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Prevalence of Parkinson Disease and Parkinson Disease Dementia in Community Nursing Homes
Prevalence of Parkinson Disease and Parkinson Disease Dementia in Community Nursing Homes Matthew Hoegh, M.D., Aalamgeer K. Ibrahim, M.D., John Chibnall, Ph.D., Beenish Zaidi, M.D., George T. Grossberg, M.D.
Objective: To estimate the prevalence of Parkinson disease (PD) and Parkinson disease dementia (PDD) in community nursing homes. To estimate how many residents who meet criteria for PDD have been diagnosed with PDD and prescribed a Federal Drug Administration (FDA)-approved treatment for PDD. Setting: Three private Saint Louis metropolitan area nursing homes. Participants: Fifty-five residents with a chart diagnosis of PD from a total of 714 residents were identified. Sixteen subjects or families did not give consent and two were excluded from the study because advanced stage of the illness impaired evaluation. Thirty-seven subjects with an established diagnosis of PD participated in the study. Design and Measurements: A chart review was used to identify the study sample: residents with an established diagnosis of PD. Consent was obtained from the nursing home administration, families or guardians, and the residents themselves (where applicable). Study data were obtained from review of residents’ medical charts, family/ caregiver interview, resident interview, resident cognitive testing (Mini-Mental State Examination, clock drawing test), and resident depression assessment (15-item Geriatric Depression Scale). Diagnosis of PDD was defined using existing literature and described below. Data were analyzed using SPSS version 15. Result: Of the 714 nursing home residents, 55 (7.7%) met criteria for PD. Of these, 37 participated in the study and 18 (48.6%) met criteria for PDD. None were diagnosed with PDD in the charts and 11.1% (2 of 18) were on FDA-approved treatment. Conclusion: In this sample of nursing home residents, the prevalence of PD was 7.7% and the overall prevalence of PDD was 3.7%. PDD remains an unrecognized entity in the nursing home setting. Close to half (48.65%) of nursing home residents with PD may have PDD at any given time and they remain undiagnosed and largely undertreated. (Am J Geriatr Psychiatry 2013; 21:529e535) Key Words: Cognition disorders, dementia, dementia/etiology, geriatric psychiatry, long-term care facilities, nursing home, Parkinson disease, Parkinson disease/complications, Parkinson disease dementia, Parkinson disease dementia/prevalence
Received April 13, 2011; revised September 14, 2011; accepted November 20, 2011. From the Saint Louis University School of Medicine, Saint Louis, Missouri. Send correspondence and reprint requests to Matthew Hoegh, M.D., Saint Louis University School of Medicine, 5220 Miami St. Saint Louis, MO 63139. e-mail: [email protected] Ó 2013 American Association for Geriatric Psychiatry http://dx.doi.org/10.1016/j.jagp.2012.12.007
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Prevalence of PD and PDD in Community Nursing Homes
P
arkinson disease dementia (PDD) is being discussed more frequently in the medical literature. It is distinct from other forms of dementia in that it occurs in the setting of established Parkinson disease (PD), with onset of cognitive decline occurring at least 2 years after the onset of PD. It is estimated that approximately 30%e50%1e4 of patients with PD will eventually develop PDD, with a mean onset of 8e10 years from the diagnosis of PD.5 PDD accounts for approximately 3%e4% of all dementias.3 PD has a mean age of onset of 60 years and many patients with this illness have significant functional impairment requiring them to reside in nursing homes. No studies have established the prevalence of PDD in community nursing homes. In addition, it is hypothesized that most patients with PDD are undiagnosed or are misdiagnosed as having other forms of dementia. Thus, it is also hypothesized that most patients with PDD are not on Federal Drug Administration (FDA)-approved treatment for PDD. The goal of this study was to determine the prevalence of PDD in community nursing home residents and to assess how many residents who met criteria for PDD were actually diagnosed with PDD and prescribed an FDAapproved treatment for PDD.
METHODS Approval for the study was obtained from the institutional review board of Saint Louis University School of Medicine to conduct the study at three community nursing homes in the Saint Louis metropolitan area. In total, the facilities had a combined resident population of 714. Written informed consent was obtained from families, guardians, or the nursing home residents themselves (where applicable). Agreement to allow the study to be conducted was obtained from the administrators of the relevant facilities, who in turn obtained approval from their corporate headquarters. Residents with a medical chart diagnosis of PD were selected for further assessment. A thorough chart review then followed. Medications and relevant past medical history were recorded. A record was made of the diagnosis of other dementias in the chart. Participants with a history of dementia were grouped into two categories: Alzheimer dementia and other
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dementias (which included the categories of Lewy body, vascular dementia, and dementia not otherwise specified). History of depression, treatment for depression, and history of any mood disorders were noted. A careful history of the onset of PD and progression of the disease was obtained from the family, caregiver, and resident (where applicable), with particular attention to the onset of cognitive decline in relation to PD. These interviews, as well as the chart review, were used to clearly establish whether a subject’s onset of cognitive decline occurred at least 2 years after a diagnosis of PD. Residents were assessed for orientation, attention and concentration, memory, executive functioning, and visuospatial perception, which are parameters of impairment often present in PDD.6,7 Several of these parameters were assessed using the Mini-Mental State Examination (MMSE). Executive functioning was assessed using the clock drawing test. Residents were also assessed for depression using the abbreviated version of the Geriatric Depression Scale comprising 15 questions (GDS-15). Any resident who had a GDS-15 score of 7 or more was considered depressed and thus could not be assessed for PDD. The original criteria use a cutoff of 4 on the GDS as exclusion. This may give a high false-positive rate of depression and exclude people from the final sample. On the basis of clinical experience and literature reviews, a cutoff score of 7 was used as it had a good trade-off between sensitivity and specificity for the GDS. Anyone with an MMSE score of less than 26 was considered to have dementia and cognitive impairment. Any participant losing a point on the clock drawing test was thought of as having executive impairment. Attention and concentration were assessed using “serial sevens” or spelling “world” backwards, with two or more mistakes scored as positive for impaired attention and concentration. Failure to properly draw the intersecting pentagons on the MMSE was scored as positive for impaired visuospatial perception. Finally, one or more errors on three word recall defined memory impairment. Criteria and parameters for evaluation were adapted from the existing literature.4,8,9 PDD was diagnosed using the criteria shown in Figure 1. Data were analyzed using SPSS version 15. Descriptive statistics were computed regarding PD, PDD, and FDA-approved treatments for PDD.
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FIGURE 1. Parkinson’s disease dementia criteria.
RESULTS The sample consisted of 714 residents, nearly evenly distributed between three nursing homes in the Saint Louis metropolitan area. Of these, 55 residents had a chart diagnosis of PD. Thus, the prevalence of PD in these nursing homes was 7.7% (95% confidence interval [95% CI]: 6.0e9.9). Of the 55 residents with a diagnosis of PD, 37 (67.3%) participated in the study. Sixteen subjects were excluded from the sample because consent was not available either because the guardian was unreachable or more commonly the patient/family refused to consent to the study. Two participants were excluded because they were in an advanced stage of the illness and in an almost comatose condition. An assessment of their cognitive function was not possible. However, on the basis of the history given by the family or caregivers of these two participants, it is suspected that they were likely to have PDD. Table 1 shows the distribution of PD diagnoses for each nursing home evaluated. The study sample consisted of 37 residents. Residents were between the ages of 61 and 99 years with a mean age of 82.3 years. Twenty-three (62.2%) were women and 14 (37.8%) were men. Table 2 displays summary information for the cognitive and depression assessments. MMSE scores ranged from 9 to 30
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with a mean of 20.5 (SD ¼ 7.3). Thirty residents (81.1%) had impairments in memory, 24 (64.9%) had impairments in visuospatial construction, and 30 (81.1%) had impairments in executive function. GDS scores varied from 0 to 12 with a mean of 4.1 (SD ¼ 3.2). Twentynine (78.4%) participants had a GDS of less than 7, and 8 (21.6%) had GDS scores of 7 or more. On the same note, 23 (62.2%) participants had a chart history of depression and 2 had other mood disorders. Eight participants had a diagnosis of Alzheimer dementia and 17 had a diagnosis of other dementias. Within the total study sample, 29 (78.4%) participants were on anti-parkinsonian medications, 28 (75.7%) were on antidepressants, 12 (32.4%) were on medications for dementia other then rivastigmine, 4 (10.8%) were on rivastigmine, and 5 (13.5%) were on antipsychotics. A total of 18 of the 37 residents 48%; (95% CI: 33.5e64.1) with PD met criteria for PDD; however, 2 had a GDS score greater than 7 and were excluded from the diagnosis of PDD. Twenty of the 37 residents had onset of cognitive decline 2 years or more after onset of PD. The PDD group consisted of 10 (55.6%) women and 8 (44.4%) men. Among the residents who met criteria for PDD, 94.4% had impairments in executive functions and memory and 72.2% had impairments in visuospatial perception. Of the 18 subjects with PDD, 7 (38.9%) had a diagnosis of Alzheimer disease and another 7 (38.9%) had other dementias diagnosed in the chart. There were no residents who met criteria for PDD with a previous diagnosis of PDD. A full comparison of chart dementia diagnoses between the study group that fit criteria for PDD and the total study sample is seen in Table 3. Nine subjects with PDD had history of depression. As shown in Table 4, 13 (72.2%) subjects with PDD were on antidepressants, 16 (88.9%) were on antiparkinsonian medications, 7 (38.9%) were on anti dementia drugs other than rivastigmine, and 2 (11.1%) were on rivastigmine. Extrapolating the 48.6% prevalence of PDD to the 18 residents with PD who did not participate, the prevalence of PDD was estimated at 3.7% (95% CI: 2.6e5.5).
DISCUSSION PDD is a distinct form of dementia that occurs in the context of established PD. The prevalence of PDD
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Prevalence of PD and PDD in Community Nursing Homes
TABLE 1. PD Prevalence and Study Participation Across Nursing Homes Site 1 Total residents Residents with PD Nonparticipating PD residents Evaluable PD residents
243 18 3 15
(34%) (32.7%) (16.7%) (40.5%)
Site 2 212 20 8 12
(29.7%) (36.4%) (44.4%) (32.4%)
Site 3 259 17 7 10
Total
(36.3%) (30.9%) (38.9%) (27%)
714 55 18 37
TABLE 2. Cognitive Impairment and Depression in PD Group (N [ 37)
TABLE 4. Medications in Subjects Who Met Criteria for PDD (n [ 18)
Test
Medication
No. of Residents
Dementia (MMSE <26) Attention and concentration impairment (2 errors on Serial 70 s or Backwards WORLD) Executive impairment (1 error on clock drawing test) Visuospatial impairment (any error on intersecting pentagons) Memory impairment (1 error on the three word Recall) Depression (GDS-15 7)
26 (70.3%) 20 (54.1%) 30 (81.1%) 24 (64.9%) 30 (81.1%) 8 (21.6%)
TABLE 3. Chart Dementia Diagnoses in the PDD Group (n [ 18) versus Total PD Group (n [ 37) Chart Diagnosis Alzheimer disease Other dementia No diagnosis PDD
No. of Residents With PDD 7 7 4 0
(38.9%) (38.9%) (22.2%) (0%)
No. of Total residents 8 17 12 0
(21.6%) (45.9%) (32.4%) (0%)
was as high as 3.75% in this nursing home sample. No prior study has established the prevalence of PDD in nursing homes, thus there are no estimates for comparison. Of the subjects with PD, 48.65% met criteria for PDD, which is consistent with earlier estimates in the literature that range from 30% to 50%. The fact that this number is toward the higher end of the range (close to 50%) is likely because we sampled residents in nursing homes who would be expected to have a higher prevalence compared with the general population, given their advanced age and the level of care required in those who enter a nursing home (who tend to have more advanced PD upon admission). These risk factors, older age, duration of PD, and severity of parkinsonism, have been shown to impact the incidence of PDD.10e14 The design of this study relied on an existing chart diagnosis of PD. All chart diagnoses were documented using appropriate diagnostic criteria in a clinical setting by a board-certified primary care physician. These diagnoses were used as inclusion
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Rivastigmine Anti-PD Antidepressants Antidementia
No. of Residents 2 16 13 7
(11.1%) (88.9%) (72.2%) (38.9%)
criteria for the sake of our study and are understood as a limitation. Using an already established diagnosis may have missed residents with undiagnosed PD. At the same time, the charts reviewed were nursing home charts and though they contained clinical notes from the patient’s primary providers, they by no means are as reliable as a medical chart. We did not seek out a medical chart as it was outside what was permitted by the institutional review board. The nursing home charts were updated after every visit of the provider but there is likelihood of error in updating. This could affect the accuracy of the prevalence estimates. PD is a clinical diagnosis and there is the possibility of other Parkinson syndromes being labeled as PD. Our study was limited by the fact that we did not attempt to ascertain whether we were dealing with PD or one of the Parkinson syndromes. Reviewing the medical chart could reduce some of this error. This may be an interesting area for future research. The design of our study also established a “2-year rule,” where a clear timeline of PD diagnosis at least 2 years prior to development of cognitive decline must be present. This was used to ensure that cognitive decline described in subjects was confidently within the context of established PD. Although appropriate to establish criteria for the sake of our study, this rule can be considered an arbitrary distinction. The specific length of time that parkinsonism actually precedes cognitive decline has been shown to not correlate with pathological differences in patients.15 The final study sample consisted of 37 participants out of a total of 55 who were found to have PD. We excluded two participants from the study because
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Hoegh et al. they were in a comatose state and could not have participated in our clinical exam. Had they been included and met criteria for PDD the prevalence estimate would have gone up to 54%, this is likely based on caregiver history. In addition, it would be interesting to know how the 16 residents with PD who were excluded from the study because of failure to obtain consent would have affected the prevalence estimates, given that we do not know their clinical status. It is likely that they would have same rate of PDD, but there could be a selection bias. One could argue that the residents who refused consent may have had PD for a long time and so had advanced stage of the illness at which point they would not have seen the need to participate. This means that we could see a higher incidence of PDD and thus could have resulted in a higher prevalence than what we estimated. It could also be argued that the residents who refused consent had little or no cognitive decline at which point they would not have seen the need to participate. This would yield a lower incidence and could have resulted in a lower prevalence than what we estimated. The final study sample consisted of a total of 37 participants. Of these, 23 (62.2%) were women and 14 (37.8%) were men. National nursing home demographics estimate a total female distribution of 71.1%.16 Our study sample is consistent with this trend in gender distribution and thus allows for greater confidence when generalizing data from this study to the nursing home population as a whole. More importantly, gender alone is not considered a risk factor for PDD, whereas women with PD have been found to have a greater life expectancy, they have not been found to be a greater risk for PDD.17,18 Thus an unequal gender distribution would not alter the results of our study. The methods employed in our study also had some drawbacks. Major depression is an exclusion criterion for PDD. We estimated major depression using GDS15 with 7 as a cutoff for a major depressive episode. This is by no means a replacement for a clinical interview but GDS has proven to be an effective tool for depression in the geriatric population including people with PD.19 According to the original criteria, a score cutoff of 4 was used for exclusion due to depression. Although this has a high sensitivity, the specificity was low. On the basis of other studies, we employed a score cutoff of 7 on the GDS, which was
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an even trade-off between a slightly lower sensitivity and a higher specificity.20 We employed the clock drawing as a measure of executive dysfunction, yet we did not assess for decline in other areas of executive dysfunction such as lexical fluency. For assessing visuospatial orientation, we relied on the intersecting pentagon test. People with PD have some level of motor deficits and so it is hard to determine whether failure to draw the intersecting pentagon was visuospatial or motor in origin. Compared with the non-PDD group (51.6%), the PDD group had a higher percentage of residents with impairment in all four areas of tested cognitive functioning. Executive and memory impairment were more commonly affected among the PDD group as compared with the non-PDD group. History of depression was also more common in the non-PDD subgroup (73.7%) as opposed to PDD subgroup (50%). No participant in this study had a chart diagnosis of PDD. This, we believe, was because of a relative lack of awareness among primary care providers about PDD as a distinct entity, as well as a lack of awareness of the clinical implications of PDD. This finding is of significant clinical value because when the total absence of a PDD diagnosis in the chart is compared with the prevalence data found in our study, a large discrepancy is seen. This discrepancy establishes a need to educate and create awareness among primary care providers about PDD. Though we did not take into account who made the diagnosis of PD, a primary care provider or a neurologist, it certainly would be an interesting fact to know to assess whether there are any differences between the two groups in diagnosing PD and dementia syndromes. There were 8 (21.6%) participants with a diagnosis of Alzheimer disease and 17 (45.9%) participants with a diagnosis of other dementias (Lewy body, vascular dementia, and dementia not otherwise specified). The results showed a significant overlap among participants with a diagnosis of Alzheimer disease and those who met criteria for PDD. Seven of the eight participants with a chart diagnosis of Alzheimer disease met the criteria for PDD. This could be because of a high comorbidity of PD with Alzheimer disease or incorrect diagnosis of Alzheimer disease. The parameters for diagnosis of PDD used in this study included evaluations that separate Alzheimer disease and PDD on the basis of their cognitive impairment profiles. Past analyses comparing
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Prevalence of PD and PDD in Community Nursing Homes the profiles of cognitive impairment of AD or PDD have suggested that a diagnosis could be predicted from the cognitive profile alone with 74.7% accuracy.7 However, there were no significant differences in the cognitive profiles of our PDD group and the non-PDD group with dementia syndromes. This supports many previous studies that although there are differences in the cognitive profiles of individuals with PDD and AD, these are more apparent in early stages and thus making the distinction clinically can be challenging.7 Our sample ranged from mild cognitive impairment to severe and so could explain why we did not see any patterns in the decline in various cognitive domains between the PDD and AD groups. Although incorrect diagnosis could be a reason for the overlap seen, this distinction is not simple and the possibility of this comorbidity does limit our study. On the contrary, to the high overlap seen with Alzheimer disease, participants with a previous diagnosis of other dementias were fairly evenly distributed between the PDD(38.9%) and nonPDD (52.6%) subgroups. We did not account for and rule out other dementia syndromes such as vascular dementia and this is another limitation of our study. However, the prevalence of pure vascular dementia syndromes is fairly low and so we believe that it may not affect the results significantly. One can highlight the clinical implications and relevance of diagnosing PDD. Rivastigmine is a cholinesterase inhibitor and the only FDA-approved treatment for PDD with statistically significant treatment benefits.21,22 This would make it useful to differentiate PDD from other forms of dementias so as to guide the selection of the appropriate therapeutic agent. Because of its FDA-approved status, rivastigmine specifically was separated in our study from other cholinesterase inhibitors in an effort to distinguish treatment for PDD from general use of a cholinergic agent for other cognitive impairment. Among our subjects, 12 were on cholinesterase inhibitor medications other than rivastigmine (such as
donepezil) whereas 4 were on rivastigmine. Of the 18 subjects who met criteria for PDD, only 2 were on rivastigmine. It is possible that in these cases the clinician may have suspected the possibility of PDD or may just have been using rivastigmine as a cholinergic agent for cognitive impairment. There is also the possibility that some of these participants had been tried on rivastigmine and were unable to tolerate it and such were placed on another cholinesterase inhibitor as appropriate treatment for their suspected PDD. Also, rivastigmine has not specifically been shown in the literature as clearly superior to other cholinesterase inhibiting agents, there is the possibility of physician preference for another cholinesterase inhibitor. Because of these possibilities it is not possible to extrapolate that all 16 subjects who met criteria for PDD and were not on rivastigmine were being treated inappropriately. PDD remains unrecognized as a distinct entity and there is a high likelihood that it is diagnosed as another dementia syndrome. This may interfere in the choice of the most appropriate treatment agent.
CONCLUSION PDD is a distinct form of dementia in the presence of established PD. It can complicate the disease course in nearly half (48.65%) of the residents with PD. It has a prevalence of up to 3.7% among residents in the nursing homes represented in this research. It remains an unrecognized entity among primary care providers as shown by our study. In addition, PDD is largely treated as other types of dementia. It is important to be mindful of this entity and to educate and create awareness among primary care providers about PDD. Dr. Grossberg serves as a consultant to Novartis Pharmaceuticals and his institution has received research funding from Novartis.
References 1. Cummings JL: Intellectual impairment in Parkinson’s disease: clinical, pathologic, and biochemical correlates. Geriatr Psychiatry Neurol 1988; 1:24e36 2. Aarsland D, Zaccai J, Brayne C: A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord 2005; 20: 1255e1263
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3. deLau LM, Schipper CM, Hofman A, et al: Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study. Arch Neurol 2005; 62:1265e1269 4. Goetz CG, Emre M, Dubois B: Parkinson’s Disease dementia: definitions, guidelines, and research perspectives in diagnosis. Ann Neurol 2008; 64(suppl 2):S81eS92
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Hoegh et al. 5. Aarsland D, Andersen K, Larsen JP, et al: Prevalence and characteristics of dementia in Parkinson disease: an 8 year prospective study. Arch Neurol 2003; 60:387e392 6. Noe E, Marder K, Bell KL, et al: Comparison of dementia with Lewey bodies to Alzheimer’s disease and Parkinson’s disease with dementia. Mov Disord 2004; 19:60 7. Bronnicl K, Emre M, Lane R, et al: Profile of cognitive impairment in dementia associated with Parkinson’s disease compared with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2007; 78(10): 1064e1068 8. Aarsland D, Bronnick K, Ehrt U, et al: Neuropsychiatric symptoms in patients with Parkinson’s disease and dementia: frequency, profile and associated care giver stress. J Neurol Neurosurg Psychiatry 2007; 78:36 9. Poewe W, Gauthier S, Aarsland D, et al: Diagnosis and management of Parkinson’s disease dementia. Int J Clin Pract 2008; 62(10):1581e1587 10. Mayeux R, Denaro J, Hemenegilo N, et al: A population-based investigation of Parkinson’s disease with and without dementia. Relationship to age and gender. Arch Neurol 1992; 49:492 11. Hobson P, Meara J: Risk and incidence of dementia in cohort of older subjects with Parkinson’s disease in the United Kingdom. Mov Disord 2004; 19:1043 12. Aarsland D, Andersen K, Larsen JP, et al: Risk of dementia in Parkinson’s disease: a community-based, prospective study. Neurology 2001; 56:730 13. Reid WG, Hely MA, Morris JG, et al: Dementia in Parkinson’s disease: a 20 year neuropsycological study (Sydney
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14.
15. 16. 17. 18.
19.
20.
21. 22.
Multicentre Study). J Neurol Neurosurg Psychiatry 2011; 82(9): 1033e1037 Levy G, Schupf N, Tang MX, et al: Combined effect of age and severity on the risk of dementia in Parkinson’s disease. Ann Neurol 2002; 51:722 McKeith I, Mintzer J, Visse M, et al: Dementia with Lewy bodies. Lancet Neurol 2004; 3:19 CDC/National Center for Health Statistics: Nursing Home Current Residents Tables, 2008. www.cdc.gov. Accessed March 23, 2011. Aarsland D, Kurz MW: The epidemiology of dementia associated with Parkinson’s disease. Brain Pathol 2010; 20(3):633e639 Buter TC, van den Hout A, Matthew FE, et al: Dementia and survival in Parkinson disease: a 12 year population study. Neurology 2008; 70(13):1017e1022 Tumas V, Rodriques GC, Farias TL, et al: The accuracy of diagnosis of major depression in patients with Parkinson’s disease: a comparative study among the UPDRS, the geriatric depression scale and the Beck depression inventory. Arq Neuropsiiquiatr 2008; 66(2A):152e156 Almeida OP, Almeida SA: Short versions of the geriatric depression scale: a study of their validity for diagnosis of a major depressive episode according to ICD-10 and DSM-IV. Int J Geriatr Psychiatry 1999; 14(10):858e865 Emre M, Aarsland D, Albanese A, et al: Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med 2004; 351:2509 Maidment I, Fox C, Boustani M: Cholinesterase inhibitors for Parkinson’s disease dementia. Cochrane Database Syst Rev 2006; (1):CD004747
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Objective: To estimate the prevalence of Parkinson disease (PD) and Parkinson disease dementia (PDD) in community nursing homes. To estimate how many residents who meet criteria for PDD have been diagnosed with PDD and prescribed a Federal Drug Administration (FDA)-approved treatment for PDD. Setting: Three private Saint Louis metropolitan area nursing homes. Participants: Fifty-five residents with a chart diagnosis of PD from a total of 714 residents were identified. Sixteen subjects or families did not give consent and two were excluded from the study because advanced stage of the illness impaired evaluation. Thirty-seven subjects with an established diagnosis of PD participated in the study. Design and Measurements: A chart review was used to identify the study sample: residents with an established diagnosis of PD. Consent was obtained from the nursing home administration, families or guardians, and the residents themselves (where applicable). Study data were obtained from review of residents’ medical charts, family/ caregiver interview, resident interview, resident cognitive testing (Mini-Mental State Examination, clock drawing test), and resident depression assessment (15-item Geriatric Depression Scale). Diagnosis of PDD was defined using existing literature and described below. Data were analyzed using SPSS version 15. Result: Of the 714 nursing home residents, 55 (7.7%) met criteria for PD. Of these, 37 participated in the study and 18 (48.6%) met criteria for PDD. None were diagnosed with PDD in the charts and 11.1% (2 of 18) were on FDA-approved treatment. Conclusion: In this sample of nursing home residents, the prevalence of PD was 7.7% and the overall prevalence of PDD was 3.7%. PDD remains an unrecognized entity in the nursing home setting. Close to half (48.65%) of nursing home residents with PD may have PDD at any given time and they remain undiagnosed and largely undertreated. (Am J Geriatr Psychiatry 2013; 21:529e535) Key Words: Cognition disorders, dementia, dementia/etiology, geriatric psychiatry, long-term care facilities, nursing home, Parkinson disease, Parkinson disease/complications, Parkinson disease dementia, Parkinson disease dementia/prevalence
Received April 13, 2011; revised September 14, 2011; accepted November 20, 2011. From the Saint Louis University School of Medicine, Saint Louis, Missouri. Send correspondence and reprint requests to Matthew Hoegh, M.D., Saint Louis University School of Medicine, 5220 Miami St. Saint Louis, MO 63139. e-mail: [email protected] Ó 2013 American Association for Geriatric Psychiatry http://dx.doi.org/10.1016/j.jagp.2012.12.007
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Prevalence of PD and PDD in Community Nursing Homes
P
arkinson disease dementia (PDD) is being discussed more frequently in the medical literature. It is distinct from other forms of dementia in that it occurs in the setting of established Parkinson disease (PD), with onset of cognitive decline occurring at least 2 years after the onset of PD. It is estimated that approximately 30%e50%1e4 of patients with PD will eventually develop PDD, with a mean onset of 8e10 years from the diagnosis of PD.5 PDD accounts for approximately 3%e4% of all dementias.3 PD has a mean age of onset of 60 years and many patients with this illness have significant functional impairment requiring them to reside in nursing homes. No studies have established the prevalence of PDD in community nursing homes. In addition, it is hypothesized that most patients with PDD are undiagnosed or are misdiagnosed as having other forms of dementia. Thus, it is also hypothesized that most patients with PDD are not on Federal Drug Administration (FDA)-approved treatment for PDD. The goal of this study was to determine the prevalence of PDD in community nursing home residents and to assess how many residents who met criteria for PDD were actually diagnosed with PDD and prescribed an FDAapproved treatment for PDD.
METHODS Approval for the study was obtained from the institutional review board of Saint Louis University School of Medicine to conduct the study at three community nursing homes in the Saint Louis metropolitan area. In total, the facilities had a combined resident population of 714. Written informed consent was obtained from families, guardians, or the nursing home residents themselves (where applicable). Agreement to allow the study to be conducted was obtained from the administrators of the relevant facilities, who in turn obtained approval from their corporate headquarters. Residents with a medical chart diagnosis of PD were selected for further assessment. A thorough chart review then followed. Medications and relevant past medical history were recorded. A record was made of the diagnosis of other dementias in the chart. Participants with a history of dementia were grouped into two categories: Alzheimer dementia and other
530
dementias (which included the categories of Lewy body, vascular dementia, and dementia not otherwise specified). History of depression, treatment for depression, and history of any mood disorders were noted. A careful history of the onset of PD and progression of the disease was obtained from the family, caregiver, and resident (where applicable), with particular attention to the onset of cognitive decline in relation to PD. These interviews, as well as the chart review, were used to clearly establish whether a subject’s onset of cognitive decline occurred at least 2 years after a diagnosis of PD. Residents were assessed for orientation, attention and concentration, memory, executive functioning, and visuospatial perception, which are parameters of impairment often present in PDD.6,7 Several of these parameters were assessed using the Mini-Mental State Examination (MMSE). Executive functioning was assessed using the clock drawing test. Residents were also assessed for depression using the abbreviated version of the Geriatric Depression Scale comprising 15 questions (GDS-15). Any resident who had a GDS-15 score of 7 or more was considered depressed and thus could not be assessed for PDD. The original criteria use a cutoff of 4 on the GDS as exclusion. This may give a high false-positive rate of depression and exclude people from the final sample. On the basis of clinical experience and literature reviews, a cutoff score of 7 was used as it had a good trade-off between sensitivity and specificity for the GDS. Anyone with an MMSE score of less than 26 was considered to have dementia and cognitive impairment. Any participant losing a point on the clock drawing test was thought of as having executive impairment. Attention and concentration were assessed using “serial sevens” or spelling “world” backwards, with two or more mistakes scored as positive for impaired attention and concentration. Failure to properly draw the intersecting pentagons on the MMSE was scored as positive for impaired visuospatial perception. Finally, one or more errors on three word recall defined memory impairment. Criteria and parameters for evaluation were adapted from the existing literature.4,8,9 PDD was diagnosed using the criteria shown in Figure 1. Data were analyzed using SPSS version 15. Descriptive statistics were computed regarding PD, PDD, and FDA-approved treatments for PDD.
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FIGURE 1. Parkinson’s disease dementia criteria.
RESULTS The sample consisted of 714 residents, nearly evenly distributed between three nursing homes in the Saint Louis metropolitan area. Of these, 55 residents had a chart diagnosis of PD. Thus, the prevalence of PD in these nursing homes was 7.7% (95% confidence interval [95% CI]: 6.0e9.9). Of the 55 residents with a diagnosis of PD, 37 (67.3%) participated in the study. Sixteen subjects were excluded from the sample because consent was not available either because the guardian was unreachable or more commonly the patient/family refused to consent to the study. Two participants were excluded because they were in an advanced stage of the illness and in an almost comatose condition. An assessment of their cognitive function was not possible. However, on the basis of the history given by the family or caregivers of these two participants, it is suspected that they were likely to have PDD. Table 1 shows the distribution of PD diagnoses for each nursing home evaluated. The study sample consisted of 37 residents. Residents were between the ages of 61 and 99 years with a mean age of 82.3 years. Twenty-three (62.2%) were women and 14 (37.8%) were men. Table 2 displays summary information for the cognitive and depression assessments. MMSE scores ranged from 9 to 30
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with a mean of 20.5 (SD ¼ 7.3). Thirty residents (81.1%) had impairments in memory, 24 (64.9%) had impairments in visuospatial construction, and 30 (81.1%) had impairments in executive function. GDS scores varied from 0 to 12 with a mean of 4.1 (SD ¼ 3.2). Twentynine (78.4%) participants had a GDS of less than 7, and 8 (21.6%) had GDS scores of 7 or more. On the same note, 23 (62.2%) participants had a chart history of depression and 2 had other mood disorders. Eight participants had a diagnosis of Alzheimer dementia and 17 had a diagnosis of other dementias. Within the total study sample, 29 (78.4%) participants were on anti-parkinsonian medications, 28 (75.7%) were on antidepressants, 12 (32.4%) were on medications for dementia other then rivastigmine, 4 (10.8%) were on rivastigmine, and 5 (13.5%) were on antipsychotics. A total of 18 of the 37 residents 48%; (95% CI: 33.5e64.1) with PD met criteria for PDD; however, 2 had a GDS score greater than 7 and were excluded from the diagnosis of PDD. Twenty of the 37 residents had onset of cognitive decline 2 years or more after onset of PD. The PDD group consisted of 10 (55.6%) women and 8 (44.4%) men. Among the residents who met criteria for PDD, 94.4% had impairments in executive functions and memory and 72.2% had impairments in visuospatial perception. Of the 18 subjects with PDD, 7 (38.9%) had a diagnosis of Alzheimer disease and another 7 (38.9%) had other dementias diagnosed in the chart. There were no residents who met criteria for PDD with a previous diagnosis of PDD. A full comparison of chart dementia diagnoses between the study group that fit criteria for PDD and the total study sample is seen in Table 3. Nine subjects with PDD had history of depression. As shown in Table 4, 13 (72.2%) subjects with PDD were on antidepressants, 16 (88.9%) were on antiparkinsonian medications, 7 (38.9%) were on anti dementia drugs other than rivastigmine, and 2 (11.1%) were on rivastigmine. Extrapolating the 48.6% prevalence of PDD to the 18 residents with PD who did not participate, the prevalence of PDD was estimated at 3.7% (95% CI: 2.6e5.5).
DISCUSSION PDD is a distinct form of dementia that occurs in the context of established PD. The prevalence of PDD
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Prevalence of PD and PDD in Community Nursing Homes
TABLE 1. PD Prevalence and Study Participation Across Nursing Homes Site 1 Total residents Residents with PD Nonparticipating PD residents Evaluable PD residents
243 18 3 15
(34%) (32.7%) (16.7%) (40.5%)
Site 2 212 20 8 12
(29.7%) (36.4%) (44.4%) (32.4%)
Site 3 259 17 7 10
Total
(36.3%) (30.9%) (38.9%) (27%)
714 55 18 37
TABLE 2. Cognitive Impairment and Depression in PD Group (N [ 37)
TABLE 4. Medications in Subjects Who Met Criteria for PDD (n [ 18)
Test
Medication
No. of Residents
Dementia (MMSE <26) Attention and concentration impairment (2 errors on Serial 70 s or Backwards WORLD) Executive impairment (1 error on clock drawing test) Visuospatial impairment (any error on intersecting pentagons) Memory impairment (1 error on the three word Recall) Depression (GDS-15 7)
26 (70.3%) 20 (54.1%) 30 (81.1%) 24 (64.9%) 30 (81.1%) 8 (21.6%)
TABLE 3. Chart Dementia Diagnoses in the PDD Group (n [ 18) versus Total PD Group (n [ 37) Chart Diagnosis Alzheimer disease Other dementia No diagnosis PDD
No. of Residents With PDD 7 7 4 0
(38.9%) (38.9%) (22.2%) (0%)
No. of Total residents 8 17 12 0
(21.6%) (45.9%) (32.4%) (0%)
was as high as 3.75% in this nursing home sample. No prior study has established the prevalence of PDD in nursing homes, thus there are no estimates for comparison. Of the subjects with PD, 48.65% met criteria for PDD, which is consistent with earlier estimates in the literature that range from 30% to 50%. The fact that this number is toward the higher end of the range (close to 50%) is likely because we sampled residents in nursing homes who would be expected to have a higher prevalence compared with the general population, given their advanced age and the level of care required in those who enter a nursing home (who tend to have more advanced PD upon admission). These risk factors, older age, duration of PD, and severity of parkinsonism, have been shown to impact the incidence of PDD.10e14 The design of this study relied on an existing chart diagnosis of PD. All chart diagnoses were documented using appropriate diagnostic criteria in a clinical setting by a board-certified primary care physician. These diagnoses were used as inclusion
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Rivastigmine Anti-PD Antidepressants Antidementia
No. of Residents 2 16 13 7
(11.1%) (88.9%) (72.2%) (38.9%)
criteria for the sake of our study and are understood as a limitation. Using an already established diagnosis may have missed residents with undiagnosed PD. At the same time, the charts reviewed were nursing home charts and though they contained clinical notes from the patient’s primary providers, they by no means are as reliable as a medical chart. We did not seek out a medical chart as it was outside what was permitted by the institutional review board. The nursing home charts were updated after every visit of the provider but there is likelihood of error in updating. This could affect the accuracy of the prevalence estimates. PD is a clinical diagnosis and there is the possibility of other Parkinson syndromes being labeled as PD. Our study was limited by the fact that we did not attempt to ascertain whether we were dealing with PD or one of the Parkinson syndromes. Reviewing the medical chart could reduce some of this error. This may be an interesting area for future research. The design of our study also established a “2-year rule,” where a clear timeline of PD diagnosis at least 2 years prior to development of cognitive decline must be present. This was used to ensure that cognitive decline described in subjects was confidently within the context of established PD. Although appropriate to establish criteria for the sake of our study, this rule can be considered an arbitrary distinction. The specific length of time that parkinsonism actually precedes cognitive decline has been shown to not correlate with pathological differences in patients.15 The final study sample consisted of 37 participants out of a total of 55 who were found to have PD. We excluded two participants from the study because
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Hoegh et al. they were in a comatose state and could not have participated in our clinical exam. Had they been included and met criteria for PDD the prevalence estimate would have gone up to 54%, this is likely based on caregiver history. In addition, it would be interesting to know how the 16 residents with PD who were excluded from the study because of failure to obtain consent would have affected the prevalence estimates, given that we do not know their clinical status. It is likely that they would have same rate of PDD, but there could be a selection bias. One could argue that the residents who refused consent may have had PD for a long time and so had advanced stage of the illness at which point they would not have seen the need to participate. This means that we could see a higher incidence of PDD and thus could have resulted in a higher prevalence than what we estimated. It could also be argued that the residents who refused consent had little or no cognitive decline at which point they would not have seen the need to participate. This would yield a lower incidence and could have resulted in a lower prevalence than what we estimated. The final study sample consisted of a total of 37 participants. Of these, 23 (62.2%) were women and 14 (37.8%) were men. National nursing home demographics estimate a total female distribution of 71.1%.16 Our study sample is consistent with this trend in gender distribution and thus allows for greater confidence when generalizing data from this study to the nursing home population as a whole. More importantly, gender alone is not considered a risk factor for PDD, whereas women with PD have been found to have a greater life expectancy, they have not been found to be a greater risk for PDD.17,18 Thus an unequal gender distribution would not alter the results of our study. The methods employed in our study also had some drawbacks. Major depression is an exclusion criterion for PDD. We estimated major depression using GDS15 with 7 as a cutoff for a major depressive episode. This is by no means a replacement for a clinical interview but GDS has proven to be an effective tool for depression in the geriatric population including people with PD.19 According to the original criteria, a score cutoff of 4 was used for exclusion due to depression. Although this has a high sensitivity, the specificity was low. On the basis of other studies, we employed a score cutoff of 7 on the GDS, which was
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an even trade-off between a slightly lower sensitivity and a higher specificity.20 We employed the clock drawing as a measure of executive dysfunction, yet we did not assess for decline in other areas of executive dysfunction such as lexical fluency. For assessing visuospatial orientation, we relied on the intersecting pentagon test. People with PD have some level of motor deficits and so it is hard to determine whether failure to draw the intersecting pentagon was visuospatial or motor in origin. Compared with the non-PDD group (51.6%), the PDD group had a higher percentage of residents with impairment in all four areas of tested cognitive functioning. Executive and memory impairment were more commonly affected among the PDD group as compared with the non-PDD group. History of depression was also more common in the non-PDD subgroup (73.7%) as opposed to PDD subgroup (50%). No participant in this study had a chart diagnosis of PDD. This, we believe, was because of a relative lack of awareness among primary care providers about PDD as a distinct entity, as well as a lack of awareness of the clinical implications of PDD. This finding is of significant clinical value because when the total absence of a PDD diagnosis in the chart is compared with the prevalence data found in our study, a large discrepancy is seen. This discrepancy establishes a need to educate and create awareness among primary care providers about PDD. Though we did not take into account who made the diagnosis of PD, a primary care provider or a neurologist, it certainly would be an interesting fact to know to assess whether there are any differences between the two groups in diagnosing PD and dementia syndromes. There were 8 (21.6%) participants with a diagnosis of Alzheimer disease and 17 (45.9%) participants with a diagnosis of other dementias (Lewy body, vascular dementia, and dementia not otherwise specified). The results showed a significant overlap among participants with a diagnosis of Alzheimer disease and those who met criteria for PDD. Seven of the eight participants with a chart diagnosis of Alzheimer disease met the criteria for PDD. This could be because of a high comorbidity of PD with Alzheimer disease or incorrect diagnosis of Alzheimer disease. The parameters for diagnosis of PDD used in this study included evaluations that separate Alzheimer disease and PDD on the basis of their cognitive impairment profiles. Past analyses comparing
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Prevalence of PD and PDD in Community Nursing Homes the profiles of cognitive impairment of AD or PDD have suggested that a diagnosis could be predicted from the cognitive profile alone with 74.7% accuracy.7 However, there were no significant differences in the cognitive profiles of our PDD group and the non-PDD group with dementia syndromes. This supports many previous studies that although there are differences in the cognitive profiles of individuals with PDD and AD, these are more apparent in early stages and thus making the distinction clinically can be challenging.7 Our sample ranged from mild cognitive impairment to severe and so could explain why we did not see any patterns in the decline in various cognitive domains between the PDD and AD groups. Although incorrect diagnosis could be a reason for the overlap seen, this distinction is not simple and the possibility of this comorbidity does limit our study. On the contrary, to the high overlap seen with Alzheimer disease, participants with a previous diagnosis of other dementias were fairly evenly distributed between the PDD(38.9%) and nonPDD (52.6%) subgroups. We did not account for and rule out other dementia syndromes such as vascular dementia and this is another limitation of our study. However, the prevalence of pure vascular dementia syndromes is fairly low and so we believe that it may not affect the results significantly. One can highlight the clinical implications and relevance of diagnosing PDD. Rivastigmine is a cholinesterase inhibitor and the only FDA-approved treatment for PDD with statistically significant treatment benefits.21,22 This would make it useful to differentiate PDD from other forms of dementias so as to guide the selection of the appropriate therapeutic agent. Because of its FDA-approved status, rivastigmine specifically was separated in our study from other cholinesterase inhibitors in an effort to distinguish treatment for PDD from general use of a cholinergic agent for other cognitive impairment. Among our subjects, 12 were on cholinesterase inhibitor medications other than rivastigmine (such as
donepezil) whereas 4 were on rivastigmine. Of the 18 subjects who met criteria for PDD, only 2 were on rivastigmine. It is possible that in these cases the clinician may have suspected the possibility of PDD or may just have been using rivastigmine as a cholinergic agent for cognitive impairment. There is also the possibility that some of these participants had been tried on rivastigmine and were unable to tolerate it and such were placed on another cholinesterase inhibitor as appropriate treatment for their suspected PDD. Also, rivastigmine has not specifically been shown in the literature as clearly superior to other cholinesterase inhibiting agents, there is the possibility of physician preference for another cholinesterase inhibitor. Because of these possibilities it is not possible to extrapolate that all 16 subjects who met criteria for PDD and were not on rivastigmine were being treated inappropriately. PDD remains unrecognized as a distinct entity and there is a high likelihood that it is diagnosed as another dementia syndrome. This may interfere in the choice of the most appropriate treatment agent.
CONCLUSION PDD is a distinct form of dementia in the presence of established PD. It can complicate the disease course in nearly half (48.65%) of the residents with PD. It has a prevalence of up to 3.7% among residents in the nursing homes represented in this research. It remains an unrecognized entity among primary care providers as shown by our study. In addition, PDD is largely treated as other types of dementia. It is important to be mindful of this entity and to educate and create awareness among primary care providers about PDD. Dr. Grossberg serves as a consultant to Novartis Pharmaceuticals and his institution has received research funding from Novartis.
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