Telemedicine, dementia and Down syndrome: Implications for Alzheimer disease

Alzheimer’s & Dementia 2 (2006) 179 –184

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Telemedicine, dementia and Down syndrome: Implications for Alzheimer disease Ira T. Lott,a,* Eric Doran,a David M. Walsh,b Mary Ann Hillc a Department of Pediatrics and Neurology, University of California, Irvine, CA, USA Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA c Alzheimer Disease Research Center, Institute for Brain Aging and Dementia, University of California, Irvine, CA, USA b

Abstract

Background: Individuals with Down syndrome (DS) who are at risk for dementia of the Alzheimer type (DAT) often live at sites remote from major medical centers. Telemedicine (TM) is a modality for providing medical care at remote locations but is underutilized for populations with Alzheimer disease (AD). Methods: We studied the feasibility of using TM to evaluate symptoms of DAT in 90 individuals with DS. Dementia was assessed by an informant questionnaire, a direct measure of praxis, pathological reflexes on the neurologic examination, and the presence of cortical atrophy on a neuroimaging procedure. The neurologist was blinded to the scores on neuropsychological measures. Differences in average cognitive scores between a TM and traditional academic medical center– based clinic site (TAC) were tested using 2-way analysis variance with site and premorbid IQ as factors. Logistic regression was used to explore the relationship, in addition to the cognitive scores, of influences such as age, premorbid IQ, and site to the prediction of the physician’s diagnosis of dementia. Results: Components of the neurologic, imaging, and neuropsychological examinations differentiated subjects with and without DAT (pⱕ0.008) irrespective of whether a subject was evaluated at a TM or TAC site. Conclusions: It is feasible to make a diagnosis of DAT in DS by TM. This study supports the need for formal reliability and validity studies of TM preparatory to the consideration of this modality for use in clinical trials for AD. © 2006 The Alzheimer’s Association. All rights reserved.

Keywords:

Down syndrome; Alzheimer disease; dementia; telemedicine; neurologic examination; cognitive testing

1. Introduction Access to medical care for individuals with Alzheimer disease (AD) has been cited as a major public policy concern in the United States [1] and Europe [2]. There may be a particular burden for caretakers of cognitively impaired adults living in rural environments remote from academic medical centers [3]. Telemedicine (TM) has been defined as the use of electronic information and communication technologies to provide patient care when distance separates the participants [4]. Despite decreasing costs and rapidly ex*Corresponding author. Tel.: 714-456-5333; Fax: 714-456-8466. E-mail address: [email protected]

panding technologies in interactive video, the application of TM to individuals with dementia remains underutilized, and studies of feasibility are needed. Down syndrome (DS) may provide a model for intervention in AD because individuals with DS are at increased risk for dementia of the Alzheimer type (DAT) [5]. The cognitive changes associated with premature senescence in DS have been identified as an underrecognized health problem for people with mental retardation [6]. Individuals with DS often reside in small residential settings that are remote from specialty physician access. People with DS who have DAT may benefit from treatment interventions so that early diagnosis is essential [7,8]. A current research strategy for the National Institute of Aging is focused on reducing health

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Table 1 Sample characteristics by examination modality

Gender Male Female Age, mean (SEM) Intellectual disability Mild – moderate (45 to 70) Low moderate (35 to 44) Severe – profound (⬍ 35) Neuropsychological testing DMR-SOS, mean (SEM) DMR-SCS, mean (SEM) BPT, mean (SEM) Diagnosed with DAT

Telemedicine Sites (n ⫽ 61)

Typical Academic Center (n ⫽ 29)

66% 34% 51.4 (0.75)

45% 55% 49.7 (1.25)

21.3% 19.7% 59.0%

55.2% 24.1% 20.7%

19.4 (1.40) 24.4 (1.30) 61.3 (3.17) 32.8%

17.8 (2.06) 21.2 (2.24) 62.0 (3.27) 27.6%

disparities by developing new approaches to the diagnosis and treatment of dementia [9]. TM may serve as one of the new strategies. There have been a few studies in which other neurologic disorders have been assessed and treated by TM. In Northern Ireland, teleneurology has been shown to be suitable for outpatient work and has been associated with a shorter hospital course for patients with neurologic disorders [10 – 12]. Lee et al [13] utilized a TM care modality system for dementia in Korea and reported a favorable consistency rate of assessment by this method in comparison with a traditional “face-to-face” examination. Administration of the Cambridge Cognitive Examination, a measure of dementia, has been shown to be reliably administered by videoconferencing [14]. Saligari et al [15] assessed the validity of conducting geriatric cognitive assessments via videoconferencing and found a high correlation between the scores from a “face-to-face” assessment and those from videoconferencing. In the area of stroke, TM has been shown to be a feasible and promising method to improve care in rural areas where acute management is hindered by long transportation distances [16 –18]. The use of the National Institutes of Health stroke scale showed high inter-rater correlations between scores obtained by interactive video in comparison with a traditional clinic setting [17]. TM has also been shown to be a useful modality in following up with patients with Parkinson’s disease [18]. The special needs of children with neurodevelopmental disabilities have been addressed successfully by TM [19]. In an editorial, Brown [20] has concluded that teleneurology is associated with satisfactory clinical outcomes but that more research application is needed. The current study was designed to determine the feasibility of using TM to diagnose DAT in remote populations of individuals with DS and to compare aspects of the diagnostic process with those used in a traditional “face-to-face” academic medical-center based clinic site (TAC).

2. Methods The TM sites were located 145 to 300 miles away from our TAC, the site from which the remote neurologic examinations were conducted. Both rural and urban sites were represented in the TM clinics. The TM sites were maintained by 2 regional centers for the developmentally disabled serving individuals residing near the cities of Bakersfield (Kern Regional Center), Visalia, Fresno, and Merced (Central Valley Regional Center), California. The TAC site was located at University of California, Irvine Medical Center serving Orange County, California. Adults with DS 40 years or older (n ⫽ 293) were screened for dementia utilizing the Dementia Questionnaire for Mentally Retarded Persons (DMR) [21]. When adjustment is made for premorbid intelligence quotient levels (IQ), DMR scores differentiate between demented and nondemented subjects. In this informant measure, “normally yes,” “sometimes,” or “normally no” answers are given to 50 items covering 8 areas of cognitive and emotional functioning. The results are summarized as the Sum of Cognitive (SCS) or Sum of Social (SOS) scores with higher scores indicating more severe impairment. Individuals 40 years or older with DS were screened for the study because the occurrence of dementia under this age is very unusual [22]. The DMR was administered to the subjects’ care providers by nurses or case managers who were trained by clinical psychologists. Score interpretation was made by a clinical psychologist at each site. Training of the nurses and case managers was accomplished by TM and verified by an on-site examination. Subjects with DS who met screening criteria for dementia on the DMR or whose low level of cognitive functioning precluded use of the instrument were referred for further evaluation at either the TM or the TAC (n ⫽ 90). These patients comprised 66% men at the TM sites and 45% men at the TAC site (Table 1). After the DMR screening, the subjects were evaluated by the neurologist and then given

I.T. Lott et al. / Alzheimer’s & Dementia 2 (2006) 179 –184

DMR-SCS DMR-SOS BPT

Site

Premorbid IQ

Interaction

0.738 0.452 0.594

0.004 0.066 0.006

0.802 0.135 0.995

the Brief Praxis Test (BPT; see below). The mean age at the TM sites was 51.4 years (SEM, 0.75) and the age at the TAC was 49.7 years (SEM, 1.25). Participants were drawn almost equally from Kern Regional Center (35.6%), Central Valley Regional Center (32.2%), and the TAC (32.2%). A clinical diagnosis of DAT was established according to the criteria listed in the Diagnostic and Statistical Manual of Mental Disorders– 4th Edition (DSM-IV) [23]. Along with the neuropsychological measures utilized, the criteria for diagnosing dementia conform to those suggested by Burt et al [24]. The same neurologist was responsible for the diagnosis at both the TM and TAC sites and examined all of the subjects in the study. A neurologic history from the caretaker and an examination was carried out, independent of the neuropsychological testing. The differential diagnosis included depression, sensory deficits, and other manifestations that could mimic dementia. In using the DSM-IV criteria, attention was given to symptomatic change from baseline because individuals with intellectual disabilities vary in their cognitive and functional skill levels. Examination of pathologic reflexes associated with DAT including grasp, sucking, snout, and palmomental reflexes were carried out according to Adams and Victor [25]. The examining neurologist was blind to the scores on all of the neuropsychological measures. A diagnosis of cortical atrophy on either computed tomography (CT) or magnetic resonance imaging (MRI) brain scans was made by a board-certified radiologist. At the time of clinical evaluation, each subject was given the BPT [26], a measure of praxis in which the items are selected according to age-appropriate relevance to the behavior repertoire of adult persons functioning at mild to profound levels of intellectual disability. All of the items in the BPT meet the following criteria: (1) requiring only a few seconds to perform on verbal request; (2) easy to administer, score, and record; and (3) sampling behaviors that would be expected to occur normally in daily life of the individual with developmental disabilities (eg, hand clapping, standing on one foot, salute, opening and closing a jar). The BPT is a direct measure in which the scores are inversely related to the severity of dyspraxia, a cardinal symptom of the DAT process in DS. The BPT was administered by nurses at each site. Research approval was granted by the Institutional Review Board of the University of California, Irvine.

2.1. Telemedicine equipment and procedures The TM system comprised a Polycom Model H323 View Station unit, a 32-inch high-resolution video monitor. The system provided 384 kilobits per second of video bandwidth at 30 frames per second. Interactive video and audio utilized the Integrated Services Digital Network signal format over 3 standard twisted pair telephone lines. The TM examination comprised a 2-way interactive television interview with video conferencing at both ends. This allowed a “real-time” interaction to take place between the neurologist and technician at one location and the patient, guardian/caretaker, and nurse at the other location. 2.2. Data analyses The differences between TM and TAC sites in average DMR-SCS, DMR-SOS, and BPT scores were tested using 2-way analysis of variance (ANOVA) with site and premorbid IQ as factors. Logistic regression was then used to explore the relationship, in addition to the cognitive scores, of influences such as age, premorbid IQ, and site to the prediction of the physician’s diagnosis of dementia. Chisquare tests were utilized for nominal variables. Statistical analyses were completed using SYSTAT (SYSTAT Software Inc, Richmond, CA) and BMDP (Statistical Solutions, Saugus, MA). 3. Results 3.1. Agreement between TM and TAC sites The demographics of the study population in the TM sites are compared with the TAC site in Table 1. There were 35 DMR-SCS Average Score

Table 2 Significance levels for neuropsychological tests by site and premorbid IQ

181

28 21 14 SITE

7

TM Traditional

0 ld Mi

/M

od Lo

w

Mo

d Se

r v /P

o fo

un

d

Premorbid IQ Fig. 1. Cognitive scores stratified by premorbid IQ at TM versus traditional clinic (TAC) site. Higher scores indicate greater cognitive impairment. (DMR-SCS: Dementia Questionnaire for Persons with Mental Retardation Sum of Cognitive Score; DMR-IQ: DMR Intelligence Quotient [IQ] Levels; Mild/Mod: DMR-IQ Scores 45-70; Low Mod: DMR-IQ Scores 35-44; Sev/Profound: DMR-IQ Scores below 35.)

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BPT Average Score

75

50

25 SITE TM Traditional 0 ld Mi

/M

od w Lo

Mo

d Se

v/

o Pr

fo u

nd

Premorbid IQ Fig. 2. Praxis scores stratified by premorbid IQ at TM versus traditional clinic (TAC) site. Lower scores indicated more severe impairment of praxis. (BPT: Brief Praxis Test; DMR-IQ: Dementia Questionnaire for Persons with Mental Retardation Intelligence Quotient [IQ] Levels; Mild/ Mod: DMR-IQ Scores 45-70; Low Mod: DMR-IQ Scores 35-44; Sev/ Profound: DMR-IQ Scores below 35.)

no significant differences in age and gender between sites. No differences between TM and TAC sites were detected for the DMR-SCS, DMR-SOS, and BPT average scores. Analyses were stratified by premorbid IQ because more low-IQ subjects were evaluated at TM sites. More than 50% of the subjects at the TM sites were in the severe to profound range of developmental disability, whereas only 21% of the subjects at the TAC site showed the same severity of disability. The 2-way ANOVA results shown in Table 2 indicate that there were no site effects for any of the neuropsychological measures. For the DMR-SCS (Fig. 1) and the DMR-SOS, both the site effects and interactions with premorbid IQ were not significant. No site differences or interactions with premorbid IQ were identified for average BPT scores (Fig. 2). 3.2. Cognitive scores, clinical observations, and dementia diagnosis The proportions of subjects diagnosed with DAT were not significantly different between TAC (27.6%) and TM (32.8%) sites (p ⫽ 0.618).

Components of the neurologic and neuropsychological examinations differentiated subjects with and without DAT (Table 3). Subjects without DAT were found to have nondementia behavioral disturbances (29.0%), seizures unrelated to dementia (1.6%), or independent movement disorders (1.6%). A pseudodementia was found in 6.5% of patients characterized either by sensory losses, systemic illness, or medication toxicity. When further examined, the remaining non-DAT patients (61.3%) were found to have no significant changes from baseline functioning. On the BPT, subjects with DAT exhibited a lower mean (more impaired) score than those without DAT (p ⫽ 0.008). On the DMR-SCS, subjects with DAT had higher (more impaired) average scores than subjects without DAT (p ⫽ 0.006). The DMR-SOS scales did not show significant differences between the DAT and non-DAT subjects. Pathologic reflexes were present in 89.7% of the DAT group compared with only 7.8% of the non-DAT group (p ⫽ 0.001). Cortical atrophy was detected for 89.3% of the DAT group that had scans, whereas 21.4% of the non-DAT group showed cortical atrophy (p ⫽ 0.001). The type of examination did not exert an effect on the prevalence of DAT or neurologic observations, such as pathologic reflexes and cortical atrophy. Computed tomography (CT) scans were more frequently recommended to subjects examined by TM (p ⫽ 0.008), whereas MRI scans were more commonly recommended to subjects seen at the TAC site (p ⫽ 0.001). Logistic regression was used to explore additional influences contributing to the prediction of dementia, such as age, premorbid IQ, and site. When these variables were used in combination with DMR-SCS, DMR-SOS, or BPT, the fit of the model was not enhanced. When these variables were used as single predictors of the neurologist’s diagnosis of DAT, none of the resulting odds ratios were significant. The largest percentage of correct classification was achieved using BPT alone. With this model, 78.3% of the subjects were classified correctly. Sensitivity (for a positive DAT diagnosis) and specificity were, respectively, 0.813 and 0.773. That is, more than 80% of those with DAT diagnosed by the physician were predicted to have DAT using the BPT examination model. The area under the corresponding receiver operating characteristic curve was 0.807 and the odds ratio was 14.7 (confidence interval: 3.5, 62.2).

Table 3 Neuropsychological and neurologic differences by diagnosis for combined TM and TAC sites for the 90 subjects studied Clinical Findings Neuropsychological Results, mean (SEM) DMR-SCS DMR-SOS BPT Abnormal neurologic observations, % Cortical atrophy Pathologic reflexes

DAT (n ⫽ 28)

No DAT (n ⫽ 62)

Significance p

27.9 (1.62) 21.7 (2.11) 51.6 (3.64)

21.3 (1.41) 17.6 (1.36) 65.2 (2.65)

0.006 Nonsignificant 0.008

89.3 89.7

21.4 7.8

0.001 0.001

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4. Discussion These results show that it is possible to make a diagnosis of DAT in DS irrespective of whether the patient is evaluated in a TM or a TAC setting and that an independent neurologic diagnosis was consistent with neuropsychological, neurologic, and imaging measures of DAT severity. This was a feasibility study in which the aim was to demonstrate achievability of carrying out a TM evaluation for dementia in DS. The study was not designed to determine reliability, validity, or cost effectiveness of the TM modality, which would be the next step in evaluation. It appears likely that all individuals older than 40 years with DS were screened in the respective populations, because the potential subject lists were screened by the respective Regional Centers utilizing their own database. Subjects from the TM sites were found to have higher measures of intellectual impairment at the time of enrollment into the study. In part, this difference was secondary to lower premorbid IQ scores among subjects at the TM versus the TAC site. Also, it appears likely that the diagnosis of DAT at the TM sites was made at a later time in the course of the illness than that observed in the TAC setting. Within the TM setting, CT brain scans were completed more often than MRI studies, likely based on the difficulties involved in patient cooperation for the latter studies at rural community hospitals. Although cortical atrophy was significantly more frequent in the DAT population, 21.4% of patients considered clinically non-DAT had readings of cortical atrophy. Cortical atrophy on CT scans has been reported in patients without DAT in the general population [27]. Cortical atrophy has been correlated with the presence of white matter hyperintensities (WMH) in typical subjects [28]. We have shown WMH to be more frequent with age in DS [29]. The use of the DMR as an informant measure and the BPT as a direct measure conforms to the recommendations of Aylward and Burt [30] suggesting that both informant and direct measures are useful in the diagnosis of DAT in DS. The DMR is more sensitive and specific when used as a longitudinal measure, but absolute cutoff scores have been provided for a single measurement that can detect wellestablished dementia. In a study conducted in a sample of adults with DS, Deb and Braganza [31] found that the specificity and sensitivity of the DMR compared with an independent clinical diagnosis of DAT was 0.92 for both categories. In our study, the SCS but not the SOS scores differentiated the clinical diagnosis of DAT. Deb and Braganza [31] have noted that in contrast to the memory items on the DMR, the behavior variables, such as those measured on the SOS subscales, may be less specific for DAT in DS, particularly in the early stages of the disease. The DMR was not designed to be used within the population of profoundly impaired individuals with intellectual disability, but even in this highly impaired group, there was a significant correlation with an independent neurologic diagnosis of dementia.

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Impairment or deterioration in praxis consists of a partial loss of the ability to perform purposeful or skilled motor acts in the absence of paralysis, sensory loss, abnormal posture or tone, abnormal involuntary movements, incoordination, poor comprehension, or inattention [32]. Although praxis skills may be well developed in children with DS [33], there is a marked decline in these abilities with age and the onset of dementia [34,35]. Gait apraxia is occasionally seen as part of a cortico-basal degeneration in AD and other dementias [36]. Our logistic regression analyses indicated BPT was the most effective predictor of DAT in DS. Although we did not conduct a formal study of process, the services provided to individuals with DS appeared to have been well received by the consumers, care providers, and health care professionals. There were no technical problems in carrying out the TM examination aside from rare telephone line outage during a lightening storm. In a review of clinical outcomes in TM, consumer satisfaction was reported to be high (80% or greater), particularly when travel over long distances was required to receive commensurate care [37]. To our knowledge, this study is the first attempt to diagnose DAT in DS by use of TM. Efficacy in diagnosing DAT in remote populations of individuals with DS supports the possibility of utilizing TM for clinical intervention trials for DAT in both DS and the general population once further studies of reliability and validity are carried out. Acknowledgments Supported in part by National Institutes of Health (RO1AG21912: “Alzheimer’s Disease in Down Syndrome: Antioxidant Trial”; P50-AG16573: “Down syndrome subcore of the Alzheimer’s Disease Research Center of the University of California, Irvine”); Department of Developmental Services, State of California (RCOC 30552: “Early Diagnosis and Treatment of Alzheimer’s Disease in Down Syndrome: A Telemedicine Feasibility Model”), and My Brother Joey Clinical Neuroscience Fund at the University of California, Irvine. References [1] Small GW, Rabins PV, Barry PP, Buckholtz NS, DeKosky ST, Ferris SH, et al. Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s Association, and the American Geriatrics Society. JAMA 1997;278(16):1363–71. [2] Rimmer E, Stave C, Sganga A, O’Connell B. Implications of the Facing Dementia Survey for policy makers and third-party organisations across Europe. Int J Clin Pract Suppl 2005; March(146):34 – 8. [3] Bedard M, Koivuranta A, Stuckey A. Health impact on caregivers of providing informal care to a cognitively impaired older adult: rural versus urban settings. Can J Rural Med 2004;9(1):15–23. [4] Czaja SJ, Rubert MP. Telecommunications technology as an aid to family caregivers of persons with dementia. Psychosom Med 2002; 64(3):469 –76.

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