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Journal of Gerontology: MEDICAL SCIENCES The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. Cite journal as: J Gerontol A Biol Sci Med Sci All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org. 2010 Vol. 65A, No. 4, 434 441 Advance Access published on December 17, 2009 doi:10.1093/gerona/glp197 Differences in Functional Impairment Across Subtypes of Dementia Tanya Ruff Gure, 1 Mohammed U. Kabeto, 2 Brenda L. Plassman, 3 John D. Piette, 3,4 and Kenneth M. Langa 3,4 Divisions of 1 Geriatric Medicine and 2 General Internal Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor. 3 Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina. 4 Department of Veterans Affairs, VA Center for Practice Management & Outcomes Research, VA Ann Arbor Healthcare System, Michigan. Dementia is characterized by significant declines in cognitive and physical functioning and is a leading cause of disability in later life. Despite the importance of functional status to the diagnosis of dementia, there is currently limited information on differences in functional limitations across subgroups of patients that differ in their dementia etiology. An improved understanding of functional profiles for older adults with dementia could play a role in the effective design of community-based programs that address the growing epidemic of this disease. High-quality, community-based, and institutional services are increasingly needed for patients with dementia to lessen its impact on individuals, families, and the health care system. More specific information on the likely functional needs of dementia patients could also be helpful to clinicians, in particular primary care physicians, in accurately predicting which patients will be able to live independently and safely. 434 Address correspondence to Tanya Ruff Gure, MD, Division of Geriatric Medicine, University of Michigan, Ann Arbor, MI. Email: tanruff@med.umich.edu Background. Dementia is a cause of disability in later life. Despite the importance of functional status to the diagnosis of dementia, limited information exists on differences in functional limitations by dementia subtype. We conducted a cross-sectional analysis using the Aging, Demographics, and Memory Study (ADAMS) to determine the extent of functional impairment among older adults with dementia due to different etiologies. Methods. The ADAMS sample consisted of 856 individuals aged 71 years and older originally surveyed as part of the Health and Retirement Study. Based on a comprehensive in-person cognitive evaluation, respondents were assigned to diagnostic categories of normal cognition, cognitive impairment not demented, and demented. Dementia subtypes were grouped into three categories: vascular dementia (VaD), Alzheimer s dementia (AD), and dementia due to other etiologies. For 744 of the 856 respondents, a proxy informant completed a questionnaire asking whether the respondent had difficulty completing instrumental activities of daily living and activities of daily living (ADLs). Results. Of 744 ADAMS participants, 263 had dementia: 199 (70.5%) with AD, 42 (16.9%) with VaD, and 22 (12.6%) were demented due to other etiologies. After adjustment for demographics, chronic illnesses, and dementia severity, participants with VaD (odds ratio [OR] 5.74; 95% confidence interval [CI] 2.60 12.69) and other etiologies of dementia (OR 21.23; 95% CI 7.25 62.16) were more likely to have greater than or equal to four ADL limitations compared with those with AD. Conclusions. VaD is associated with significantly more ADL limitations than AD. These physical limitations should be considered when designing adult day care programs, which adequately accommodate the needs of non-ad patients. Key Words: Activities of daily living Instrumental activities of daily living Disability Dementia. Received August 21, 2009; Accepted November 12, 2009 Decision Editor: Luigi Ferrucci, MD, PhD There are some clinical features that distinguish Alzheimer s disease from vascular dementia (VaD), and these differences may translate into differences in function. However, current evidence is mixed regarding how different dementia diagnoses affect activities of daily living (ADLs) and instrumental activities of daily living (IADLs). In one study, hospital utilization was higher for those with VaD compared with those with Alzheimer s dementia (AD) (1). Another study found no differences using the Disability Assessment for Dementia when comparing individuals with VaD and AD (2). A third study documented a higher prevalence of autonomic instability in patients with VaD comparable to Parkinson s and Lewy body dementia, suggesting that individuals with VaD may be at greater risk for falls as well as gait abnormalities relative to those with AD (3). Difficulties performing ADLs and IADLs among patients with VaD are often due to the neurological sequelae of a stroke. Depending on the location of the infarct/hemorrhage, a patient

COMPARING DISABILITY ACROSS DEMENTIA SUBTYPE 435 may have motor, language, visual, and/or postural functions affected. The risk of cognitive impairment after stroke increases with increasing age, stroke severity, and stroke recurrences among other risk factors (4). Furthermore, VaD patients likely have greater functional impairment due to the added impact of comorbid illnesses, such as heart failure, peripheral vascular disease, and complications of type 2 diabetes (2). In addition, executive function deficits are predictive of functional decline in patients with VaD (5 7). Although cognitive changes are dependent on the location of the ischemic event, deficits in executive function are common in patients with vascular cognitive impairment (8,9). In contrast, AD patients experience a progressive decline in their ability to independently perform ADL and IADLs as cognition deteriorates. IADLs are typically affected at earlier stages with worsening of memory and the development of behavioral disturbances, followed by a progressive decline in ADLs as executive function becomes more affected at later stages of the dementia (10 12). Thus, the psychometric differences that exist between VaD and AD patients may also explain differences in functional limitations. We hypothesized that a unique functional profile exists for individuals with VaD compared with those with AD. To test this hypothesis, we examined data from a nationally representative cohort of participants in the Aging, Demographics, and Memory Study (ADAMS) to determine the nature and severity of functional impairment among older adults with dementia due to different etiologies. Methods Sample The ADAMS sample comes from the larger Health and Retirement Study (HRS), an ongoing nationally representative cohort study of adults aged 51 years and older that was designed to investigate the health, social, and economic implications of aging in the United States. The HRS began in 1992, and the current HRS sample includes approximately 20,000 participants. The ADAMS is the first study of dementia in the United States that includes individuals from all regions of the country and which uses a single standardized diagnostic protocol in a community-based sample. The study began by recruiting a stratified random subsample of 1,770 individuals aged 70 years or older from five cognitive strata based on participants scores on the HRS cognitive tests (from either the 2000 or the 2002 wave). Full details of the ADAMS sampling design and selection procedures are described elsewhere (13). The ADAMS initial assessments occurred between July 2001 and December 2003, on average, 13.3 months after participants original HRS interview. Thus, participants were aged 71 years or older at the time of the initial assessment. A total of 856 individuals (56% of the nondeceased target sample) participated in all phases of the dementia assessment; additional details on participation rates are reported elsewhere (13). As part of that assessment, proxy informants (usually a spouse or an adult child) provided information about the participant s cognitive and functional decline, neuropsychiatric symptoms, and medical history. Informants also completed a questionnaire that included the short form of the Informant Questionnaire on Cognitive Decline in the Elderly and other questions regarding specific ADL and IADL limitations. A total of 744 informants completed and returned this questionnaire for a response rate of 86.9%. Of the ADAMS participants (n = 112, 13.1% of total sample) for whom questionnaires were not returned, 67 (59.8%) were nondemented, 30 (26.8%) had AD, 6 (5.4%) had VaD, and 9 (8.0%) had dementia due to other etiologies. There were no significant differences between participants for whom the questionnaire was and was not returned with respect to age, race, level of education, living arrangement, net worth, and gender. Variables and Their Measurement Measurements of disability. Functional limitations were assessed using a questionnaire completed by an informant that asked whether the participant had difficulty or required assistance in specific ADLs (bathing, dressing, eating, toileting, transfers, and walking) or IADLs (grocery shopping, preparing meals, taking medication, managing money, and making phone calls). Dementia assessment and diagnosis. Cognitive diagnoses were assigned in three general categories: normal cognitive function, cognitive impairment not demented (CIND), and dementia. The ADAMS in-person evaluation was a 3- to 4-hour structured assessment conducted in the participant s residence by a nurse and neuropsychology technician, both specially trained in data collection for dementia evaluation. The neuropsychology technician administered the neuropsychological test battery to the participant, and the nurse met separately with the informant to obtain detailed information about the participant, including a chronological history of cognition and function, medical and psychiatric history, family history of memory problems, current medications use, and current behavioral and psychiatric symptoms. A consensus panel of clinicians used available clinical data to assign the final diagnosis based on published criteria. Dementia diagnosis was based on the guidelines from the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; diagnoses of AD and other types of dementia were based on currently accepted clinical criteria (14). The National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l Enseignement en Neurosciences criteria as operationalized for research were used for VaD (15,16).

436 Gure et al. The definition of CIND and its subtypes was developed primarily on the basis of the accumulated clinical experience of a group of researchers common to ADAMS and three other epidemiological studies of dementia. CIND was defined as mild cognitive or functional impairment, reported by the participant or informant that did not meet the criteria for dementia, or performance on neuropsychological measures that was both below expectation and greater than or equal to 1.5 SD below published norms on any test. For the purposes of the current study, we used four subcategories for cognitive impairment: nondemented (normal and CIND), VaD, AD, and dementia due to other causes (Parkinson s disease, progressive supranuclear palsy, normal pressure hydrocephalus, frontal lobe dementia, severe head trauma, alcoholic dementia, amyotrophic lateral sclerosis with dementia, hypoperfusion dementia, and probable Lewy body dementia). The following other health conditions were identified based on self-report or informant report during the 2000 and 2002 core interview waves of the HRS: hypertension, osteoarthritis, lung disease, diabetes, heart problem, psychiatric problem, incontinence, falls, and cancer. Sociodemographic factors. Demographic variables included in the analysis were age, sex, race (non-hispanic white, non-hispanic black, and Hispanic), marital status, educational attainment, living arrangement, and net worth. These variables were obtained from the 2000 and 2002 HRS core interviews. The Clinical Dementia Rating (CDR) reflects an indirect evaluation of cognition and functional performance based on information obtained from both the informant and the participant during the course of the evaluation. Its 5-point scale characterizes six domains of cognitive and functional performance applicable to Alzheimer s disease and related dementias: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care (17). Its 5-point numeric scale quantifies the severity of dementia symptoms: 0 is normal, 0.5 is very mild, 1 is mild dementia, 2 is moderate, and 3 is severe. The total CDR staging score is calculated based on an algorithm developed at Washington University, St. Louis (18). Analysis. All analyses were conducted using STATA 10. Using ADAMS sampling weights, we computed the number of functional limitations by ADL and IADLs for the three dementia subtypes (AD, VaD, and dementia due to other etiologies) and for those who were nondemented (normal and CIND). Sample characteristics for the different groups were compared using chi-square and t tests, as appropriate, and were adjusted for the HRS complex sampling design. We used logistic regression to determine the independent association between dementia subtype and functional limitations. ADL limitations were dichotomized as 0 3 versus 4 6 to identify those with the greatest burden of ADL impairment. IADL burden also was dichotomized as 0 1 and 2 5. The first regression model controlled for sociodemographic characteristics, such as age, gender, and education. The second model further controlled for nonvascular comorbid conditions that might contribute to disability (lung disease, psychiatric problem, osteoarthritis, injury by fall, and urinary incontinence). The CDR total score was utilized as a categorical variable in the final logistic regression model, using four categories based on the distribution of scores in the sample. Results Sample Characteristics Overall, the sample represented a wide range of age levels, including a significant percentage of respondents who were aged 90 years and older. Table 1 shows the demographic and health characteristics of ADAMS participants for demented and nondemented subgroups. Respondents with AD were the oldest age group with a mean age of 86.1 years (p <.001). There were no significant differences among groups with respect to gender (p =.23) or race (p =.32). Those with AD and VaD had less education than nondemented respondents (p =.01). The average total CDR scores were significantly higher for the AD group compared with those with VaD, dementia due to other etiologies, and nondemented categories (p <.001 and p =.007, respectively). Those with dementia had higher rates of stroke (p <.001), diabetes (p =.009), lung disease (p =.009), heart problems (p <.001), and falls (p =.004) compared with respondents with normal cognition. There was no significant difference in the proportion of respondents with hypertension (p =.09), cancer (p =.66), a psychiatric problem (p =.29), arthritis (p =.09), or urinary incontinence (p =.23). Not surprisingly, stroke and heart problems were more often reported by respondents with VaD or their proxies compared with the other dementia subgroups (p.001). ADAMS participants with dementia due to other medical conditions were more likely to report diabetes (compared with AD, p =.008; compared with VaD p =.04). Functional Limitations As expected, those with dementia had significantly more ADL (Figure 1) and IADL limitations (Figure 2) than those without dementia. Within subgroups of dementia, however, those with VaD and dementia due to other etiologies had a greater number of ADL limitations compared with those with AD (both p <.001). Also, respondents with VaD had a higher mean number of IADL limitations compared with the other dementia subgroups (p <.001). Considering each ADL item separately (Figure 3), some ADL limitations, such as walking, bathing, and dressing did not differ significantly across dementia subtypes. Respondents with VaD and other etiologies for dementia, however, reported more difficulty with eating (p =.005), toileting,

COMPARING DISABILITY ACROSS DEMENTIA SUBTYPE 437 Table 1. ADAMS Sample Characteristics by Subgroup of Cognitive Impairment All AD VaD Other Nondemented p Value Overall 744 (100) 199 (100) 42 (100) 22 (100) 481 (100) Age, y (M ± SD) 81.6 ± 7.1 86.1 ± 6.7 83.8 ± 6.2 82.6 ± 7.1 79.5 ± 6.3 <.001 71 79 311 (59.3) 29 (12.5) 12 (25.1) 9 (59.2) 261 (65.3) 80 89 320 (33.8) 108 (64.4) 23 (59.9) 9 (36.2) 180 (29.5) 90 113 (7.0) 62 (23.1) 7 (15.0) 4 (4.6) 40 (5.0) CDR total, M ± SD 1.3 ± 6.6 2.3 ± 6.4 1.43 ± 1.1 1.8 ± 1.1 0.8 ± 7.1 <.001 Gender Male 313 (39.9) 52 (27.7) 18 (40.1) 12 (38.6) 231 (41.3).23 Female 431 (60.1) 147 (61.4) 24 (59.9) 10 (61.4) 250 (58.7) Education (y) <12 379 (34.1) 116 (48.8) 23 (45.6) 12 (58.7) 225 (31.6).01 12 177 (28.6) 48 (30.2) 10 (37.3) 4 (6.9) 115 (28.6) >12 188 (37.3) 35 (20.9) 9 (17.2) 3 (34.4) 141 (39.8) Net worth 5,500 180 (13.2) 71 (34.4) 17 (33.2) 6 (20.7) 86 (10.1) <.001 5,501 74,000 185 (20.2) 49 (25.3) 9 (33.3) 8 (35.4) 119 (19.0) 74,001 249,600 187 (29.3) 42 (17.0) 9 (19.8) 5 (0.4) 131 (30.8) 249,601 192 (37.3) 37 (23.3) 7 (13.8) 3 (6.9) 145 (40.1) Living arrangement Married 298 (46) 49 (25.1) 9 (16.3) 6 (16.1) 232 (49.8) <.001 Lives with someone 135 (11.8) 53 (24.4) 11 (15.5) 4 (6.4) 67 (10.4) Lives alone 311 (42.2) 22 (68.2) 22 (68.2) 10 (77.5) 182 (39.8) Race Non-Hispanic, white 544 (87.4) 143 (83.6) 32 (86.8) 15 (87.8) 354 (87.8).32 Non-Hispanic, black 122 (7.0) 38 (10.8) 7 (10.6) 5 (9.8) 72 (6.4) Hispanic 78 (5.6) 18 (5.6) 3 (2.5) 2 (2.4) 55 (5.8) Chronic illness Stroke 141 (14.2) 42 (23.0) 37 (93.9) 6 (34.6) 56 (10.6) <.001 Hypertension 426 (60.2) 99 (50.6) 30 (76.0) 15 (61.2) 282 (60.9).09 Diabetes 143 (20.5) 18 (10.2) 9 (15.5) 10 (51.4) 106 (21.1).009 Lung disease 76 (9.3) 12 (6.9) 6 (24.5) 2 (11.4) 56 (9.1).009 Heart problem 250 (30.2) 67 (38.2) 15 (42.3) 10 (36.2) 158 (28.9) <.001 Psychiatric problem 156 (18.3) 57 (29.3) 11 (20.0) 7 (31.9) 81 (16.7).29 Cancer 136 (18.7) 37 (21.1) 9 (15.8) 3 (9.5) 87 (18.7).66 Arthritis 527 (71.8) 136 (68.4) 35 (88.8) 15 (84.1) 341 (71.5).09 Incontinence 221 (27.8) 77 (33.5) 14 (40.3) 10 (49.5) 120 (26.4).23 Falls 309 (36.4) 99 (47.3) 26 (55.1) 13 (47.2) 171 (34.5).004 Note: Values in parentheses are weighted column percentages derived using the ADAMS sampling weights. AD = Alzheimer s dementia; VaD = vascular dementia; Other = dementia due to other medical etiologies. and transferring compared with those with dementia due to AD. In reviewing each IADL item separately (data not shown), participants with VaD more often needed assistance with cooking and grocery shopping compared with those with AD (p <.05). Difficulty with using the telephone, managing medications, and money were consistently high across the dementia subtypes. Adjusted Association Between Dementia Subtype and Functional Limitations Table 2 shows the logistic regression models for the relationship of ADL limitations to dementia subtype. With full adjustment (Model 3), those with VaD had a greater odds (odds ratio [OR] 5.74; 95% confidence interval 2.60 12.69) of reporting greater than or equal to four ADL limitations compared with the AD group. Those with dementia due to other etiologies had significantly greater odds of possessing greater than or equal to four ADL limitations when compared with the AD group in both Models 2 and 3. Table 3 shows the logistic regression models result for IADL disability by dementia subtype. Although there was a trend toward higher odds of greater than or equal to two IADL limitations among those with VaD compared with those with AD, the OR did not reach statistical significance in any of the models. Discussion Using a large nationally representative sample of older adults with dementia due to a range of etiologies, we found that compared with individuals with dementia due to AD, those with VaD or due to other etiologies of dementia had more ADL limitations. After adjustment for participants sociodemographic characteristics, comorbid chronic medical conditions, and dementia severity, respondents with VaD and those with dementia due to other etiologies had greater odds of greater than or equal to four ADL limitations when compared with the AD group.

438 Gure et al. Figure 1. Mean number of activity of daily living (ADL) limitations by dementia subtype. *p <.001 for comparison of mean number of ADL limitations across dementia subtype. In addition to the progressive loss of cognitive skills, a core feature of dementia is a decline in the ability to perform tasks needed to maintain independent living. As found in other studies, those with AD had fewer chronic conditions than those with VaD or dementia due to other etiologies (1,19,20). The prevalence of ADL impairments among AD- AMS participants fits the well-described hierarchical pattern of disability in ADLs among older adults. An older adult s disability pattern is usually characterized by lower extremity disability preceding upper extremity disability. Walking is the most common disability in older adults, which is followed by bathing, dressing, transferring, toileting, and feeding (21). This pattern is influenced by physical flexibility/dexterity as well as cognitive function (22). The finding of lower ADL burden in AD patients is consistent with the well-described natural history of AD, which entails Figure 2. Mean number of instrumental activities of daily living (IADLs) by dementia subtype. *p <.001 for comparison of mean number of IADL limitations across dementia subtype.

COMPARING DISABILITY ACROSS DEMENTIA SUBTYPE 439 Figure 3. Prevalence of limitations in activity of daily living (ADLs) by dementia subtype. *p <.05 for comparison of prevalence of ADL limitations across dementia subtype. progressive IADL limitations occurring during the earlier stages of the disease, followed by progressive loss of ADL limitations in the later stages (10,23). We expected to find that AD participants would have more significant limitations in IADL than other participants with non-ad dementias, particularly because AD participants had higher dementia severity than those with VaD and dementia due to other etiologies. In fact, the AD group had a lower mean number of IADL limitations compared with those with VaD, although there was no statistically significant association between IADL limitations and dementia subtype in the adjusted multivariate model. One potential hypothesis to explain this finding is that the IADLs that were reported by informants as most difficult for those with VaD (cooking and shopping) are more likely due to residual motor deficits than cognitive deficits. VaD as a disease entity is a heterogeneous mix of conditions related to cerebrovascular disease that can manifest in processes such as a single, localized infarcted region, hypoperfusion syndromes, or hemorrhage (15). VaD may have a stepwise course, stabilization, or partial recovery of cognitive function (9); our cross-sectional analysis is unable to account for the heterogeneity that might exist in this VaD population, and therefore, our findings do not fully characterize functional performance among those with VaD beyond a fixed point in time. Individuals with dementia due to other etiologies had the highest degree of ADL limitations. However, this group of respondents was highly heterogeneous, composed of individuals with numerous dementia diagnoses, such as Parkinson s disease, Lewy body dementia, and normal pressure hydrocephalus. Although each of the dementia diagnoses in Table 2. The Association of Dementia Subtype With Greater Than or Equal to Four Activity of Daily Living Limitations Odds Ratio (95% Confidence Interval) Dementia Subgroup Model 1 Model 2 Model 3 Alzheimer s Reference Reference Reference dementia Vascular 1.73 (0.71 4.26) 2.32 (0.64 8.40) 5.74 (2.60 12.69) Other etiologies 3.50 (0.76 15.77) 8.47 (2.61 27.48) 21.23 (7.25 62.16) Nondemented 0.16 (0.09 0.27) 0.23 (0.13 0.41) 0.91 (0.34 2.48) Note: Model 1: unadjusted; Model 2: includes sociodemographic variables race, gender, education level, and age; Model 3: includes Model 2 + nonvascular chronic conditions + Clinical Dementia Rating Scale. Table 3. The Association of Dementia Subtype With Greater Than or Equal to Two Instrumental Activity of Daily Living Limitations Odds Ratio (95% Confidence Interval) Dementia Subgroup Model 1 Model 2 Model 3 Alzheimer s Reference Reference Reference dementia Vascular 2.33 (0.60 8.98) 3.55 (0.81 15.59) 4.90 (0.82 29.31) Other etiologies 0.81 (0.12 5.59) 1.65 (0.24 11.14) 1.32 (0.25 6.84) Nondemented 0.05 (0.03 0.09) 0.09 (0.04 0.16) 0.39 (0.18 0.83) Note: Model 1: unadjusted; Model 2: includes sociodemographic variables race, gender, education level, and age; Model 3: includes Model 2 + nonvascular chronic conditions + Clinical Dementia Rating Scale.

440 Gure et al. this category is typically associated with high levels of ADL and IADL functional impairment (24 27), we are unable to draw firm conclusions about functional impairment within each dementia diagnosis that falls under this category. Comparative studies of functional impairment across subtypes of dementia are few. Our study has several strengths: a population-based sample of a relatively large number of participants with cognitive impairment, CIND, and dementia, a comprehensive assessment and diagnostic protocol to classify respondents cognitive status, and the use of informants to gain more reliable data about functional impairment. Nevertheless, there are limitations that warrant comment. The ADAMS participation rate (56%) was lower than hoped for but comparable to other population studies of this age group, such as the Cardiovascular Health Study (participation rate of 57.3%) (28) and the Canadian Study of Health and Aging (68.5%) (29). Nonparticipation could result in selection bias. Nonresponse bias was addressed by the ADAMS by use of archived information from prior interviews. Available measures were used to create response propensity models to adjust for factors that could contribute to significant selection bias (30). There was also a lack of neuroimaging and other medical tests for all participants, which may have influenced the accuracy with which non-ad dementias were identified. We relied on informant-based assessments of functional impairment rather than performance-based evaluations; this may have resulted in some inaccuracy in functional assessment. This study suggests that individuals with different subtypes of dementia have unique needs when it comes to their ADL limitations. Individuals with VaD or due to other etiologies of dementia had more ADL limitations than those with AD. After full adjustment of the model, individuals with VaD had greater odds of greater than or equal to four ADL limitations when compared with the AD group. These findings have implications for the type of community-based services most likely to be required by individuals with dementia and their caregivers. Out-of-home day care services which provide lower intensity services like socialization and general purpose programs (eg, exercise, meals) generally serve dementia clients with fewer ADL impairments than those services provided in-home (31). Because older adults with non-ad dementia have higher levels of ADL impairment, the model of adult day health care, with additional services of nursing, occupational, and physical therapy, is likely to be more appropriate. Yet, only 42% of adult day care centers nationally have a medical component. 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