Cognitive Compromise: Considerations in Individuals with Lower-limb Amputation

Twenty years ago, a rehabilitation team examined the cognitive function of 14 patients with lower-limb amputation secondary to peripheral vascular disease (PVD) and compared its observations against the cognitive performance of 14 able-bodied, matched controls. Participants with amputation had significantly slower psychomotor speed, poorer problem-solving ability, and more compromised abstract-reasoning skills than the healthy controls. There were additional trends toward poorer performance on measures of visuospatial skills, concentration, and oral fluency among the amputee cohort. 1 These were among the earliest observations to support the notion that the same factors that might lead to a lower-limb vascular amputation might also contribute to some level of cognitive compromise. A 2012 review article by Coffey et al. expands this conversation, pointing out that in addition to the physical competencies required during prosthetic rehabilitation, such as strength, balance, and coordination, there is a certain cognitive capacity needed to use and maintain an appropriately fitting prosthesis. 2 The authors assert that memory, attention, concentration, visuospatial function, and organizational abilities are requisite to successful prosthetic use. 2 Peripheral arterial disease (PAD) and diabetes both precipitate the majority of lower-limb amputations in industrialized societies. 2 Unfortunately, patients with lower-limb amputations may be particularly susceptible to cognitive impairments due to the collateral effects of these conditions. Furthermore, lower-limb amputation is becoming increasingly common among the elderly, for whom some level of cognitive decline might be reasonably expected. Prosthetists should be aware of the potential comorbid cognitive challenges that may accompany lower-limb amputation. This article will discuss the effects of PVD, diabetes, and aging upon cognitive function. Peripheral Vascular Disease According to data drawn from the National Limb Loss Information Center (NLLIC), PVD accounts for 82 percent of all amputations performed in the United States each year. 2 PVD is also considered to be a marker of generalized atherosclerosis. Consequently, its presence carries implications that pertain not only to the lower extremities, such as a vascular amputation, but also to overall cardiovascular health in general and cerebrovascular circulation in particular. 2-3 In a 2009 review article about PAD and cognitive function, Rafnsson et al. assert that once PVD has progressed to the levels of critical limb ischemia and gangrene, such as might precipitate amputation, severe atherosclerosis is likely to be present in other parts of the arterial system as well. 3 In addition to the decreased cognitive function identified in the cohort of subjects with lower-limb amputation secondary to PVD described in the 1993 study, 1 a complementary study examined the cognitive performance of 25 elderly subjects whose PVD had advanced to the point where they were scheduled for a femoropopliteal bypass surgery. 4 Much like the cohort of subjects with lower-limb amputation, these PVD patients performed significantly worse than a cohort of age-matched, vascularly healthy controls on a range of cognitive tests. Specifically, 25 percent of the bypass candidates had cognitive scores within the bottom 5 percent of the control subjects who had undergone elective total hip or knee replacement secondary to osteoarthritis. 4 In addition, the same cohort of bypass candidates had cognitive performance scores equal to those observed in patients who had experienced a transient ischemic attack, a more overt marker of cerebrovascular disease. 4 Further still, the same group of bypass candidates had comparable performance scores on frontal lobe function tests and memory tests as those observed among stroke patients. 4 In a separate, related study, the cognitive deficits observed among 16 PVD patients with a low Ankle-Brachial Index (ABI) and 13 PVD patients with lower-limb amputation were also similar to those observed among a cohort of stroke patients, with the stroke and PVD groups performing comparably on six of the eight cognitive tests administered. 5 Summarizing the literature, Rafnesson et al. clarified that patients with advanced PVD that might precipitate such events as bypass surgery or amputation may experience significant cognitive deficits that differ only in magnitude from those observed in patients who have suffered an overt stroke. 3 The relationship between PVD and cognitive decline becomes even more concerning when the cognitive function of patients with less severe forms of PVD are evaluated. Intermittent claudication (IC), described as pain or tightness in the calf or thigh with physical exertion and relieved by rest, is the most common clinical presentation of ischemia in the lower limbs. 3 As such, it represents a milder form of atherosclerotic disease than those populations described above. While the literature is mixed, there have been several studies that have observed lower cognitive performance scores in patients with IC compared to matched cohorts without it. 3 ABI, the ratio of blood pressure in the lower legs to blood pressure in the arms, is a common assessment of vascularity with which most prosthetists are familiar. As with amputation, bypass candidacy, and IC, lowered ABI has also been found to correlate with reduced cognitive performance in at least four studies. 3 These studies have suggested that there is an immediate relationship between ABI and cognitive ability, and that lowered ABI is largely predictive of compromised cognitive function later in life. 3 Taken collectively, the literature identifies a strong relationship between cognitive performance and PVD. These associations extend from the more extreme manifestations of PVD, such as amputation or bypass surgery, to its more benign presence in the forms of IC and lowered ABI. Diabetes According to Fosse et al., diabetes mellitus is present in almost half of all cases of lower-limb amputation. 6 As with PVD, it is strongly associated with various levels of cognitive compromise and decline. In their 2012 meta-analysis on the relationship between diabetes and cognitive impairment, Cheng et al. clarified that the cognitive changes associated with type 2 diabetes mainly affect learning, memory, mental flexibility, and mental speed, 7 all elements that would seem to affect a patient's ability to consistently use and manage a prosthesis. In contrast to the literature cited earlier with respect to PVD, where conclusions were generally drawn from smaller sample sizes, the relationship between diabetes and cognitive compromise is bolstered by a number of large, population-based studies. Using the meta-analysis technique, Cheng et al. combined the observations of several such studies to produce very strong statements about the relationship between diabetes and various types of cognitive decline. 7 For example, with respect to the relationship between diabetes and Alzheimer's disease, the authors combined the observations of 16 population-based studies, ultimately considering almost 42,000 individuals of whom 5,700 had diabetes. At the baselines of the individual studies, none of these subjects had cognitive impairment or Alzheimer's disease. However, subjects with diabetes were almost one and a half times more likely to develop Alzheimer's disease than those who did not have diabetes. 7 A similar analysis was performed on ten population-based studies to determine the extent to which diabetes was a risk factor for vascular dementia. In considering 26,500 individuals, 3,500 of whom had diabetes, those with diabetes were two and a half times more likely to develop vascular dementia than those without. 7 The authors were also able to combine the data from two population-based studies that considered the relationship between diabetes and the eventual presentation of mild cognitive impairment. In this analysis, there were 393 subjects with diabetes and 2,091 subjects without. Subjects with diabetes had a significantly higher incidence of any mild cognitive impairment than those without, with an increased relative risk of 1.21. 7 For their final analysis, the authors considered the relationship between diabetes and the development of any type of dementia. Combining the data from 11 population studies, inclusive of 5,247 people with diabetes and 32,900 people without, subjects with diabetes were one and a half times more likely to develop some form of dementia than those without. 7 Taken aggregately, these observations underscore the effects of diabetes as a risk factor for the development of cognitive impairments across their spectrum of severity. Age-associated Cognitive Decline In addition to the high prevalence of PVD and diabetes among individuals with lower-limb amputations, there has been a steady increase in the average age at which lower-limb amputations occur. Coffey et al. cite data from the United Kingdom's National Amputee Statistical Database suggesting that more than half of all individuals referred to prosthetic centers in the United Kingdom each year are over 65 years old, and that more than a quarter are over 75 years old. 2 This further contributes to the potential for some level of cognitive impairment among individuals with lower-limb amputation, as there appears to be a broad spectrum of cognitive decline associated with the aging process. At one extreme are the devastating effects of true clinical dementia. Less severe are several varieties of pathological "mild cognitive impairment." Still less severe is the phenomenon of normal, nonpathological, "age-associated cognitive decline." 8 While there is little age-associated decline in some mental functions like verbal ability, numerical processing, and general knowledge, other important mental capabilities such as memory, executive functions, processing speed, and reasoning begin to decline from middle age onward. 8 These cognitive elements have been described as "fluid" mental abilities and are important for carrying out everyday activities and independent living. 8 The causes of age-associated cognitive decline are multifactorial and may include several of the other considerations highlighted in this article that become more prevalent with the aging process such as vascular disease and diabetes. In addition, the brain experiences normal, age-associated structural changes. The most obvious of these is a steady decrease in brain size offset by increases in ventricular spaces and cerebral spinal fluid. This normal brain atrophy accelerates in old age and is likely affected by such things as hypertension, age-associated vascular changes, and oxidative stress. 8 However, it is readily apparent that some older adults are more resilient to the effects of these structural changes. This appears to be due, in part, to variations in "cognitive reserves," or the brain's capacity to buffer such effects. Determinants of cognitive reserve include cognitive ability in early life, educational level, and occupational complexity. In addition, empirical evidence supports the notion that the aging brain is able to compensate for the structural losses in functional areas by recruiting previously unrelated parts of the brain to take over some cognitive tasks. Taken together, these observations may help explain why the normal age-associated structural changes of the brain do not inevitably lead to cognitive decline. 8 Cognitive Impairments and Prosthetic Outcomes In their review of the topic, Coffey et al. identified six studies in which cognitive impairment among individuals with lower-limb amputations was associated with a failure to be successfully fitted with a prosthesis. 2 Among patients who were successfully fit, three studies found that poor cognitive functioning was related to less extensive use of their prostheses. 2 Five other studies found that poor cognitive function was associated with poorer mobility. 2 An example of these relationships is found in the work of Hanspal and Fisher, who quantified the cognitive and psychomotor function of 100 individuals with lower-limb amputations who were attending their outpatient prosthetic clinics. 9 The assessments were obtained using the standardized Clifton Assessment Procedures for the Elderly (CAPE). The instrument has several components including an information-orientation test; a mental abilities test that assesses counting, reading, and writing; and a psychomotor performance test in which subjects complete a timed spiral maze by tracing a circular route with a pencil. All three components-orientation, mental ability, and psychomotor function-were positively associated with mobility grade, with higher assessment scores correlated to greater mobility. 9 Further insights were gained by combining the three component scores to generate a total score for each subject. Among patients who had abandoned the use of a prosthesis, or who wore their prosthesis for transfers only and never walked without assistance, the composite score was observed at 17.6 and 23.2 respectively. By contrast, subjects capable of outdoor walking with intermittent use of walking aides and subjects with normal or near-normal gait generated composite scores of 32.9 and 34.3 respectively. Across the 100 study subjects, the authors found that 96 percent of the subjects whose composite score exceeded 30 were able to walk both indoors and outdoors. By contrast, only 2 percent of those subjects whose composite score was below 30 were able to walk outdoors. 9 Thus, cognitive and psychomotor function appear to be strongly associated with prosthetic mobility. Summary Daily use and maintenance of a lower-limb prosthesis is challenging. Evident physical demands include strength, balance, and coordination. However, there are additional cognitive requirements that affect an individual's ability to succeed with a prosthesis. Unfortunately, several of the attributes that increasingly characterize today's lower-limb amputee population appear to predispose them toward the development of some level of cognitive compromise. Clear relationships exist between cognitive decline and PVD, diabetes, and aging. Understanding that each of these presentations is a potential risk factor for varying levels of cognitive impairment will encourage clinicians to better appreciate and monitor the cognitive requirements of living with a lower-limb amputation and maintaining a lower-limb prosthesis. Phil Stevens, MEd, CPO, FAAOP, is in clinical practice with Hanger Clinic, Salt Lake City, Utah. He can be reached at philmstevens@hotmail.com References Phillips, N. A., C. C. Mate-Kole, and R. L. Kirby. 1993. Neuropsychological function in peripheral vascular disease amputee patients. Archives of Physical Medicine and Rehabilitation 74(12):1309-14. Coffey, L., F. O'Keeffe, P. Gallagher, D. Desmond, and R. Lombard-Vance. 2012. Cognitive functioning in persons with lower limb amputations: A review. Disability and Rehabilitation 34(23):1950-64. Rafnsson, S. B., I. J. Deary, and F. G. R. Fowkes. 2009. Peripheral arterial disease and cognitive function. Vascular Medicine 14:51-61. Rao, R., S. Jackson, and R. Howard. 1999. Neruropsychological impairment in stroke, carotid stenosis, and peripheral vascular disease. A comparison with healthy community residents. Stroke 30:2167-73. Phillips, N. A., and C. C. Mate-Kole. 1997. Cognitive deficits in peripheral vascular disease. A comparison of mild stroke patients and normal control subjects. Stroke 28:777-84. Fosse, S., A. Haremann-Heurtier, S.Jacqueminet, G. Ha Van, A. Grimaldi, and A. Fagot-Campagna. 2009. Incidence and characteristics of lower limb amputations in people with diabetes. Diabetic Medicine 226:391-6. Cheng, G., C. Huang, H. Deng, and H. Wang. 2012. Diabetes as a risk factor for dementia and mild cognitive impairment: A meta-analysis of longitudinal studies. Internal Medicine Journal 42(5):484-91. Deary, I. J., J. Corley, A. J. Gow, S. E. Harris, L. M. Houlihan, R. E. Marioni, L. Penks, S. B. Rafnsson, and J. M. Starr. 2009. Age-associated cognitive decline. British Medical Bulletin 92(1):135-152. Hanspal, R. S., and K. Fisher. 1991. Assessment of cognitive and psychomotor function and rehabilitation of elderly people with prostheses. British Medical Journal 302(6782):940.

Cognitive Compromise: Considerations in Individuals with Lower-limb Amputation

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