Journal ofGenmtologx: MEDICAL SCIENCES 1992. Vol. 47, No. 6. MI77-MI82
Copyright 1992 by The Geronlological Society of America
Functional Status and Clinical Findings in Patients With Alzheimer's Disease Sally Freds, 1 Donna Cohen,3 Carl Eisdorfer,4 Gregory Paveza,1 Philip Gorelick,5 Daniel J. Luchins,6 Robert Hirschman,7 J. Wesson Ashford,8 Paul Levy,1 Todd Semla,2 and Helen Shaw1
We analyzed the association of clinical findings with impaired functional status, i.e., activities of daily living (ADLs), in a sample of 240 patients diagnosed with Alzheimer's disease by NINCDSIADRDA or DSM-I1I-R criteria. Logistic regression models were used to determine independent predictors of both the number of ADL impairments and number of ADL impairments characterized as moderate to severe. Two psychiatric problems, behavioral disorders and apathy, as well as a history of hypertension were significantly associated with ADL impairment independent of age, sex, race, and cognitive impairment. Behavioral disorders and apathy were also significantly associated with moderate to severe ADL impairment, but hypertension was not significant at this level.
A LZHEIMER'S disease (AD) is characterized by a pro* * • gressive loss of cognitive and functional capacities as well as neuropsychiatric problems (1-5). At present, the course of the disease cannot be reversed, and until effective treatments are available, clinical management strategies will continue to focus on maximizing health and functional effectiveness as well as emotional well-being (6,7). Because medical problems can have a major impact on the way older persons carry out basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs) (8,9), it is reasonable to assume that health problems are also related to the daily life activities of individuals with AD. Cognitive impairment is related to diminished functional status in AD (10-13), but it is not known to what extent the coexistence of cognitive impairment with other physical, psychiatric, or neurologic problems is associated with functional impairment. At least one study (14) has demonstrated the independent effects of the presence of clinical depression on the performance of I ADLs, but not ADLs, in AD patients. A few studies have also shown that interventions targeting comorbid or coexisting conditions have reduced patient discomfort and improved functioning (15,16). To our knowledge, no study has investigated the association of concurrent psychiatric and neurologic signs and symptoms as well as physical conditions with functional impairment in AD patients. This article reports the prevalence of the most common coexisting clinical symptoms and conditions and analyzes their independent associations with functional status. We hypothesized that the most prevalent coexisting clinical conditions and symptoms would be related to decreased functional status as measured by ADL
impairments beyond the effect of the cognitive loss directly attributable to AD. METHODS
Data set. — The 240 subjects in this study were selected from an Alzheimer's Disease Patient Registry known as the Prototype Alzheimer's Collaborative Team (PACT). PACT was established to study the feasibility and costs of establishing and operating a large-scale multisite registry for research on AD and other dementias. Methods and procedures for case ascertainment and enrollment as well as data management have been described (17), and several methodological papers are being written. Briefly, PACT consists of a Data Coordinating and Analysis Center at the University of Illinois at Chicago which registered patients evaluated and diagnosed at six medical sites: the Memory Disorders Clinic at the Mount Sinai Medical Center, Miami Beach; the Memory Disorders Clinic at the University of Miami Jackson Memorial Hospital; the Geriatrics Institute, University of Wisconsin-Milwaukee Clinical Campus; the Regional Alzheimer's Disease Center, Southern Illinois University School of Medicine; the Alzheimer's Disease Center, Michael Reese Hospital and Medical Center; and the University of Chicago School of Medicine Geriatric Clinic. Four of the six sites evaluated dementia patients using their own standardized protocols for psychiatric, neurological, physical, psychological, and psychosocial examinations of patients by an interdisciplinary medical team. The remaining two sites used dementia protocols, but patients were not evaluated by an interdisciplinary team. M177
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
'School of Public Health and 2College of Pharmacy, University of Illinois at Chicago, department of Aging and Mental Health, University of Southern Florida, Tampa. "Department of Psychiatry, University of Miami. 5 Department of Neurology, Rush-Presbyterian-St. Luke's Medical Center, Chicago. "Department of Psychiatry, University of Chicago. 'Department of Psychiatry, University of Wisconsin-Milwaukee. 'Department of Psychiatry, VA Medical Center, Martinez, California.
M178
FREELSETAL.
Variables. —The variables used in this analysis were four sets of measures from the PACT case enrollment form: sociodemographic information, i.e., age, race, and sex; results of the psychiatric, neurologic, and physical examinations by respective specialists at the PACT centers; ratings of functional status by the psychiatrist on six ADLs; and MiniMental State Examination (MMSE) test scores. The results of psychiatric, neurologic, and physical examinations were coded to note the presence or absence of specific conditions, signs, and symptoms observed during the multidisciplinary evaluation of the patient's dementia. Missing or unclear items were coded as unknown, but only patients with complete data, i.e., no unknown values, were used in this analysis. The possible range of signs and symptoms recorded after psychiatric interviews included agitation, depressed mood and other depressive symptoms, apathy (i.e., absence of emotion or emotional withdrawal), insomnia, behavioral disorders (e.g., screaming, wandering, catastrophic reactions, aggressivity), hallucinations, paranoia, delusions, and emotional lability. Psychiatrists examining patients at each site recorded symptoms as present or absent on a dementia interview protocol and also administered a Hamilton Depression Rating Scale (19). The possible range of symptoms recorded from neurologic examinations included agnosia, aphasia, apraxia, dizziness, dysarthria, dysphoria, gait problems, headache, paresthesia, seizures, weakness (upper and lower motor neuron), extrapyramidal signs (not due to drugs), abnormal muscle stretch reflex, presence of glabellar, suck, snout, or Babinski reflexes, and alterations in sensation. Neurologists examining patients at each site recorded signs and symptoms on a dementia examination protocol. Acute and chronic conditions documented after a physical examination and medical history included myocardial in-
farction or chronic cardiovascular disease; hypertension or history of hypertension; chronic renal, hepatic, pulmonary, or endocrine disease; history of stroke; hypoglycemia; diabetes; thyroid disorders; severe visual and hearing impairment; alcoholism or substance abuse; and tremors not due to drugs. Functional status included ratings of impairment on six ADLs — dressing, bathing, eating, walking, transferring, and toileting — at the time of evaluation or diagnosis. Patients were rated using a 4-point scale: 1 = able to do easily, 2 = has some difficulty, 3 = has great difficulty, and 4 = unable to do ADL. For the analyses, ratings were dichotomized two ways: to reflect whether or not there was any ADL impairment (grouping categories 2-4 vs 1), and to reflect whether or not there was moderate to severe impairment on ADLs (grouping categories 1-2 vs 3-4). For each coding scheme, ADL impairment ratings were added together to produce two summary scores reflecting functional status: number of ADL impairments and number of ADL impairments characterized as moderate to severe. Data analysis. —Multiple logistic regression was used to test the associations of clinical symptoms and conditions with ADL impairment independent of age, sex, race, cognitive impairment, and other significant conditions and symptoms. Only those symptoms and conditions appearing in 10% or more of the sample were selected for analysis. Logistic regression for ordered categorical outcomes (20) was used to analyze the number of ADL impairments, ranging from zero to six, as a dependent variable; symptoms, conditions, and other covariates were used as independent variables. Two models are available for ordered outcomes: proportional odds and nonproportional odds (21). Under the proportional odds model, odds ratios for the effect of each independent variable are assumed to be equal across different cutoff points. For example, if severe visual impairment were found to be significantly associated with the number of ADL impairments, the proportional odds model posits that the relative odds of having one or more ADL impairments (for patients with severe visual impairment compared to patients without) is equal to the relative odds of having two or more, three or more, and so on. The nonproportional odds model, on the other hand, includes additional parameters allowing estimates of different odds ratios for different cutoff points in the outcome. The advantage of the nonproportional odds model is that estimates of different odds ratios for different cutoff points provide a good description of changing magnitudes of associations with increasing functional impairment. The disadvantage is that the extra degrees of freedom used to estimate additional parameters result in less powerful tests of the overall effect of each condition or symptom. For this reason, the nonproportional odds model was used for variable selection. A forward stepwise selection procedure was used to select the best combination of symptoms and conditions associated with functional status, controlling for age, sex, race, and MMSE score, with a proportional odds multiple logistic regression equation. A nonproportional odds model was also fit for the variables in the final selected model in order to estimate different odds ratios under different cutoff points
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
PACT contains diagnostic, psychosocial, and sociodemographic data on a total of 1,402 persons with Alzheimer's disease, multi-infarct dementia, or related disorders from the six sites. A sociodemographic profile of the registry population has been published elsewhere (17), and comparisons of cases across centers are being analyzed. In order to be enrolled in PACT, patients had to be 40 years or older, living in the community at the time of diagnosis, and diagnosed between 1987 and 1989. The 240 cases selected for this analysis met three criteria. Subjects first had to have a diagnosis of probable or possible Alzheimer's disease by NINCDS-ADRDA criteria (5), Alzheimer's disease by DSM-III-R criteria (2), or primary degenerative dementia of the Alzheimer type by DMS-III-R criteria (2) (n = 671). Second, registry files had to have complete information documenting the results of physical, neurologic, and psychiatric examinations, including ratings of functional status by a multidisciplinary team (n = 348). Finally, a Mini-Mental State Examination (MMSE) score using the full 30-point Folstein instrument (18) had to be recorded (n = 240). The 240 cases analyzed here come from the four sites where the multidisciplinary evaluation included independent examinations by an internist, neurologist, psychiatrist, and psychologist as well as a social worker.
FUNCTIONAL STATUS IN AD
M179
Table 1. Prevalence of ADL Impairments (N = 240) Any Impairment Number of ADL Impairments
Number of Patients 100 43 36 17 24 9 11
Moderate to Severe Impairment Percent of Patients
Number of ADL Impairments
41.7%
163 43 10 11 6 3 4
17.9 15.0 7.1 10.0 3.8 4.6
Any Impairment Individual ADLs
89 80 80 53 37 34
Percent of Patients 67.9% 17.9 4.2 4.6 2.5 1.2 1.7
Moderate to Severe Impairment Percent of Patients 37.1% 33.3 33.3 22.1 15.4 14.2
for the number of ADL impairments. Finally, the set of independent variables selected were fit to binary logistic regression models predicting each ADL separately. RESULTS
The average age of the AD patients was 74.5 (SD = 7.8) years with a M/F sex ratio of 0.6. The average MMSE score was 15.5 (SD = 7.4). A score of 21 marked the 75th percentile and a score of 9 marked the 25th percentile of the distribution of patient scores. The average duration of dementia from the earliest onset of dementia symptoms to evaluation or diagnosis at the enrolling clinical center was 3.4 years (SD = 2.6). The case enrollment form contained the month and year of diagnosis or evaluation at the center, the month and year of reported earliest onset of dementia, as well as a checklist of possible symptoms reported to mark the onset of dementia, e.g., language difficulties, confusion, difficulties at work, and social occasions or with family. Prevalence offunctional impairment. — The distribution of the number of ADL impairments and the prevalence of each ADL impairment are reported in Table 1. A total of 58.3% of the sample was impaired on one or more ADLs, with over half of this subset (32.9%) impaired on one or two ADLs and the rest impaired on three or more ADLs. Of the sample, 32.1 % had moderate to severe impairment on one or more ADLs. The most prevalent ADL impairments were dressing (37.1% had any impairment; 12.9% had moderate to severe impairment), bathing (33.3% had any impairment; 11.7% had moderate to severe impairment), and transferring (33.3% had any impairment; 22.9% had moderate to severe impairment). Prevalence of clinical symptoms and conditions. — Table 2 reports the observed prevalence of psychiatric and neurologic signs and symptoms as well as acute and chronic physical conditions occurring in 10% or more of the sample
Individual ADLs Dressing Bathing Transferring Toileting Walking Eating
Number of Patients 31 28 55 21 9 15
Percent of Patients 12.9% 11.7 22.9 8.8 3.8 6.3
Table 2. Prevalence of Clinical Symptoms and Conditions (N = 240) Number of Patients
Percent of Patients
Psychiatric Symptoms: Agitation Depressive symptoms Behavioral disorders Apathy Insomnia Delusions Paranoia Hallucinations
72 65 52 48 37 27 26 25
30.0% 27.1 21.7 20.0 15.4 11.3 10.8 10.4
Neurologic Symptoms: Apraxia Dysphoria Aphasia Alteration in sensations
56 50 32 24
23.3 20.8 13.3 10.0
Physical Conditions: History of hypertension MI or cardiovascular disease Severe visual impairment Thyroid disorder
76 47 29 24
31.7 19.6 12.1 10.0
at the time of diagnosis or evaluation at the PACT center. The four most common psychiatric problems were agitation (30.0%), depressive mood and symptoms (27.1%), behavioral disorders (21.7%), and apathy (20.0%). Agitation cooccurred with depression in 14.2% of patients, with behavioral disorders in 11.2% of patients and with apathy in 12.1% of patients. The most prevalent reported neurologic symptom was apraxia (23.3%). The most common physical conditions were a history of hypertension (31.7%) and a history of myocardial infarction/chronic cardiovascular disease (19.6%), which also occurred together in 7.1% of the sample.
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
Dressing Bathing Transferring Toileting Walking Eating
Number of Patients
Number of Patients
FREELSETAL.
M180
Table 3. Best Selected Multiple Logistic Regression Model Predicting Functional Status (Number of ADL Impairments) Controlling for Age, Sex, Race, and Mental Status (MMSE) (N = 240) Independent Variables
Behavioral Disorders
Apathy
History of Hypertension
Adjusted odds ratios*
2.16
1.84
1.97
(1.18,3.93)
(1.00,3.37)
(1.16,3.34)
(95% confidence intervals) Adjusted odds ratiost for any difficulty with: s= 1 ADLs vs = 0 ADLs 55 2 ADLs vs < 2 ADLs ss 3 ADLs vs < 3 ADLs & 4 ADLs vs < 4 ADLs 5* 5 ADLs vs < 5 ADLs 6 ADLs vs < 6 ADLs
4.52 1.52 2.54 1.59 1.71 1.83
2.76 1.57 1.39 1.32 2.18 3.19
*Results of fitting a proportional odds model. tResults of fitting a nonproportional odds model.
1.72 2.04 1.81 2.21 2.92 5.46
The results of fitting multiple logistic regression models with individual ADL impairments as the dependent variable are shown in Table 5. Defining ADL impairment as having any difficulty, behavioral disorders were associated with impairments in transferring; apathy was associated with impairments in transferring and walking; and a history of hyperTable 4. Best Selected Multiple Logistic Regression Model Predicting Functional Status (Number of Moderate to Severe ADL Impairments) Controlling for Age, Sex, Race, and Mental Status (MMSE) (N = 240) Behavioral Disorders
Independent Variables Adjusted odds ratios* (95% confidence intervals) Adjusted odds ratiost for moderate to severe difficulty with: S3 1 ADLs vs = 0 ADLs S3 2 ADLs vs < 2 ADLs S3 3 ADLs vs < 3 ADLs ss 4 ADLs vs < 4 ADLs
Apathy
5.86
2.06
(2.97, 11.59)
(1.03,4.14)
7.96 5.21 5.54 1.33
3.49 .89 .68 2.31
*Results of fitting a proportional odds model. tResults of fitting a nonproportional odds model.
Table 5. Predicting Impairment on Individual ADLs Using Best Selected Multiple Logistic Regression Models, Controlling for Age, Sex, Race, and Mental Status (MMSE) (N = 240) Independent Variables Adjusted odds ratios for any difficulty with: Dressing (95% C.I.*) Bathing (95% C.I.) Transferring (95% C.I.) Toileting (95% C.I.) Walking (95% C.I.) Eating (95% C.I.)
Behavioral Disorders
Apathy
n.s.
n.s.t
n.s.
n.s.
8.29 (3.68,18.65) n.s.
(3.24, 17.25) n.s.
n.s. n.s.
Adjusted odds ratios for moderate to severe difficulty with: Dressing 3.03 (95% C.I.) (1.21,7.62) Bathing 3.22 (95% C.I.) (1.26,8.18) Transferring 9.63 (95% C.I.) (4.34,21.33) Toileting 4.66 (95% C.I.) (1.61,13.50) Walking n.s. (95% C.I.) Eating 4.87 (95% C.I.) (1.40, 16.91) *C.I. = confidence interval, tn.s. = not significant.
7.48
2.96 (1.27,6.86) n.s.
n.s. n.s. 4.19 (1.80,9.79) n.s. n.s.
History of Hypertension
n.s. 2.06 (1.00,4.25) n.s. 3.05 (1.27,7.34)
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
Association of multiple clinical symptoms and conditions with functional impairment. — As seen in Table 3, a history of hypertension, the most prevalent physical condition, was significantly associated with the number of ADL impairments (p = .012). The third and fourth most prevalent psychiatric problems, behavioral disorders and apathy, were also significantly associated with the number of ADL impairments (p = .012 and p = .05, respectively). Behavioral disorders had the highest estimated odds ratio (2.16), followed by history of hypertension (1.97) and, finally, apathy (1.84). These adjusted odds ratios, averaged across all cutoff points for the outcome, were estimated from a proportional odds model. The nonproportional odds model then provided a measure of changing magnitude of association with increasing functional impairments. An AD patient with a history of hypertension was about 1.7 times more likely to have one to six ADL impairments compared to a patient of the same age, sex, race, mental status, and the same status for behavioral disorders and apathy, but without a history of hypertension. An AD patient with a history of hypertension was 5.5 times more likely to be impaired on all six ADLs compared to a similar patient without a history. An AD patient with behavioral disorders was 4.5 times more likely to have one or more ADL impairments than a comparable patient without behavioral disorders, and 1.8 times more likely to be impaired on all six ADLs. A patient with apathy was 2.8 times more likely to be impaired on one or more ADLs than a comparable patient without apathy, and 3.2 times more likely to be impaired on all six ADLs. As shown in Table 4, the best model for number of moderate to severe ADL impairments included behavioral disorders (p = .0001) and apathy (p = .042), but not a history of hypertension. A patient with apathy was 3.5 times more likely to have moderate to severe difficulty with any ADL than a comparable patient without apathy; a patient with behavioral disorders was eight times more likely to have moderate to severe difficulty with any ADL compared to a similar patient without behavioral disorders.
FUNCTIONAL STATUS IN AD
tension was associated with impaired toileting and eating. Using only moderate to severe ADL impairment as the outcome, behavioral disorders were associated with impaired dressing, bathing, transferring, toileting, and eating. Apathy was only associated with impairments in transferring. DISCUSSION
out cognitive impairment (8), and an association has been reported between myocardial infarction and the eventual occurrence of AD in very old women (23). Our analysis suggests that myocardial infarction is not related to functional status when AD is already present. Neither the main effect of myocardial infarction nor the interaction between sex and myocardial infarction were significantly associated with ADL impairment. The independent associations of behavioral disorders and apathy with functional status are interesting findings and merit further research. One interpretation is that patients with psychiatric disturbance are more difficult to care for because the behaviors displayed interfere with functional effectiveness. An alternative explanation may relate to the patient's awareness of cognitive deficit and the consequent emotional reaction which may result in behavioral disruption or emotional withdrawal and functional compromise. Yet another is that AD patients with behavioral disorders have selective brain damage and neurotransmitter changes, and that these abnormalities are responsible for ADL impairment rather than the behavioral disorders per se. The works of Zubenko and associates (24-26) indicate that the development of psychosis as well as the development of major depression in AD are each associated with a profile of neurochemical changes qualitatively different from those seen in primary dementia. Depressive moods and symptoms were not independently associated with functional impairment in our study. Further analysis of a subsample of PACT patients for whom Hamilton Depression Rating Scale scores were recorded (n = 163) showed no significant independent association of depression with functional impairment using a cutoff of 23 for severe depression. However, it is still possible that both clinical depression and the presence of depressive mood and other symptoms may be a source of added disability in AD. Pearson and associates (14) reported that AD patients with a diagnosis of major depressive disorder were impaired on IADLs, e.g., handling change, answering the telephone, but not on ADLs. More research is also needed to clarify the extent to which treating depression improves patient functioning. At least one group (15) have reported that imipramine and placebo improved symptoms of depression and functional status in AD patients. Depression as a symptom and apathy can be difficult to distinguish unless there are explicit definitions for classification. The psychiatric examinations at the four sites charted a number of psychiatric signs and symptoms, including depressed mood and other vegetative depressive symptoms, as well as apathy and emotional withdrawal. Research on the nature of apathy may improve our understanding of the patient's experience of Alzheimer's disease as an illness. If apathy is a result of emotional exhaustion in the patient, intensive support should be therapeutic. If apathy is the manifestation of significant emotional withdrawal, environmental and psychosocial stimulation could be helpful. Since depression in dementia can also involve withdrawal and regression, supportive measures such as increased social contacts may also improve function. Although the associations observed should not be interpreted as causal, our results highlight the importance of
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
Little is known about factors related to functional status in patients with AD. The purpose of this study was to determine whether concurrent behavioral and medical problems had an independent association with functional impairment beyond the effect of cognitive impairment. It is important to be cautious about assuming that the observed associations are causal relationships. Longitudinal studies and other experimental data on AD patients are needed in order to address the issue of causality. Indeed, there may be other factors responsible for ADL impairments which are related to these symptoms and conditions. For example, family and psychosocial factors as well as concurrent treatment with antipsychotics, the latter potentially due to dosage as well as side effects, may be related to impaired functioning. Drug use data and psychosocial and family variables are currently being analyzed in relation to patient clinical status. Our results showing an independent association of the MMSE score with ADL impairment, including moderate to severe ADL impairment, are consistent with the findings of Vitaliano and colleagues (22) and Pearson and colleagues (14). However, this is perhaps the first study testing the independent association of multiple coexisting medical and behavioral problems with diminished ADLs beyond the effects of cognitive impairment attributable to AD. It is not clear why more physical problems were not associated with functional impairment. One explanation is that certain chronic conditions known to have a significant impact on function, e.g., hip fracture and osteoporosis, were not evaluated because they were not listed on the case enrollment form as part of the physical examination and medical history. Another possible explanation is that the presence of cognitive impairment has a powerful main effect where the loss of cognitive capacities compromises overall self-care abilities more than physical conditions and comorbidities. Hypertension, the most prevalent medical problem by history, was independently associated with any functional impairment but not with moderate to severe functional impairment. There are several possible explanations for the association. All patient blood pressure values were normal in our sample at the time of their examination, indicating that the high blood pressure was controlled. However, patients with a history of hypertension might have undetected white matter disease complicating their primary dementia. Another explanation is that drugs used to treat the hypertension, e.g., diuretics, may also have affected performance on ADLs. This interpretation may help explain the observation that hypertension was more highly associated with toileting problems than any other ADL. The possible effects of a history of high blood pressure or drug treatment effects on functioning are worthy of further study. Cardiovascular disease has been reported to have a significant impact on functional impairment in older persons with-
M181
M182
FREELS ET AL.
treating behavioral problems in AD. Management of psychiatric problems, which is often difficult in AD patients, may maximize well-being and overall functional effectiveness in the patient as well as the caregivers. The co-occurrence of both agitation and depressive symptoms was significantly associated with functional impairment in a simple bivariate analysis, but these symptoms did not emerge as significant in the multivariate model. It remains to be determined whether interventions to reduce or eliminate these symptoms and others will further improve functional effectiveness. We have a great deal to learn about maximizing functional effectiveness or reducing excess disability in AD patients. ACKNOWLEDGMENTS
11.
12.
13.
14.
15.
Address correspondence and reprint requests to Dr. Sally Freels, School of Public Health, Biostatistics Program, University of Illinois at Chicago, 2121 West Taylor M/C 922, Chicago, IL 60680-6998.
REFERENCES
1. Alzheimer A. Uber eimemartige Erkrankung der Hirurinde. Allgemeine Zeitschrift fur Psychiatric und Psychisch-Gerichtliche Medicine. 1907 ;64:146-8. 2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 3rd ed., rev. Washington, DC: Author, 1987. 3. Wragg RE, Jeste DV. Overview of depression and psychosis in Alzheimer's disease. Am J Psychiatry 1989; 146:577-87. 4. Eisdorfer C, Cohen D, Paveza G, Ashford W, Luchins D, Gorelick P, Hirschman R, Freels S, Levy P, Semla T, Shaw H. An empirical evaluation of the global deterioration scale for staging Alzheimer's disease. Am J Psychiatry 1992; 149:190-4. 5. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDSADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1986,34:939^4. 6. Eisdorfer C, Cohen D. Management of the patient and family with dementing illness. J Fam Prac 1981; 12:831-7. 7. Volicer L, Fabiszewski KS, Rheaume YL, Lasch KE. Clinical management of Alzheimer's disease. Rockville, MD: Aspen, 1988. 8. Verbrugge L, Lepkowski J, Imanada Y. Co-morbidity and its impact on disability. Milbank Q 1989;67:45O-85. 9. Verbrugge LM, Lepkowski J, Konkol LL. Levels of disability among U.S. adults with arthritis. J Gerontol Social Sci 1991 ;46:S71-83. 10. Lowenstein DA, Amigo E, Duara R, Guterman A, Hurwitz D, Berkowitz N, Wilkie F, Weinberg G, Black B, Gittelman B, Eisdorfer C. A
16. 17.
18.
19. 20. 21.
22.
23.
24.
25. 26.
Received September 27', 1991 Accepted January 14, 1992
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
This research was supported in part by NIA grant 5U0I AG06777 to Dr. Cohen.
new scale for the assessment of functional status in Alzheimer's disease and related disorders. J Gerontol Psych Sci 1989;44:P114-21. Mahurin RK, DeBettignies BH, Pirozzolo FJ. Structured assessment of independent living skills: preliminary report of a performance measure of functional abilities in dementia. J Gerontol Psych Sci 1991; 46:P58-66. U.S. Department of Health and Human Services. Consensus Development Conference statement: geriatric assessment methods for clinical decision-making (October 19-21). Bethesda, MD: Author, 1987. Cohen D, Paveza G, Eisdorfer C, Gorelick P, Luchins D, Hirschman R, Ashford W. Morbidity and co-morbidity in patients with Alzheimer's disease (AD): results from a large-scale patient registry. Presented at the Annual Meeting of the Gerontological Society of America, Minneapolis, November 1989. Pearson JL, Teri L, Reifler BV, Raskind MA. Functional status and cognitive impairment in Alzhiemer's patients with and without depression. J Am Geriatr Soc 1989;37:1117-21. Reifler BV, Teri L, Raskind M, Veith R, Barnes R, White E, McLean P. Double-blind trial of imipramine in Alzheimer's patients with and without depression. Am J Psychiatry 1989; 146:45-9. Reifler BV, Larson E, Teri L, Poulsen M. Dementia of the Alzheimer's type and depression. J Am Geriatr Soc 1986;34:855-9. Cohen D, Paveza G, Levy PS, Ashford W, Brody JA, Eisdorfer C, Gorelick P, Hirschman R, Luchins D, Trozzolo T, Shaw H. An Alzheimer's disease patient registry: the Prototype Alzheimer Collaborative Team (PACT). Aging 1990;2:312-6. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method of grading the cognitive state of patients for the clinician. J PsychiatrRes 1975; 12:189-98. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62. Hosmer D, Lemeshow S. Applied logistic regression. New York: John Wiley & Sons, 1989. Peterson B, Harrell FE. Partial proportional odds models and the logist procedure. Proceedings of the Thirteenth Annual SAS Users Group International Conference, March 27-30. Cary, NC: SAS Institute Inc., 1988:952-6. Vitaliano PP, Breen AR, Albert MS. Memory, attention, and functional status in community-residing Alzheimer type dementia patients and optimally healthy aged individuals. J Gerontol 1984;39:58—64. Aronson MK, Ooi WL, Morgenstern H, Hafner A, Masur D, Crystal H, Frishman W, Fisher D, Katzman R. Women, myocardial infarction, and dementia in the very old. Neurology I99O;40:1102-6. Zubenko GS, Moossy J, Martinez AJ, Rao G, Classen D, Rosen J, Kopp U. Neuropathologic and neurochemical correlates of psychosis in primary dementia. Arch Neurol 1991 ;48:619-24. Zubenko GS, Moossy J, Kopp U. Neurochemical correlates of major depression in primary dementia. Arch Neurol 1990;47:209-14. Rosen J, Zubenko GS. Emergence of psychosis and depression in the longitudinal evaluation of Alzheimer's disease. Biol Psychol 1991; 29:224-32.
Copyright 1992 by The Geronlological Society of America
Functional Status and Clinical Findings in Patients With Alzheimer's Disease Sally Freds, 1 Donna Cohen,3 Carl Eisdorfer,4 Gregory Paveza,1 Philip Gorelick,5 Daniel J. Luchins,6 Robert Hirschman,7 J. Wesson Ashford,8 Paul Levy,1 Todd Semla,2 and Helen Shaw1
We analyzed the association of clinical findings with impaired functional status, i.e., activities of daily living (ADLs), in a sample of 240 patients diagnosed with Alzheimer's disease by NINCDSIADRDA or DSM-I1I-R criteria. Logistic regression models were used to determine independent predictors of both the number of ADL impairments and number of ADL impairments characterized as moderate to severe. Two psychiatric problems, behavioral disorders and apathy, as well as a history of hypertension were significantly associated with ADL impairment independent of age, sex, race, and cognitive impairment. Behavioral disorders and apathy were also significantly associated with moderate to severe ADL impairment, but hypertension was not significant at this level.
A LZHEIMER'S disease (AD) is characterized by a pro* * • gressive loss of cognitive and functional capacities as well as neuropsychiatric problems (1-5). At present, the course of the disease cannot be reversed, and until effective treatments are available, clinical management strategies will continue to focus on maximizing health and functional effectiveness as well as emotional well-being (6,7). Because medical problems can have a major impact on the way older persons carry out basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs) (8,9), it is reasonable to assume that health problems are also related to the daily life activities of individuals with AD. Cognitive impairment is related to diminished functional status in AD (10-13), but it is not known to what extent the coexistence of cognitive impairment with other physical, psychiatric, or neurologic problems is associated with functional impairment. At least one study (14) has demonstrated the independent effects of the presence of clinical depression on the performance of I ADLs, but not ADLs, in AD patients. A few studies have also shown that interventions targeting comorbid or coexisting conditions have reduced patient discomfort and improved functioning (15,16). To our knowledge, no study has investigated the association of concurrent psychiatric and neurologic signs and symptoms as well as physical conditions with functional impairment in AD patients. This article reports the prevalence of the most common coexisting clinical symptoms and conditions and analyzes their independent associations with functional status. We hypothesized that the most prevalent coexisting clinical conditions and symptoms would be related to decreased functional status as measured by ADL
impairments beyond the effect of the cognitive loss directly attributable to AD. METHODS
Data set. — The 240 subjects in this study were selected from an Alzheimer's Disease Patient Registry known as the Prototype Alzheimer's Collaborative Team (PACT). PACT was established to study the feasibility and costs of establishing and operating a large-scale multisite registry for research on AD and other dementias. Methods and procedures for case ascertainment and enrollment as well as data management have been described (17), and several methodological papers are being written. Briefly, PACT consists of a Data Coordinating and Analysis Center at the University of Illinois at Chicago which registered patients evaluated and diagnosed at six medical sites: the Memory Disorders Clinic at the Mount Sinai Medical Center, Miami Beach; the Memory Disorders Clinic at the University of Miami Jackson Memorial Hospital; the Geriatrics Institute, University of Wisconsin-Milwaukee Clinical Campus; the Regional Alzheimer's Disease Center, Southern Illinois University School of Medicine; the Alzheimer's Disease Center, Michael Reese Hospital and Medical Center; and the University of Chicago School of Medicine Geriatric Clinic. Four of the six sites evaluated dementia patients using their own standardized protocols for psychiatric, neurological, physical, psychological, and psychosocial examinations of patients by an interdisciplinary medical team. The remaining two sites used dementia protocols, but patients were not evaluated by an interdisciplinary team. M177
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
'School of Public Health and 2College of Pharmacy, University of Illinois at Chicago, department of Aging and Mental Health, University of Southern Florida, Tampa. "Department of Psychiatry, University of Miami. 5 Department of Neurology, Rush-Presbyterian-St. Luke's Medical Center, Chicago. "Department of Psychiatry, University of Chicago. 'Department of Psychiatry, University of Wisconsin-Milwaukee. 'Department of Psychiatry, VA Medical Center, Martinez, California.
M178
FREELSETAL.
Variables. —The variables used in this analysis were four sets of measures from the PACT case enrollment form: sociodemographic information, i.e., age, race, and sex; results of the psychiatric, neurologic, and physical examinations by respective specialists at the PACT centers; ratings of functional status by the psychiatrist on six ADLs; and MiniMental State Examination (MMSE) test scores. The results of psychiatric, neurologic, and physical examinations were coded to note the presence or absence of specific conditions, signs, and symptoms observed during the multidisciplinary evaluation of the patient's dementia. Missing or unclear items were coded as unknown, but only patients with complete data, i.e., no unknown values, were used in this analysis. The possible range of signs and symptoms recorded after psychiatric interviews included agitation, depressed mood and other depressive symptoms, apathy (i.e., absence of emotion or emotional withdrawal), insomnia, behavioral disorders (e.g., screaming, wandering, catastrophic reactions, aggressivity), hallucinations, paranoia, delusions, and emotional lability. Psychiatrists examining patients at each site recorded symptoms as present or absent on a dementia interview protocol and also administered a Hamilton Depression Rating Scale (19). The possible range of symptoms recorded from neurologic examinations included agnosia, aphasia, apraxia, dizziness, dysarthria, dysphoria, gait problems, headache, paresthesia, seizures, weakness (upper and lower motor neuron), extrapyramidal signs (not due to drugs), abnormal muscle stretch reflex, presence of glabellar, suck, snout, or Babinski reflexes, and alterations in sensation. Neurologists examining patients at each site recorded signs and symptoms on a dementia examination protocol. Acute and chronic conditions documented after a physical examination and medical history included myocardial in-
farction or chronic cardiovascular disease; hypertension or history of hypertension; chronic renal, hepatic, pulmonary, or endocrine disease; history of stroke; hypoglycemia; diabetes; thyroid disorders; severe visual and hearing impairment; alcoholism or substance abuse; and tremors not due to drugs. Functional status included ratings of impairment on six ADLs — dressing, bathing, eating, walking, transferring, and toileting — at the time of evaluation or diagnosis. Patients were rated using a 4-point scale: 1 = able to do easily, 2 = has some difficulty, 3 = has great difficulty, and 4 = unable to do ADL. For the analyses, ratings were dichotomized two ways: to reflect whether or not there was any ADL impairment (grouping categories 2-4 vs 1), and to reflect whether or not there was moderate to severe impairment on ADLs (grouping categories 1-2 vs 3-4). For each coding scheme, ADL impairment ratings were added together to produce two summary scores reflecting functional status: number of ADL impairments and number of ADL impairments characterized as moderate to severe. Data analysis. —Multiple logistic regression was used to test the associations of clinical symptoms and conditions with ADL impairment independent of age, sex, race, cognitive impairment, and other significant conditions and symptoms. Only those symptoms and conditions appearing in 10% or more of the sample were selected for analysis. Logistic regression for ordered categorical outcomes (20) was used to analyze the number of ADL impairments, ranging from zero to six, as a dependent variable; symptoms, conditions, and other covariates were used as independent variables. Two models are available for ordered outcomes: proportional odds and nonproportional odds (21). Under the proportional odds model, odds ratios for the effect of each independent variable are assumed to be equal across different cutoff points. For example, if severe visual impairment were found to be significantly associated with the number of ADL impairments, the proportional odds model posits that the relative odds of having one or more ADL impairments (for patients with severe visual impairment compared to patients without) is equal to the relative odds of having two or more, three or more, and so on. The nonproportional odds model, on the other hand, includes additional parameters allowing estimates of different odds ratios for different cutoff points in the outcome. The advantage of the nonproportional odds model is that estimates of different odds ratios for different cutoff points provide a good description of changing magnitudes of associations with increasing functional impairment. The disadvantage is that the extra degrees of freedom used to estimate additional parameters result in less powerful tests of the overall effect of each condition or symptom. For this reason, the nonproportional odds model was used for variable selection. A forward stepwise selection procedure was used to select the best combination of symptoms and conditions associated with functional status, controlling for age, sex, race, and MMSE score, with a proportional odds multiple logistic regression equation. A nonproportional odds model was also fit for the variables in the final selected model in order to estimate different odds ratios under different cutoff points
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
PACT contains diagnostic, psychosocial, and sociodemographic data on a total of 1,402 persons with Alzheimer's disease, multi-infarct dementia, or related disorders from the six sites. A sociodemographic profile of the registry population has been published elsewhere (17), and comparisons of cases across centers are being analyzed. In order to be enrolled in PACT, patients had to be 40 years or older, living in the community at the time of diagnosis, and diagnosed between 1987 and 1989. The 240 cases selected for this analysis met three criteria. Subjects first had to have a diagnosis of probable or possible Alzheimer's disease by NINCDS-ADRDA criteria (5), Alzheimer's disease by DSM-III-R criteria (2), or primary degenerative dementia of the Alzheimer type by DMS-III-R criteria (2) (n = 671). Second, registry files had to have complete information documenting the results of physical, neurologic, and psychiatric examinations, including ratings of functional status by a multidisciplinary team (n = 348). Finally, a Mini-Mental State Examination (MMSE) score using the full 30-point Folstein instrument (18) had to be recorded (n = 240). The 240 cases analyzed here come from the four sites where the multidisciplinary evaluation included independent examinations by an internist, neurologist, psychiatrist, and psychologist as well as a social worker.
FUNCTIONAL STATUS IN AD
M179
Table 1. Prevalence of ADL Impairments (N = 240) Any Impairment Number of ADL Impairments
Number of Patients 100 43 36 17 24 9 11
Moderate to Severe Impairment Percent of Patients
Number of ADL Impairments
41.7%
163 43 10 11 6 3 4
17.9 15.0 7.1 10.0 3.8 4.6
Any Impairment Individual ADLs
89 80 80 53 37 34
Percent of Patients 67.9% 17.9 4.2 4.6 2.5 1.2 1.7
Moderate to Severe Impairment Percent of Patients 37.1% 33.3 33.3 22.1 15.4 14.2
for the number of ADL impairments. Finally, the set of independent variables selected were fit to binary logistic regression models predicting each ADL separately. RESULTS
The average age of the AD patients was 74.5 (SD = 7.8) years with a M/F sex ratio of 0.6. The average MMSE score was 15.5 (SD = 7.4). A score of 21 marked the 75th percentile and a score of 9 marked the 25th percentile of the distribution of patient scores. The average duration of dementia from the earliest onset of dementia symptoms to evaluation or diagnosis at the enrolling clinical center was 3.4 years (SD = 2.6). The case enrollment form contained the month and year of diagnosis or evaluation at the center, the month and year of reported earliest onset of dementia, as well as a checklist of possible symptoms reported to mark the onset of dementia, e.g., language difficulties, confusion, difficulties at work, and social occasions or with family. Prevalence offunctional impairment. — The distribution of the number of ADL impairments and the prevalence of each ADL impairment are reported in Table 1. A total of 58.3% of the sample was impaired on one or more ADLs, with over half of this subset (32.9%) impaired on one or two ADLs and the rest impaired on three or more ADLs. Of the sample, 32.1 % had moderate to severe impairment on one or more ADLs. The most prevalent ADL impairments were dressing (37.1% had any impairment; 12.9% had moderate to severe impairment), bathing (33.3% had any impairment; 11.7% had moderate to severe impairment), and transferring (33.3% had any impairment; 22.9% had moderate to severe impairment). Prevalence of clinical symptoms and conditions. — Table 2 reports the observed prevalence of psychiatric and neurologic signs and symptoms as well as acute and chronic physical conditions occurring in 10% or more of the sample
Individual ADLs Dressing Bathing Transferring Toileting Walking Eating
Number of Patients 31 28 55 21 9 15
Percent of Patients 12.9% 11.7 22.9 8.8 3.8 6.3
Table 2. Prevalence of Clinical Symptoms and Conditions (N = 240) Number of Patients
Percent of Patients
Psychiatric Symptoms: Agitation Depressive symptoms Behavioral disorders Apathy Insomnia Delusions Paranoia Hallucinations
72 65 52 48 37 27 26 25
30.0% 27.1 21.7 20.0 15.4 11.3 10.8 10.4
Neurologic Symptoms: Apraxia Dysphoria Aphasia Alteration in sensations
56 50 32 24
23.3 20.8 13.3 10.0
Physical Conditions: History of hypertension MI or cardiovascular disease Severe visual impairment Thyroid disorder
76 47 29 24
31.7 19.6 12.1 10.0
at the time of diagnosis or evaluation at the PACT center. The four most common psychiatric problems were agitation (30.0%), depressive mood and symptoms (27.1%), behavioral disorders (21.7%), and apathy (20.0%). Agitation cooccurred with depression in 14.2% of patients, with behavioral disorders in 11.2% of patients and with apathy in 12.1% of patients. The most prevalent reported neurologic symptom was apraxia (23.3%). The most common physical conditions were a history of hypertension (31.7%) and a history of myocardial infarction/chronic cardiovascular disease (19.6%), which also occurred together in 7.1% of the sample.
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
Dressing Bathing Transferring Toileting Walking Eating
Number of Patients
Number of Patients
FREELSETAL.
M180
Table 3. Best Selected Multiple Logistic Regression Model Predicting Functional Status (Number of ADL Impairments) Controlling for Age, Sex, Race, and Mental Status (MMSE) (N = 240) Independent Variables
Behavioral Disorders
Apathy
History of Hypertension
Adjusted odds ratios*
2.16
1.84
1.97
(1.18,3.93)
(1.00,3.37)
(1.16,3.34)
(95% confidence intervals) Adjusted odds ratiost for any difficulty with: s= 1 ADLs vs = 0 ADLs 55 2 ADLs vs < 2 ADLs ss 3 ADLs vs < 3 ADLs & 4 ADLs vs < 4 ADLs 5* 5 ADLs vs < 5 ADLs 6 ADLs vs < 6 ADLs
4.52 1.52 2.54 1.59 1.71 1.83
2.76 1.57 1.39 1.32 2.18 3.19
*Results of fitting a proportional odds model. tResults of fitting a nonproportional odds model.
1.72 2.04 1.81 2.21 2.92 5.46
The results of fitting multiple logistic regression models with individual ADL impairments as the dependent variable are shown in Table 5. Defining ADL impairment as having any difficulty, behavioral disorders were associated with impairments in transferring; apathy was associated with impairments in transferring and walking; and a history of hyperTable 4. Best Selected Multiple Logistic Regression Model Predicting Functional Status (Number of Moderate to Severe ADL Impairments) Controlling for Age, Sex, Race, and Mental Status (MMSE) (N = 240) Behavioral Disorders
Independent Variables Adjusted odds ratios* (95% confidence intervals) Adjusted odds ratiost for moderate to severe difficulty with: S3 1 ADLs vs = 0 ADLs S3 2 ADLs vs < 2 ADLs S3 3 ADLs vs < 3 ADLs ss 4 ADLs vs < 4 ADLs
Apathy
5.86
2.06
(2.97, 11.59)
(1.03,4.14)
7.96 5.21 5.54 1.33
3.49 .89 .68 2.31
*Results of fitting a proportional odds model. tResults of fitting a nonproportional odds model.
Table 5. Predicting Impairment on Individual ADLs Using Best Selected Multiple Logistic Regression Models, Controlling for Age, Sex, Race, and Mental Status (MMSE) (N = 240) Independent Variables Adjusted odds ratios for any difficulty with: Dressing (95% C.I.*) Bathing (95% C.I.) Transferring (95% C.I.) Toileting (95% C.I.) Walking (95% C.I.) Eating (95% C.I.)
Behavioral Disorders
Apathy
n.s.
n.s.t
n.s.
n.s.
8.29 (3.68,18.65) n.s.
(3.24, 17.25) n.s.
n.s. n.s.
Adjusted odds ratios for moderate to severe difficulty with: Dressing 3.03 (95% C.I.) (1.21,7.62) Bathing 3.22 (95% C.I.) (1.26,8.18) Transferring 9.63 (95% C.I.) (4.34,21.33) Toileting 4.66 (95% C.I.) (1.61,13.50) Walking n.s. (95% C.I.) Eating 4.87 (95% C.I.) (1.40, 16.91) *C.I. = confidence interval, tn.s. = not significant.
7.48
2.96 (1.27,6.86) n.s.
n.s. n.s. 4.19 (1.80,9.79) n.s. n.s.
History of Hypertension
n.s. 2.06 (1.00,4.25) n.s. 3.05 (1.27,7.34)
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
Association of multiple clinical symptoms and conditions with functional impairment. — As seen in Table 3, a history of hypertension, the most prevalent physical condition, was significantly associated with the number of ADL impairments (p = .012). The third and fourth most prevalent psychiatric problems, behavioral disorders and apathy, were also significantly associated with the number of ADL impairments (p = .012 and p = .05, respectively). Behavioral disorders had the highest estimated odds ratio (2.16), followed by history of hypertension (1.97) and, finally, apathy (1.84). These adjusted odds ratios, averaged across all cutoff points for the outcome, were estimated from a proportional odds model. The nonproportional odds model then provided a measure of changing magnitude of association with increasing functional impairments. An AD patient with a history of hypertension was about 1.7 times more likely to have one to six ADL impairments compared to a patient of the same age, sex, race, mental status, and the same status for behavioral disorders and apathy, but without a history of hypertension. An AD patient with a history of hypertension was 5.5 times more likely to be impaired on all six ADLs compared to a similar patient without a history. An AD patient with behavioral disorders was 4.5 times more likely to have one or more ADL impairments than a comparable patient without behavioral disorders, and 1.8 times more likely to be impaired on all six ADLs. A patient with apathy was 2.8 times more likely to be impaired on one or more ADLs than a comparable patient without apathy, and 3.2 times more likely to be impaired on all six ADLs. As shown in Table 4, the best model for number of moderate to severe ADL impairments included behavioral disorders (p = .0001) and apathy (p = .042), but not a history of hypertension. A patient with apathy was 3.5 times more likely to have moderate to severe difficulty with any ADL than a comparable patient without apathy; a patient with behavioral disorders was eight times more likely to have moderate to severe difficulty with any ADL compared to a similar patient without behavioral disorders.
FUNCTIONAL STATUS IN AD
tension was associated with impaired toileting and eating. Using only moderate to severe ADL impairment as the outcome, behavioral disorders were associated with impaired dressing, bathing, transferring, toileting, and eating. Apathy was only associated with impairments in transferring. DISCUSSION
out cognitive impairment (8), and an association has been reported between myocardial infarction and the eventual occurrence of AD in very old women (23). Our analysis suggests that myocardial infarction is not related to functional status when AD is already present. Neither the main effect of myocardial infarction nor the interaction between sex and myocardial infarction were significantly associated with ADL impairment. The independent associations of behavioral disorders and apathy with functional status are interesting findings and merit further research. One interpretation is that patients with psychiatric disturbance are more difficult to care for because the behaviors displayed interfere with functional effectiveness. An alternative explanation may relate to the patient's awareness of cognitive deficit and the consequent emotional reaction which may result in behavioral disruption or emotional withdrawal and functional compromise. Yet another is that AD patients with behavioral disorders have selective brain damage and neurotransmitter changes, and that these abnormalities are responsible for ADL impairment rather than the behavioral disorders per se. The works of Zubenko and associates (24-26) indicate that the development of psychosis as well as the development of major depression in AD are each associated with a profile of neurochemical changes qualitatively different from those seen in primary dementia. Depressive moods and symptoms were not independently associated with functional impairment in our study. Further analysis of a subsample of PACT patients for whom Hamilton Depression Rating Scale scores were recorded (n = 163) showed no significant independent association of depression with functional impairment using a cutoff of 23 for severe depression. However, it is still possible that both clinical depression and the presence of depressive mood and other symptoms may be a source of added disability in AD. Pearson and associates (14) reported that AD patients with a diagnosis of major depressive disorder were impaired on IADLs, e.g., handling change, answering the telephone, but not on ADLs. More research is also needed to clarify the extent to which treating depression improves patient functioning. At least one group (15) have reported that imipramine and placebo improved symptoms of depression and functional status in AD patients. Depression as a symptom and apathy can be difficult to distinguish unless there are explicit definitions for classification. The psychiatric examinations at the four sites charted a number of psychiatric signs and symptoms, including depressed mood and other vegetative depressive symptoms, as well as apathy and emotional withdrawal. Research on the nature of apathy may improve our understanding of the patient's experience of Alzheimer's disease as an illness. If apathy is a result of emotional exhaustion in the patient, intensive support should be therapeutic. If apathy is the manifestation of significant emotional withdrawal, environmental and psychosocial stimulation could be helpful. Since depression in dementia can also involve withdrawal and regression, supportive measures such as increased social contacts may also improve function. Although the associations observed should not be interpreted as causal, our results highlight the importance of
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
Little is known about factors related to functional status in patients with AD. The purpose of this study was to determine whether concurrent behavioral and medical problems had an independent association with functional impairment beyond the effect of cognitive impairment. It is important to be cautious about assuming that the observed associations are causal relationships. Longitudinal studies and other experimental data on AD patients are needed in order to address the issue of causality. Indeed, there may be other factors responsible for ADL impairments which are related to these symptoms and conditions. For example, family and psychosocial factors as well as concurrent treatment with antipsychotics, the latter potentially due to dosage as well as side effects, may be related to impaired functioning. Drug use data and psychosocial and family variables are currently being analyzed in relation to patient clinical status. Our results showing an independent association of the MMSE score with ADL impairment, including moderate to severe ADL impairment, are consistent with the findings of Vitaliano and colleagues (22) and Pearson and colleagues (14). However, this is perhaps the first study testing the independent association of multiple coexisting medical and behavioral problems with diminished ADLs beyond the effects of cognitive impairment attributable to AD. It is not clear why more physical problems were not associated with functional impairment. One explanation is that certain chronic conditions known to have a significant impact on function, e.g., hip fracture and osteoporosis, were not evaluated because they were not listed on the case enrollment form as part of the physical examination and medical history. Another possible explanation is that the presence of cognitive impairment has a powerful main effect where the loss of cognitive capacities compromises overall self-care abilities more than physical conditions and comorbidities. Hypertension, the most prevalent medical problem by history, was independently associated with any functional impairment but not with moderate to severe functional impairment. There are several possible explanations for the association. All patient blood pressure values were normal in our sample at the time of their examination, indicating that the high blood pressure was controlled. However, patients with a history of hypertension might have undetected white matter disease complicating their primary dementia. Another explanation is that drugs used to treat the hypertension, e.g., diuretics, may also have affected performance on ADLs. This interpretation may help explain the observation that hypertension was more highly associated with toileting problems than any other ADL. The possible effects of a history of high blood pressure or drug treatment effects on functioning are worthy of further study. Cardiovascular disease has been reported to have a significant impact on functional impairment in older persons with-
M181
M182
FREELS ET AL.
treating behavioral problems in AD. Management of psychiatric problems, which is often difficult in AD patients, may maximize well-being and overall functional effectiveness in the patient as well as the caregivers. The co-occurrence of both agitation and depressive symptoms was significantly associated with functional impairment in a simple bivariate analysis, but these symptoms did not emerge as significant in the multivariate model. It remains to be determined whether interventions to reduce or eliminate these symptoms and others will further improve functional effectiveness. We have a great deal to learn about maximizing functional effectiveness or reducing excess disability in AD patients. ACKNOWLEDGMENTS
11.
12.
13.
14.
15.
Address correspondence and reprint requests to Dr. Sally Freels, School of Public Health, Biostatistics Program, University of Illinois at Chicago, 2121 West Taylor M/C 922, Chicago, IL 60680-6998.
REFERENCES
1. Alzheimer A. Uber eimemartige Erkrankung der Hirurinde. Allgemeine Zeitschrift fur Psychiatric und Psychisch-Gerichtliche Medicine. 1907 ;64:146-8. 2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 3rd ed., rev. Washington, DC: Author, 1987. 3. Wragg RE, Jeste DV. Overview of depression and psychosis in Alzheimer's disease. Am J Psychiatry 1989; 146:577-87. 4. Eisdorfer C, Cohen D, Paveza G, Ashford W, Luchins D, Gorelick P, Hirschman R, Freels S, Levy P, Semla T, Shaw H. An empirical evaluation of the global deterioration scale for staging Alzheimer's disease. Am J Psychiatry 1992; 149:190-4. 5. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDSADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1986,34:939^4. 6. Eisdorfer C, Cohen D. Management of the patient and family with dementing illness. J Fam Prac 1981; 12:831-7. 7. Volicer L, Fabiszewski KS, Rheaume YL, Lasch KE. Clinical management of Alzheimer's disease. Rockville, MD: Aspen, 1988. 8. Verbrugge L, Lepkowski J, Imanada Y. Co-morbidity and its impact on disability. Milbank Q 1989;67:45O-85. 9. Verbrugge LM, Lepkowski J, Konkol LL. Levels of disability among U.S. adults with arthritis. J Gerontol Social Sci 1991 ;46:S71-83. 10. Lowenstein DA, Amigo E, Duara R, Guterman A, Hurwitz D, Berkowitz N, Wilkie F, Weinberg G, Black B, Gittelman B, Eisdorfer C. A
16. 17.
18.
19. 20. 21.
22.
23.
24.
25. 26.
Received September 27', 1991 Accepted January 14, 1992
Downloaded from http://geronj.oxfordjournals.org/ at New York University on June 24, 2015
This research was supported in part by NIA grant 5U0I AG06777 to Dr. Cohen.
new scale for the assessment of functional status in Alzheimer's disease and related disorders. J Gerontol Psych Sci 1989;44:P114-21. Mahurin RK, DeBettignies BH, Pirozzolo FJ. Structured assessment of independent living skills: preliminary report of a performance measure of functional abilities in dementia. J Gerontol Psych Sci 1991; 46:P58-66. U.S. Department of Health and Human Services. Consensus Development Conference statement: geriatric assessment methods for clinical decision-making (October 19-21). Bethesda, MD: Author, 1987. Cohen D, Paveza G, Eisdorfer C, Gorelick P, Luchins D, Hirschman R, Ashford W. Morbidity and co-morbidity in patients with Alzheimer's disease (AD): results from a large-scale patient registry. Presented at the Annual Meeting of the Gerontological Society of America, Minneapolis, November 1989. Pearson JL, Teri L, Reifler BV, Raskind MA. Functional status and cognitive impairment in Alzhiemer's patients with and without depression. J Am Geriatr Soc 1989;37:1117-21. Reifler BV, Teri L, Raskind M, Veith R, Barnes R, White E, McLean P. Double-blind trial of imipramine in Alzheimer's patients with and without depression. Am J Psychiatry 1989; 146:45-9. Reifler BV, Larson E, Teri L, Poulsen M. Dementia of the Alzheimer's type and depression. J Am Geriatr Soc 1986;34:855-9. Cohen D, Paveza G, Levy PS, Ashford W, Brody JA, Eisdorfer C, Gorelick P, Hirschman R, Luchins D, Trozzolo T, Shaw H. An Alzheimer's disease patient registry: the Prototype Alzheimer Collaborative Team (PACT). Aging 1990;2:312-6. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method of grading the cognitive state of patients for the clinician. J PsychiatrRes 1975; 12:189-98. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62. Hosmer D, Lemeshow S. Applied logistic regression. New York: John Wiley & Sons, 1989. Peterson B, Harrell FE. Partial proportional odds models and the logist procedure. Proceedings of the Thirteenth Annual SAS Users Group International Conference, March 27-30. Cary, NC: SAS Institute Inc., 1988:952-6. Vitaliano PP, Breen AR, Albert MS. Memory, attention, and functional status in community-residing Alzheimer type dementia patients and optimally healthy aged individuals. J Gerontol 1984;39:58—64. Aronson MK, Ooi WL, Morgenstern H, Hafner A, Masur D, Crystal H, Frishman W, Fisher D, Katzman R. Women, myocardial infarction, and dementia in the very old. Neurology I99O;40:1102-6. Zubenko GS, Moossy J, Martinez AJ, Rao G, Classen D, Rosen J, Kopp U. Neuropathologic and neurochemical correlates of psychosis in primary dementia. Arch Neurol 1991 ;48:619-24. Zubenko GS, Moossy J, Kopp U. Neurochemical correlates of major depression in primary dementia. Arch Neurol 1990;47:209-14. Rosen J, Zubenko GS. Emergence of psychosis and depression in the longitudinal evaluation of Alzheimer's disease. Biol Psychol 1991; 29:224-32.
