • Rhodius-Meester H.F.M.
      • Aben L.
      • et al.
      Slowing: a vascular geriatric syndrome?.
      has a number of limitations.
      • To begin with, “slowing” implies a functional change over time, requiring longitudinal data; “slowness” is a more accurate label for what they are describing.
      • Furthermore, other domains need to be considered for the core features of a “slowness” syndrome to be identified and characterized beyond a set of manifestations of cerebrovascular disease.
      • In addition, if the authors' goal has been to identify markers of small vessel cerebrovascular disease, then further research and analyses are needed to confirm the strength of these relationships, such as sensitivity, specificity, and predictive value.
      • Finally, the study population itself is a limitation, as the data were drawn from a memory disorders clinic and, therefore, are not representative of the general geriatric population. Indeed, it is possible that what van de Schraaf et al.
        • van de Schraaf S.A.J.
        • Rhodius-Meester H.F.M.
        • Aben L.
        • et al.
        Slowing: a vascular geriatric syndrome?.
        are describing is a phenotype of cognitive decline rather than a more universal geriatric syndrome.

      Conclusion

      Slowness is worthy of consideration as a possible addition to the panoply of geriatric syndromes. It is common; it increases with age; and it has significant clinical and functional implications. However, much more research on different populations is needed to better characterize the manifestations and components of slowness, and to determine whether, and if so, how, slowness should be measured. Only additional research will tease out the areas of overlap and distinct differences between slowness and other syndromes, such as frailty and cognitive impairment, whose manifestations include abnormally slow function in specific physiological processes, thereby determining whether slowness or, if measured longitudinally, slowing is tied to cognitive and/or vascular disease or has a broader etiological and phenotypical profile.

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