- Email: [email protected]
Dementia With Lewy Bodies: A Common Condition in Nursing Homes?
JAMDA 14 (2013) 713e714
JAMDA journal homepage: www.jamda.com
Editorial
Dementia With Lewy Bodies: A Common Condition in Nursing Homes? John E. Morley MB, BCh * Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, St. Louis, MO
Fritz Heinrich Lewy identified protein aggregates in parts of the brain other than the substantia nigra in persons with Parkinson disease in 1912. Today these are recognized as Lewy bodies, with their major component being a-synuclein associated with an ubiquitin protein.1 In the 1980s, dementia with Lewy bodies (DLB) was first diagnosed with the pathological association to a-synuclein.2 The diagnosis of DLB was not included in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), which was published in 1994. DSM-5 includes it as Major or Mild Neurocognitive Disorder with “Lewy Bodies.” DLB overlaps or coexists with Alzheimer disease (Lewy body variant of Alzheimer disease) and Parkinson disease dementia. Less than half of diffuse Lewy body dementia does not overlap pathologically with Alzheimer disease or Parkinson disease. The symptoms attributed to DLB are mainly due to loss of cholinergic neurons (cognitive dysfunction) and dopamine (hallucinations and motor symptoms). Although DLB has been clinically diagnosed in fewer than 5% of persons with dementia, Lewy bodies are found at postmortem in 20% to 40% of persons with dementing illnesses.3 The dichotomy between the lower prevalence of clear clinical symptoms of DLB and the much higher prevalence of Lewy bodies at autopsy has led to confusion in determining the exact prevalence of DLB. Although reasonable specificity can be obtained using diagnostic criteria, in general the diagnostic specificity is poor.4 The following are reasons to recognize DLB: The increased sensitivity to antidopaminergic drugs, making it important to avoid neuroleptics The awareness that DLB is commonly a cause of behavioral symptoms in residents in nursing homes The more rapid progression of DLB compared with Alzheimer disease5 The need to avoid antihistamines, antidepressants, anticholinergics, and benzodiazepines, and to take care with the choice of an anesthetic DLB tends to occur in persons older than 60 years. Although it is associated with cognitive impairment, memory loss is often less marked than in those with Alzheimer disease. Like people with delirium, there is a lack of attention and fluctuation throughout the day.6e9 Cognitive dysfunction is mainly in executive and visuospatial
* Address correspondence to John E. Morley, MB, BCh, Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, 1402 S. Grand Boulevard, M238, St. Louis, MO 63104. E-mail address: [email protected] (J.E. Morley).
areas.10e12 McKeith et al13 required 2 of the following 3 core features for the diagnosis of probable DLB: Fluctuating cognition with variation in attention Visual hallucinations Signs of Parkinson disease In many persons with DLB, a rapid eye movement sleep disorder is present a number of years before onset of the dementia. This includes nightmares associated with shouting out and abnormal movements of limbs.14 Behavioral disturbances and visual hallucinations are particularly common in DLB. For this reason, when a person demonstrates behavioral disturbances, the physician should consider DLB.15e19 Apathy is also particularly common early in DLB, particularly when the condition overlaps with Alzheimer disease.20,21 Persons with DLB are very likely to have falls, faints, and dizziness.22e25 Autonomic neuropathy with orthostasis and increased drooling is common. The autonomic neuropathy can be confirmed by finding uptake of iodine123 metaiodobenzylguanidine to be low in the heart, demonstrating decreased sympathetic activity.26 Table 1 provides the Saint Louis University Screening Test for DLB. The higher the score, the more likely that the person has DLB. At present, use of acetylcholine esterase inhibitors are considered an appropriate treatment for DLB. They appear to improve behavior, but whether or not they enhance cognition is uncertain.27 Care should be taken not to give anticholinergic agents, including medications for allergies, incontinence, and dizziness, and most antidepressants. Antipsychotics are an inappropriate therapy. Low doses of antiparkinsonism drugs may help if motor symptoms are present. Overall, DLB requires far more research to determine the ability of clinicians to make a meaningful diagnosis. As recommended by the International Association of Gerontology and Geriatrics nursing home Table 1 Saint Louis University Lewy Body Dementia Screen The higher the number of positive answers, the more likely the person has Lewy body dementia 1. Limited facial expression (masked faces) or axial rigidity 2. Shouting out at night 3. Movement of limbs while asleep 4. Daytime sleepiness 5. Visual hallucinations 6. Behavioral disinhibition 7. Apathy 8. Fluctuating alertness during the same day 9. Increased drooling (excess saliva) 10. Faints, falls, or dizziness
1525-8610/$ - see front matter Copyright Ó 2013 - American Medical Directors Association, Inc. http://dx.doi.org/10.1016/j.jamda.2013.07.009
714
Editorial / JAMDA 14 (2013) 713e714
consensus, controlled drug trials in nursing home residents are essential to guide future therapy.28 At present, limited use of medications would appear to be appropriate to avoid polypharmacy and precipitating side effects.29e33 DLB type, because of the increased falls and autonomic neuropathy, can play a major role in the pathogenesis of physical frailty.34e41 References 1. Goedert M, Spillantini MG, Del Tredici K, Braak H. 100 years of Lewy pathology. Nat Rev Neurol 2013;9:13e24. 2. Kosaka K, Yoshimura M, Ikeda K, Budka H. Diffuse type of Lewy body disease: Progressive dementia with abundant cortical Lewy bodies and senile changes of varying degreeda new disease? Clin Neuropathol 1984;3:185e192. 3. Hansen LA, Samuel W. Criteria for Alzheimer’s disease and the nosology of dementia with Lewy bodies. Neurology 1997;48:126e132. 4. Weisman D, McKeith I. Dementia with Lewy bodies. Semin Neurol 2007;27: 42e47. 5. Boyle PA, Wilson RS, Yu L, et al. Much of late life cognitive decline is not due to common neurodegenerative pathologies [published online ahead of print June 24, 2013]. Ann Neurol. http://dx.doi.org/10.1002/ana.23964. 6. Voyer P, Richard S, McCusker J, et al. Detection of delirium and its symptoms by nurses working in a long term care facility. J Am Med Dir Assoc 2012;13: 264e271. 7. Flaherty JH, Rudolph J, Shay K, et al. Delirium is a serious and under-recognized problem: Why assessment of mental status should be the sixth vital sign. J Am Med Dir Assoc 2007;8:273e275. 8. Bellelli G, Speciale S, Morghen S, et al. Are fluctuations in motor performance a diagnostic sign of delirium? J Am Med Dir Assoc 2011;12:578e583. 9. Saliba D, Jones M, Streim J, et al. Overview of significant changes in the Minimum Data Set for nursing homes version 3.0. J Am Med Dir Assoc 2012;13: 595e601. 10. Mollenhauer B, Förstl H, Deuschl G, et al. Lewy body and parkinsonian dementia: Common, but often misdiagnosed conditions. Dtsch Arztebl Int 2010;107:684e691. 11. Cholerton B, Larson EB, Baker LD, et al. Neuropathologic correlates of cognition in a population-based sample. J Alzheimers Dis 2013;36:699e709. 12. Cagnin A, Gnoato F, Jelcic N, et al. Clinical and cognitive correlates of visual hallucinations in dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2013;84:505e510. 13. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium. Neurology 2005;65: 1863e1872. 14. Pao WC, Boeve BF, Ferman TJ, et al. Polysomnographic findings in dementia with Lewy bodies. Neurologist 2013;19:1e6. 15. Rapp MA, Mell T, Majic T, et al. Agitation in nursing home residents with dementia (VIDEANT Trial): Effects of a cluster-randomized, controlled, guideline implementation trial. J Am Med Dir Assoc 2013;14:690e695. 16. Volicer L. Is your nursing home a battlefield? J Am Med Dir Assoc 2012;13: 195e196. 17. Morley JE. Dementia-related agitation. J Am Med Dir Assoc 2011;12:611e612.e2. 18. Volicer L. Behaviors in advanced dementia. J Am Med Dir Assoc 2009;10:146. author reply 146e147. 19. Volicer L. Toward better terminology of behavioral symptoms of dementia. J Am Med Dir Assoc 2012;13:3e4. 20. Volicer L, Frijters DH, van der Steen JT. Apathy and weight loss in nursing home residents: Longitudinal study. J Am Med Dir Assoc 2013;14:417e420.
21. Hölttä EH, Laakkonen ML, Laurila JV, et al. Apathy: Prevalence, associated factors, and prognostic value among frail, older inpatients. J Am Med Dir Assoc 2012;13:541e545. 22. Morley JE. Syncope. J Am Med Dir Assoc 2013;14:311e312. 23. Rapp K, Becker C, Cameron ID, et al. Epidemiology of falls in residential aged care: Analysis of more than 70,000 falls from residents of Bavarian nursing homes. J Am Med Dir Assoc 2012;13:187.e1e187.e6. 24. Messinger-Rapport BJ, Cruz-Oliver DM, Thomas DR, Morley JE. Clinical update on nursing home medicine: 2012. J Am Med Dir Assoc 2012;13:581e594. 25. Gama ZA, Medina-Mirapeix F, Saturno PJ. Ensuring evidence-based practices for falls prevention in a nursing home setting. J Am Med Dir Assoc 2011;12: 398e402. 26. Taki J, Yoshita M, Yamada M, Tonami N. Significance of 1231-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: It can be a specific marker for Lewy body disease. Ann Nucl Med 2004;18:453e461. 27. Touchon J, Bergman H, Bullock R, et al. Response to rivastigmine or donepezil in Alzheimer’s patients with symptoms suggestive of concomitant Lewy body pathology. Curr Med Res Opin 2006;22:49e59. 28. Tolson D, Rolland Y, Andrieu S, et al. The International Association of Gerontology and Geriatrics/World Health Organization/Society Française Gérontologie et de Gériatrie Task Force. International Association of Gerontology and Geriatrics: A global agenda for clinical research and quality of care in nursing homes. J Am Med Dir Assoc 2011;12:184e189. 29. Morley JE. Anticholinergic medications and cognition. J Am Med Dir Assoc 2011;12:543e543.e1. 30. Kojima G, Bell C, Tamura B, et al. Reducing cost by reducing polypharmacy: The polypharmacy outcomes project. J Am Med Dir Assoc 2012;13:818. e11e818.e15. 31. Morley JE. Polypharmacy in the nursing home. J Am Med Dir Assoc 2009;10: 289e291. 32. Tamura BK, Bell CL, Lubimir K, et al. Physician intervention for medication reduction in a nursing home: The polypharmacy outcomes project. J Am Med Dir Assoc 2011;12:326e330. 33. Fitzgerald SP, Bean NG. An analysis of the interactions between individual comorbidities and their treatmentsdimplications for guidelines and polypharmacy. J Am Med Dir Assoc 2010;11:475e484. 34. Morley JE, Vellas B, Abellan van Kan G, et al. Frailty consensus: A call to action. J Am Med Dir Assoc 2013;14:392e397. 35. Shimada H, Makizako H, Doi T, et al. Combined prevalence of frailty and mild cognitive impairment in a population of elderly Japanese people. J Am Med Dir Assoc 2013;14:518e524. 36. Rougé Bugat ME, Cestac P, Oustric S, et al. Detecting frailty in primary care: A major challenge for primary care physicians. J Am Med Dir Assoc 2012;13: 669e672. 37. Hoogendijk EO, van Hout HP. Investigating measurement properties of the Groningen Frailty Indicator: A more systematic approach is needed. J Am Med Dir Assoc 2012;13:757. 38. Peters LL, Boter H, Buskens E, Slaets JP. Measurement properties of the Groningen Frailty Indicator in home-dwelling and institutionalized elderly people. J Am Med Dir Assoc 2012;13:546e551. 39. Dent E, Visvanathan R, Piantadosi C, Chapman I. Use of the Mini Nutritional Assessment to detect frailty in hospitalized older people. J Nutr Health Aging 2012;16:764e767. 40. Subra J, Gillette-Guyonnet S, Cesari M, et al. The integration of frailty into clinical practice: Preliminary results from the Gérontopóle. J Nutr Health Aging 2012;16:714e720. 41. Morley JE, Malmstrom TK, Miller DK. A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans. J Nutr Health Aging 2012;16:601e608.
JAMDA journal homepage: www.jamda.com
Editorial
Dementia With Lewy Bodies: A Common Condition in Nursing Homes? John E. Morley MB, BCh * Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, St. Louis, MO
Fritz Heinrich Lewy identified protein aggregates in parts of the brain other than the substantia nigra in persons with Parkinson disease in 1912. Today these are recognized as Lewy bodies, with their major component being a-synuclein associated with an ubiquitin protein.1 In the 1980s, dementia with Lewy bodies (DLB) was first diagnosed with the pathological association to a-synuclein.2 The diagnosis of DLB was not included in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), which was published in 1994. DSM-5 includes it as Major or Mild Neurocognitive Disorder with “Lewy Bodies.” DLB overlaps or coexists with Alzheimer disease (Lewy body variant of Alzheimer disease) and Parkinson disease dementia. Less than half of diffuse Lewy body dementia does not overlap pathologically with Alzheimer disease or Parkinson disease. The symptoms attributed to DLB are mainly due to loss of cholinergic neurons (cognitive dysfunction) and dopamine (hallucinations and motor symptoms). Although DLB has been clinically diagnosed in fewer than 5% of persons with dementia, Lewy bodies are found at postmortem in 20% to 40% of persons with dementing illnesses.3 The dichotomy between the lower prevalence of clear clinical symptoms of DLB and the much higher prevalence of Lewy bodies at autopsy has led to confusion in determining the exact prevalence of DLB. Although reasonable specificity can be obtained using diagnostic criteria, in general the diagnostic specificity is poor.4 The following are reasons to recognize DLB: The increased sensitivity to antidopaminergic drugs, making it important to avoid neuroleptics The awareness that DLB is commonly a cause of behavioral symptoms in residents in nursing homes The more rapid progression of DLB compared with Alzheimer disease5 The need to avoid antihistamines, antidepressants, anticholinergics, and benzodiazepines, and to take care with the choice of an anesthetic DLB tends to occur in persons older than 60 years. Although it is associated with cognitive impairment, memory loss is often less marked than in those with Alzheimer disease. Like people with delirium, there is a lack of attention and fluctuation throughout the day.6e9 Cognitive dysfunction is mainly in executive and visuospatial
* Address correspondence to John E. Morley, MB, BCh, Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, 1402 S. Grand Boulevard, M238, St. Louis, MO 63104. E-mail address: [email protected] (J.E. Morley).
areas.10e12 McKeith et al13 required 2 of the following 3 core features for the diagnosis of probable DLB: Fluctuating cognition with variation in attention Visual hallucinations Signs of Parkinson disease In many persons with DLB, a rapid eye movement sleep disorder is present a number of years before onset of the dementia. This includes nightmares associated with shouting out and abnormal movements of limbs.14 Behavioral disturbances and visual hallucinations are particularly common in DLB. For this reason, when a person demonstrates behavioral disturbances, the physician should consider DLB.15e19 Apathy is also particularly common early in DLB, particularly when the condition overlaps with Alzheimer disease.20,21 Persons with DLB are very likely to have falls, faints, and dizziness.22e25 Autonomic neuropathy with orthostasis and increased drooling is common. The autonomic neuropathy can be confirmed by finding uptake of iodine123 metaiodobenzylguanidine to be low in the heart, demonstrating decreased sympathetic activity.26 Table 1 provides the Saint Louis University Screening Test for DLB. The higher the score, the more likely that the person has DLB. At present, use of acetylcholine esterase inhibitors are considered an appropriate treatment for DLB. They appear to improve behavior, but whether or not they enhance cognition is uncertain.27 Care should be taken not to give anticholinergic agents, including medications for allergies, incontinence, and dizziness, and most antidepressants. Antipsychotics are an inappropriate therapy. Low doses of antiparkinsonism drugs may help if motor symptoms are present. Overall, DLB requires far more research to determine the ability of clinicians to make a meaningful diagnosis. As recommended by the International Association of Gerontology and Geriatrics nursing home Table 1 Saint Louis University Lewy Body Dementia Screen The higher the number of positive answers, the more likely the person has Lewy body dementia 1. Limited facial expression (masked faces) or axial rigidity 2. Shouting out at night 3. Movement of limbs while asleep 4. Daytime sleepiness 5. Visual hallucinations 6. Behavioral disinhibition 7. Apathy 8. Fluctuating alertness during the same day 9. Increased drooling (excess saliva) 10. Faints, falls, or dizziness
1525-8610/$ - see front matter Copyright Ó 2013 - American Medical Directors Association, Inc. http://dx.doi.org/10.1016/j.jamda.2013.07.009
714
Editorial / JAMDA 14 (2013) 713e714
consensus, controlled drug trials in nursing home residents are essential to guide future therapy.28 At present, limited use of medications would appear to be appropriate to avoid polypharmacy and precipitating side effects.29e33 DLB type, because of the increased falls and autonomic neuropathy, can play a major role in the pathogenesis of physical frailty.34e41 References 1. Goedert M, Spillantini MG, Del Tredici K, Braak H. 100 years of Lewy pathology. Nat Rev Neurol 2013;9:13e24. 2. Kosaka K, Yoshimura M, Ikeda K, Budka H. Diffuse type of Lewy body disease: Progressive dementia with abundant cortical Lewy bodies and senile changes of varying degreeda new disease? Clin Neuropathol 1984;3:185e192. 3. Hansen LA, Samuel W. Criteria for Alzheimer’s disease and the nosology of dementia with Lewy bodies. Neurology 1997;48:126e132. 4. Weisman D, McKeith I. Dementia with Lewy bodies. Semin Neurol 2007;27: 42e47. 5. Boyle PA, Wilson RS, Yu L, et al. Much of late life cognitive decline is not due to common neurodegenerative pathologies [published online ahead of print June 24, 2013]. Ann Neurol. http://dx.doi.org/10.1002/ana.23964. 6. Voyer P, Richard S, McCusker J, et al. Detection of delirium and its symptoms by nurses working in a long term care facility. J Am Med Dir Assoc 2012;13: 264e271. 7. Flaherty JH, Rudolph J, Shay K, et al. Delirium is a serious and under-recognized problem: Why assessment of mental status should be the sixth vital sign. J Am Med Dir Assoc 2007;8:273e275. 8. Bellelli G, Speciale S, Morghen S, et al. Are fluctuations in motor performance a diagnostic sign of delirium? J Am Med Dir Assoc 2011;12:578e583. 9. Saliba D, Jones M, Streim J, et al. Overview of significant changes in the Minimum Data Set for nursing homes version 3.0. J Am Med Dir Assoc 2012;13: 595e601. 10. Mollenhauer B, Förstl H, Deuschl G, et al. Lewy body and parkinsonian dementia: Common, but often misdiagnosed conditions. Dtsch Arztebl Int 2010;107:684e691. 11. Cholerton B, Larson EB, Baker LD, et al. Neuropathologic correlates of cognition in a population-based sample. J Alzheimers Dis 2013;36:699e709. 12. Cagnin A, Gnoato F, Jelcic N, et al. Clinical and cognitive correlates of visual hallucinations in dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2013;84:505e510. 13. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium. Neurology 2005;65: 1863e1872. 14. Pao WC, Boeve BF, Ferman TJ, et al. Polysomnographic findings in dementia with Lewy bodies. Neurologist 2013;19:1e6. 15. Rapp MA, Mell T, Majic T, et al. Agitation in nursing home residents with dementia (VIDEANT Trial): Effects of a cluster-randomized, controlled, guideline implementation trial. J Am Med Dir Assoc 2013;14:690e695. 16. Volicer L. Is your nursing home a battlefield? J Am Med Dir Assoc 2012;13: 195e196. 17. Morley JE. Dementia-related agitation. J Am Med Dir Assoc 2011;12:611e612.e2. 18. Volicer L. Behaviors in advanced dementia. J Am Med Dir Assoc 2009;10:146. author reply 146e147. 19. Volicer L. Toward better terminology of behavioral symptoms of dementia. J Am Med Dir Assoc 2012;13:3e4. 20. Volicer L, Frijters DH, van der Steen JT. Apathy and weight loss in nursing home residents: Longitudinal study. J Am Med Dir Assoc 2013;14:417e420.
21. Hölttä EH, Laakkonen ML, Laurila JV, et al. Apathy: Prevalence, associated factors, and prognostic value among frail, older inpatients. J Am Med Dir Assoc 2012;13:541e545. 22. Morley JE. Syncope. J Am Med Dir Assoc 2013;14:311e312. 23. Rapp K, Becker C, Cameron ID, et al. Epidemiology of falls in residential aged care: Analysis of more than 70,000 falls from residents of Bavarian nursing homes. J Am Med Dir Assoc 2012;13:187.e1e187.e6. 24. Messinger-Rapport BJ, Cruz-Oliver DM, Thomas DR, Morley JE. Clinical update on nursing home medicine: 2012. J Am Med Dir Assoc 2012;13:581e594. 25. Gama ZA, Medina-Mirapeix F, Saturno PJ. Ensuring evidence-based practices for falls prevention in a nursing home setting. J Am Med Dir Assoc 2011;12: 398e402. 26. Taki J, Yoshita M, Yamada M, Tonami N. Significance of 1231-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: It can be a specific marker for Lewy body disease. Ann Nucl Med 2004;18:453e461. 27. Touchon J, Bergman H, Bullock R, et al. Response to rivastigmine or donepezil in Alzheimer’s patients with symptoms suggestive of concomitant Lewy body pathology. Curr Med Res Opin 2006;22:49e59. 28. Tolson D, Rolland Y, Andrieu S, et al. The International Association of Gerontology and Geriatrics/World Health Organization/Society Française Gérontologie et de Gériatrie Task Force. International Association of Gerontology and Geriatrics: A global agenda for clinical research and quality of care in nursing homes. J Am Med Dir Assoc 2011;12:184e189. 29. Morley JE. Anticholinergic medications and cognition. J Am Med Dir Assoc 2011;12:543e543.e1. 30. Kojima G, Bell C, Tamura B, et al. Reducing cost by reducing polypharmacy: The polypharmacy outcomes project. J Am Med Dir Assoc 2012;13:818. e11e818.e15. 31. Morley JE. Polypharmacy in the nursing home. J Am Med Dir Assoc 2009;10: 289e291. 32. Tamura BK, Bell CL, Lubimir K, et al. Physician intervention for medication reduction in a nursing home: The polypharmacy outcomes project. J Am Med Dir Assoc 2011;12:326e330. 33. Fitzgerald SP, Bean NG. An analysis of the interactions between individual comorbidities and their treatmentsdimplications for guidelines and polypharmacy. J Am Med Dir Assoc 2010;11:475e484. 34. Morley JE, Vellas B, Abellan van Kan G, et al. Frailty consensus: A call to action. J Am Med Dir Assoc 2013;14:392e397. 35. Shimada H, Makizako H, Doi T, et al. Combined prevalence of frailty and mild cognitive impairment in a population of elderly Japanese people. J Am Med Dir Assoc 2013;14:518e524. 36. Rougé Bugat ME, Cestac P, Oustric S, et al. Detecting frailty in primary care: A major challenge for primary care physicians. J Am Med Dir Assoc 2012;13: 669e672. 37. Hoogendijk EO, van Hout HP. Investigating measurement properties of the Groningen Frailty Indicator: A more systematic approach is needed. J Am Med Dir Assoc 2012;13:757. 38. Peters LL, Boter H, Buskens E, Slaets JP. Measurement properties of the Groningen Frailty Indicator in home-dwelling and institutionalized elderly people. J Am Med Dir Assoc 2012;13:546e551. 39. Dent E, Visvanathan R, Piantadosi C, Chapman I. Use of the Mini Nutritional Assessment to detect frailty in hospitalized older people. J Nutr Health Aging 2012;16:764e767. 40. Subra J, Gillette-Guyonnet S, Cesari M, et al. The integration of frailty into clinical practice: Preliminary results from the Gérontopóle. J Nutr Health Aging 2012;16:714e720. 41. Morley JE, Malmstrom TK, Miller DK. A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans. J Nutr Health Aging 2012;16:601e608.