Review of Alzheimer's disease scales: is there a need for a new multi-domain scale for therapy evaluation in medical practice?

Philippe Robert, Steven Ferris, Serge Gauthier, Ralf Ihl, Bengt Winblad, Frank Tennigkeit, Philippe Robert, Steven Ferris, Serge Gauthier, Ralf Ihl, Bengt Winblad, Frank Tennigkeit

Abstract

Introduction: The present review of Alzheimer's disease (AD) rating scales aims to outline the need for a new rating scale to be used in routine clinical practice for long-term medical care of AD patients. An ideal scale would be: 1) practical, easy and quick to administer for an experienced clinician; 2) validated for AD; 3) multi-domain: covering the AD-relevant areas of cognition, activities of daily living, behavior, communication/social interaction, and quality of life; 4) applicable to all AD severity stages; 5) able to monitor disease progression; and 6) sensitive to measure therapy effects.

Methods: The National Library of Medicines' MEDLINE database was searched for the years 1981 to September 2008, using a set of keywords aiming to select instruments which cover at least some of the requirements for an ideal practical AD scale for therapy evaluation. Measures for AD staging and screening tests were not considered for review.

Results: Of 1,902 articles resulting from the literature search, 68 relevant AD scales were identified. Most of them were scales that predominantly measure the severity of major dysfunctions in particular AD domains. Only five scales met some of the requirements for a practical multi-domain AD scale, but did not possess all required characteristics.

Conclusions: Despite the multitude of AD scales for various purposes, there remains a need for a new multi-domain and easy to administer AD scale for assessment of disease progression and response to therapy in daily medical practice.

References

    1. Khachaturian ZS, Radebaugh TS, (Eds) Alzheimer's Disease: Cause(s), Diagnosis, Treatment, and Care. Boca Raton, FL: CRC Press; 1996.
    1. Geldmacher DS. Treatment guidelines for Alzheimer's disease: redefining perceptions in primary care. Prim Care Companion J Clin Psychiatry. 2007;9:113–121. doi: 10.4088/PCC.v09n0205.
    1. Schmitt FA, Wichems CH. A systematic review of assessment and treatment of moderate to severe Alzheimer's disease. Prim Care Companion J Clin Psychiatry. 2006;8:158–169. doi: 10.4088/PCC.v08n0306.
    1. Lawton MP. In: The Concept and Measurement of Quality of Life in the Frail Elderly. Barren JE, Lubben JE, Rowe JC, Deutschman DE, editor. New York: Academic Press; 1991. A multidimensional view of quality of life; pp. 3–27.
    1. Guideline on medicinal products for the treatment of Alzheimer's disease and other dementias (CPMP/EWP/553/95 Rev.1)
    1. Saxton J, Swihart AA. Neuropsychological assessment of the severely impaired elderly patient. Clin Geriatr Med. 1989;5:531–543.
    1. Livingston G, Katona C, François C, Guilaume C, Cochran J, Sapin C. Characteristics and health status change over 6 months in people with moderately severe to severe Alzheimer's disease in the U.K. Int Psychogeriatr. 2006;18:527–538. doi: 10.1017/S1041610205002942.
    1. Black R, Greenberg B, Ryan JM, Posner H, Seeburger J, Amatniek J, Resnick M, Mohs R, Miller DS, Saumier D, Carrillo MC, Stern Y. Scales as outcome measures for Alzheimer's disease. Alzheimers Dement. 2009;5:324–339. doi: 10.1016/j.jalz.2009.05.667.
    1. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–198. doi: 10.1016/0022-3956(75)90026-6.
    1. Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. 1992;40:922–935.
    1. Clark CM, Sheppard L, Fillenbaum GG, Galasko D, Morris JC, Koss E, Mohs R, Heyman A. Variability in annual Mini-Mental State score in patients with probable Alzheimer's disease: A clinical perspective of data from CERAD. Arch Neurol. 1999;56:857–962. doi: 10.1001/archneur.56.7.857.
    1. Hensel A, Angermeyer MC, Riedel-Heller SG. Measuring cognitive change in older adults: reliable change indices for the mini-mental state examination. J Neurol Neurosurg Psychiatry. 2007;78:1298–1303. doi: 10.1136/jnnp.2006.109074.
    1. Reisberg B. Global measures: utility in defining and measuring treatment response in dementia. Int Psychogeriatr. 2007;19:421–456. doi: 10.1017/S1041610207005261.
    1. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984;141:1356–1364.
    1. Doraiswamy MP, Kaiser L, Bieber F, Garman RL. The Alzheimer's disease assessment scale: Evaluation of psychometric properties and patterns of cognitive decline in multicenter clinical trials of mild to moderate Alzheimer's disease. Alzheimer Dis Assoc Disord. 2001;15:174–183. doi: 10.1097/00002093-200110000-00003.
    1. Mohs RC, Knopman D, Petersen RC, Ferris SH, Ernesto C, Grundman M, Sano M, Bieliauskas L, Geldmacher D, Clark C, Thal LJ. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment scale that broaden its scope. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S13–S21. doi: 10.1097/00002093-199700112-00003.
    1. Harrison J, Minassian SL, Jenkins L, Black RS, Koller M, Grundman M. A neuropsychological test battery for use in Alzheimer disease clinical trials. Arch Neurol. 2007;64:1323–1329. doi: 10.1001/archneur.64.9.1323.
    1. Saxton J, Swihart AA, McGonigle-Gibson KL, Miller VJ, Boller F. Assessment of the severely impaired patient: description and validation of a new neuropsychological test battery. Psychol Assess. 1990;2:298–303. doi: 10.1037/1040-3590.2.3.298.
    1. Saxton J, Kastango KB, Hugonot-Diener L, Boller F, Verny M, Sarles CE, Girgis RR, Devouche E, Mecocci P, Pollock BG, DeKosky ST. Development of a short form of the Severe Impairment Battery. Am J Geriatr Psychiatry. 2005;13:999–1005.
    1. Ferris S, Ihl R, Robert P, Winblad B, Gatz G, Tennigkeit F, Gauthier S. Severe Impairment Battery Language Scale, a language assessment tool for Alzheimer's disease patients. Alzheimer's Dement. 2009;5:375–379. doi: 10.1016/j.jalz.2009.04.1236.
    1. Peavy GM, Salmon DP, Rice VA, Galasko D, Samuel W, Taylor KI, Ernesto C, Butters N, Thal L. Neuropsychological assessment of severely demented elderly: the severe cognitive impairment profile. Arch Neurol. 1996;53:367–372.
    1. Erzigkeit H. In: Diagnosis and Treatment of Senile Dementia. Bergener M, Reisberg B, editor. Berlin: Springer-Verlag; 1989. The SKT: a short cognitive performance test as an instrument for the assessment of clinical efficacy of cognition enhancers; pp. 167–174.
    1. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. The Index of ADL: a standardized measure of biological and psychosocial function. JAMA. 1963;185:914–919.
    1. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9:179–186.
    1. Galasko D, Bennet D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11:s33–39. doi: 10.1097/00002093-199700112-00005.
    1. Gélinas I, Gauthier L, McIntyre M, Gauthier S. Development of a functional measure for persons with Alzheimer's disease: The disability assessment for dementia. Am J Occup Ther. 1999;53:471–481.
    1. Teunisse S, Derix MM. Measurement of activities of daily living in patients with dementia living at home: development of a questionnaire. Tijdschr Gerontol Geriatr. 1991;22:53–59.
    1. Hébert R, Guilbault J, Desrosiers J, Dubuc N. The functional autonomy measurement system (SMAF): A clinical-based instrument for measuring disabilities and handicaps in older people. Geriatrics Today: J Can Geriatr Soc. 2001;4:141–147.
    1. Linn MW. A rapid disability rating scale. J Am Geriatr Soc. 1967;15:211–214.
    1. Hindmarch I, Lehfeld H, Jongh P, Erzigkeit H. The Bayer Activities of Daily Living Scale (B-ADL) Dement Geriatr Cogn Disord. 1998;9:20–26. doi: 10.1159/000051195.
    1. Galasko D, Bennet D, Sano M, Marson D, Kaye J, Edland SD. Alzheimer's Disease cooperative Study. ADCS Prevention Instrument Project: assessment of instrumental activities of daily living for community-dwelling elderly individuals in dementia prevention clinical trials. Alzheimer Dis Assoc Disord. 2006;20:s152–169. doi: 10.1097/01.wad.0000213873.25053.2b.
    1. Pfeffer R, Kurosaki C, Harrah J, Chance S, Filos S. Measurement of functional activities of daily living of older adults in the community. J Gerontol. 1982;37:323–329.
    1. Sikkes SAM, de Lange-de Klerk ESM, Pijnenburg YAL, Scheltens P, Uitdehaag BMJ. A systematic review of instrumental activities of daily living scales in dementia: room for improvement. J Neurol Neurosurg Psychiatry. 2009;80:7. doi: 10.1136/jnnp.2008.155838.
    1. Guy W. ECDEU Assessment Manual for Psychopharmacology - Revised (DHEW Publ No ADM 76-338) Rockville, MD: Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH, Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976. Clinical Global Impression Scale; pp. 218–222.
    1. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982;140:566–572. doi: 10.1192/bjp.140.6.566.
    1. Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982;139:1136–1139.
    1. Reisberg B. Functional assessment staging (FAST) Psychopharmacol Bull. 1988;24:653–659.
    1. Schneider LS, Olin JT, Doody RS, Clark CM, Morris JC, Reisberg B, Schmitt FA, Grundman M, Thomas RG, Ferris SH. The Alzheimer's Disease Cooperative Study. Validity and reliability of the Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change. Alzheimer Dis Assoc Disord. 1997;11:22–32. doi: 10.1097/00002093-199700112-00004.
    1. Reisberg B, Ferris SH. In: Guide to Assessment Scales in Dementia. Kelly C, Newton-Howes G, editor. London: Science Press; 1994. Clinician's interview-based impression of change-plus.
    1. Reisberg B, Borenstein J, Salob SP, Ferris SH, Franssen E, Georgotas A. Behavioral symptoms in Alzheimer's disease: phenomenology and treatment. J Clin Psychiatry. 1987;48:9–15.
    1. Overall JE, Gorham DR. The brief psychiatric rating scale. Psycholog Rep. 1962;10:799–812. doi: 10.2466/PR0.10.3.799-812.
    1. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44:2308–2314.
    1. Kaufer DI, Cummings JL, Ketchel P, Smith V, MacMillan A, Shelley T, Lopez OL, DeKosky ST. Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. J Neuropsychiatry Clin Neurosci. 2000;12:233–239.
    1. Connor DJ, Sabbagh MN, Cummings JL. Comment on administration and scoring of the Neuropsychiatric Inventory in clinical trials. Alzheimers Dement. 2008;4:390–394. doi: 10.1016/j.jalz.2008.09.002.
    1. Tariot PN, Mack JL, Patterson MB, Edland SD, Weiner MF, Fillenbaum G, Blazina L, Teri L, Rubin E, Mortimer YA. et al.The Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer's Disease. The Behavioral Pathology Committee of the Consortium to Establish a Registry for Alzheimer's Disease. Am J Psychiatry. 1995;152:1349–1357.
    1. Baumgarten M, Becker R, Gauthier S. Validity and reliability of the dementia behavior disturbance scale. J Am Geriatr Soc. 1990;38:221–226.
    1. Cohen-Mansfield J. Agitated behaviors in elderly. Preliminary results in the cognitively deteriorated. J Am Geriatr Soc. 1986;34:722–727.
    1. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-1983;17:37–49. doi: 10.1016/0022-3956(82)90033-4.
    1. Robert PH, Clairet S, Benoit M, Koutaich J, Bertogliati C, Tible O, Caci H, Borg M, Brocker P, Bedoucha P. The apathy inventory: assessment of apathy and awareness in Alzheimer's disease, Parkinson's disease and mild cognitive impairment. Int J Geriatr Psychiatry. 2002;17:1099–1105. doi: 10.1002/gps.755.
    1. Sunderland T, Alterman IS, Yount D, Hill JL, Tariot PN, Newhouse PA, Mueller EA, Mellow AM, Cohen RM. A new scale for assessment of depressed mood in dementia patients. Am J Psychiatry. 1988;145:955–959.
    1. Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell scale for depression in dementia. Biol Psychiatry. 1988;23:271–284. doi: 10.1016/0006-3223(88)90038-8.
    1. Tappen RM, Williams C. Alzheimer's Mood Scale: Validity and reliability [abstract] Gerontolog Soc Am, 52nd Ann Sci Meeting, San Francisco. 1999.
    1. Ready RE, Ott BR. Quality of life measures for dementia. Health Qual Life Outcomes. 2003;1:11. doi: 10.1186/1477-7525-1-11.
    1. Lawton MP. Quality of life in Alzheimer disease. Alzheimer Dis Assoc Disord. 1994;8:138–150.
    1. Sands L, Ferriera P, Stewart A, Brod M, Yaffe K. What explains differences between dementa patients' and their caregivers' ratings of patients' quality of life? Am J Geriatr Psychiatry. 2004;12:272–280.
    1. Rockwood K, Graham JE, Fay S. ACADIE Investigators. Goal setting and attainment in Alzheimer's disease patients treated with donepezil. J Neurol Neurosurg Psychiatry. 2002;73:500–507. doi: 10.1136/jnnp.73.5.500.
    1. Rabins PV, Kasper JD, Kleinman L, Black BS, Patrick DL. Concepts and methods in the development of the ADRQL: An instrument for assessing health-related quality of life in persons with Alzheimer's disease. J Ment Health Aging. 1999;15:33–48.
    1. Brod M, Stewart AL, Sands L, Walton P. Conceptualization and measurement of quality of life in dementia: The dementia quality of life instrument (DQoL) Gerontologist. 1999;39:25–35.
    1. Logsdon RG, Gibbons LE, McCurry SM, Teri L. Quality of life in Alzheimer's Disease: patient and caregiver reports. Psychosom Med. 1999;64:510–519.
    1. Logsdon RG, Gibbons LE, McCurry SM, Teri L. Assessing the quality of life in older adults with cognitive impairment. Psychosom Med. 2002;64:510–519.
    1. Weiner MF, Martin-Cook K, Svetlik DA, Saine K, Foster B, Fontaine CS. The quality of life in late-stage dementia (QUALID) scale. J Am Med Dir Assoc. 2000;1:114–116.
    1. DeJong R, Osterlund OW, Roy GW. Measurement of quality of life changes in patients with Alzheimer's disease. Clinical Therapeutics. 1989;11:545–554.
    1. Moons P, Marquet K, Budts W, De Geest S. Validity, reliability and responsiveness of the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) in congenital heart disease. Health Qual Life Outcomes. 2004;2:27. doi: 10.1186/1477-7525-2-27.
    1. Hurley AC, Volicer BJ, Hanrahan PA, Houde S, Volicer L. Assessment of discomfort in advanced Alzheimer patients. Res Nurs Health. 1992;15:369–377. doi: 10.1002/nur.4770150506.
    1. Savundranayagam MY, Hummert ML, Montgomery RJV. Investigating the effects of communication problem on caregiver burden. J Gerontol B Psychol Sci Soc Sci. 2005;60B:s48–55.
    1. Powell JA, Hale MA, Bayer AJ. Symptoms of communication breakdown in dementia: Carers' perception. Eur J Disord Commun. 1995;30:65–75. doi: 10.3109/13682829509031323.
    1. Shader RI, Harmaz JS, Salzman C. A new scale for clinical assessment in geriatric populations: Sandoz Clinical Assessment - Geriatric (SCAG) J AM Geriatr Soc. 1974;22:107–103.
    1. Gottfries CG, Bråne G, Gullberg B, Steen G. A new rating scale for dementia syndromes. Arch Gerontol Geriatr. 1982;1:311–330. doi: 10.1016/0167-4943(82)90031-0.
    1. Bråne G, Gottfries CG, Winblad B. The Gottfries-Bråne-Steen scale: validity, reliability and application in anti-dementia drug trials. Dement Geriatr Cogn Disord. 2001;12:1–14. doi: 10.1159/000051230.
    1. Brunner C, Spiegel R. Eine Validierungsstudie mit der NOSGER, einem neuen Beurteilungsinstrument für die Psychogeriatrie. Zeitschrift für klinische Psychologie. 1990;19:211–229.
    1. van der Kam P, Mol F, Wimmers M. Beoordelingsschaal voor Oudere Patienten (BOP) Deventer, the Netherlands: Van Loghum Slaterus; 1971.
    1. Porzsolt F, Kojer M, Schmidl M, Greimel ER, Sigle J, Richter J, Eisemann M. A new instrument to describe indicators of well-being in old-old patients with severe dementia - The Vienna List. Health Qual Life Outcomes. 2004;2:10. doi: 10.1186/1477-7525-2-10.
    1. Venn RD. The Sandoz Clinical Assessment Geriatric (SCAG) scale. A general purpose psychiatric rating scale. Gerontology. 1983;29:185–198. doi: 10.1159/000213113.
    1. Richter J, Schwarz M, Eisemann M, Bauer B. Validation of the "Vienna List" as a proxy measure of quality of life. Qual Life Res. 2004;13:1725–1735. doi: 10.1007/s11136-004-8748-y.
    1. Gauthier S, Ihl R, Robert P, Winblad B, Ferris B, Tennigkeit F. Development of the Relevant Outcome Scale for Alzheimer's Disease (ROSA), a multi-domain assessment for daily medical practice. Abstracts from the 11th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy: Neurobiol Aging. 2010;31(Suppl 1)
    1. Ferris S, Ihl R, Robert P, Winblad B, Gauthier S, Holthoff V, Sternberg K, Tennigkeit F. Validation of the Relevant Outcome Scale for Alzheimer's disease (ROSA): a new instrument for daily medical practice. Abstracts from the 11th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy: Neurobiol Aging. 2010;31(Suppl 1)
    1. Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968;114:797–811. doi: 10.1192/bjp.114.512.797.
    1. Grevett C, O'Brien J. A new database for CAMCOG. Old Age Psychiatrist. 2002;28:9.
    1. Mattis S. In: Geriatric Psychiatry: A Handbook for Psychiatrics and Primary Care Physicians. Bellar L, Karasu T, editor. New York: Grune and Stratton; 1976. Mental status examination for organic mental syndrome in the elderly patient; pp. 77–101.
    1. Johnson N, Barion A, Rademaker A, Rehkemper G, Weintraub S. The Activities of Daily Living Questionnaire: A validation study in patients with dementia. Alzheimer Dis Assoc Disord. 2004;18:223–230.
    1. Bucks RS, Ashworth DL, Wilcock GK, Siegfried K. Assessment of activities of daily living in dementia: Development of the Bristol activities of daily living scale. Age and Ageing. 1996;25:113–120. doi: 10.1093/ageing/25.2.113.
    1. Bellelli G, Frisoni GB, Bianchetti A, Trabucchi M. The Bedford Alzheimer nursing deverity scale for the severely demented: validation study. Alzheimer Dis Assoc Disord. 1997;11:71–77. doi: 10.1097/00002093-199706000-00003.
    1. Mahoney FI, Barthel DW. Functional evaluation: The Barthel Index. Md State Med J. 1965;14:61–65.
    1. Schwartz GE. Development and validation of geriatric evaluation by relatives rating instrument (GERRI) Psychological Reports. 1983;53:479–488.
    1. Wilkinson IM, Graham-White J. Psychogeriatric dependency rating scale (PGDRS): a method of assessment for use by nurses. Br J Psychiatry. 1980;137:558–565. doi: 10.1192/bjp.137.6.558.
    1. Weintraub S. The record of independent living. An informant-completed measure of activities of daily living and behavior with cognitive impairment. Am J Alzheimer's Disease & Other Dementias. 1986;1:35–39.
    1. Knopman DS, Knapp MJ, Gracon SI, Davis CS. The Clinician Interview-Based Impression (CIBI): A clinician's global change rating scale in Alzheimer's disease. Neurology. 1994;44:2315–2321.
    1. Cole MG, Dastoor DP, Koszycki D. The hierarchic dementia scale. J Clin Exp Gerontol. 1983;5:219–234.
    1. Sihna D, Zemlan FP, Nelson S, Bienenfeld D, Thienhaus O, Ramaswamy G, Hamilton S. A new scale for assessing behavioral agitation in dementia. Psychiatry Res. 1992;41:73–88. doi: 10.1016/0165-1781(92)90020-4.
    1. Burns A, Beevor A, Lelliott P, Wing J, Blakey A, Orrell M, Mulinga J, Hadden S. Health of the nation outcome scales for elderly people (HoNOS 65+) Br J Psychiatry. 1999;174:424–427. doi: 10.1192/bjp.174.5.424.
    1. Sultzer DL, Berisford MA, Gunay I. The neurobehavioral rating scale: reliability in patients with dementia. J Psychiatr Res. 1995;29:185–191. doi: 10.1016/0022-3956(95)00018-Z.
    1. Teri L, Truax P, Logsdon R. Assessment of behavioral problems in dementia: The revised memory and behavior problems checklist. Psychol Aging. 1992;7:622–631. doi: 10.1037/0882-7974.7.4.622.
    1. Lawton MP, van Haitsma K, Perkinson M, Ruckdeschel K. Observed affect and quality of life in dementia: Further affirmations and problems. J Mental Health Aging. 1999;5:69–81.
    1. Bayles KA, Tomoeda CK, Trosset MW. Relation of linguistic communication abilities of Alzheimer's patients to stage of disease. Brain and Language. 1992;42:454–472. doi: 10.1016/0093-934X(92)90079-T.
    1. Shimokawa A, Yatomi N, Anamizu S, Ashikari I, Kohno M, Maki Y, Torii S, Isono H, Sugai Y, Koyama N, Matsuno Y. Comprehension of emotions: comparison between Alzheimer type and vascular type dementias. Dement Geriatr Cogn Dis. 2000;11:268–274. doi: 10.1159/000017249.
    1. Helmes E, Csapo KG, Short JA. Standardization and validation of the multidimensional observation scale for elderly subjects (MOSES) J Gerontol. 1987;42:395–405.
    1. Mozaz M, Rothi LJG, Anderson JM, Crucian GP, Heilman KM. Postural knowledge of transitive pantomimes and intransitive gestures. J Int Neuropsychol Soc. 2002;8:958–962. doi: 10.1017/S1355617702870114.
    1. Reilly MC. Development and testing of a new outcome measure of relationship between patients with Alzheimer's disease and their partners. Am J Alzheimers Dis Other Demen. 2006;21:249–257. doi: 10.1177/1533317506290665.
    1. Zigler E, Phillips L. Social competence and outcome in psychiatric disorder. J Abnorm Soc Psychology. 1961;63:264–271. doi: 10.1037/h0046232.

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