The behavioral and psychological symptoms of dementia (BPSD) are common and serious problems that affect the quality of life of the patients who experience such symptoms as well as their caregivers (Matsui et al., Reference Matsui2006). BPSD present a major challenge in the medical management of cognitively impaired patients. Our paper entitled “Behavioral disorders and caregivers’ reaction in Taiwanese patients with Alzheimer's disease” (hereafter referred to as the “paper”) (Fuh et al., Reference Fuh, Liu, Mega, Wang and Cummings2001) has been cited widely, reflecting the importance of these clinical issues and the growing international interest in studies of BPSD.
A valid and reliable evaluating instrument is essential to detect and study BPSD. The aims of the paper were to evaluate the applicability of the Chinese (Taiwanese) version of the Neuropsychiatric Inventory (NPI) (Cummings et al., Reference Cummings1994), and to explore the neuropsychiatric manifestations of Taiwanese patients with Alzheimer's disease (AD) and the associated caregiver distress (Fuh et al., Reference Fuh, Liu, Mega, Wang and Cummings2001). The NPI was developed to assess psychopathology in dementia patients and is one of the most commonly used instruments to evaluate BPSD. It evaluates 10 neuropsychiatric disturbances often observed in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition and aberrant motor behavior. The night-time behavior disturbances and appetite and eating abnormalities were added to the NPI later (NPI-12) (Cummings, Reference Cummings1997). A nursing home version also was developed for use by professional caregivers within institutions (Wood et al., Reference Wood2000). The severity and frequency of each neuropsychiatric symptom are rated on the basis of scripted questions administered to the patient's caregiver. The NPI also assesses caregiver distress engendered by each of the neuropsychiatric disorders. The NPI provides a clear and simple description of each symptom and assists researchers and clinicians to better define each symptom of BPSD. The high cross-cultural reliability of the NPI is based on its highly structured format and scripted questions.
We have reviewed the 32 articles that cited our paper and discovered that 18 of them (56.2%) found the paper of interest because it provided evidence of the existence of neuropsychiatric sub-syndromes in dementia. Six articles (18.9%) cited the paper because of cross-cultural comparisons of BPSD, a growing area of interest in dementia and BPSD research.
BPSD refers to a heterogeneous range of psychological reactions, psychiatric symptoms, and behaviors occurring in people with dementia. Factor analysis techniques have been used to explore behavioral dimensions that may comprise BPSD. Table 1 summarizes studies using factor analytic techniques to identify the subsyndromes contained within the NPI (Frisoni et al., Reference Frisoni1999; Fuh et al., Reference Fuh, Liu, Mega, Wang and Cummings2001; Aalten et al., Reference Aalten2003; Lange et al., Reference Lange, Hopp and Kang2004; Mirakhur et al., Reference Mirakhur, Craig, Hart, Mcllroy and Passmore2004; Borroni et al., Reference Borroni2006; Hollingworth et al., Reference Hollingworth2006; Matsui et al., Reference Matsui2006; Aalten et al., Reference Aalten2007; Zuidema et al., Reference Zuidema, de Jonghe, Verhey and Koopmans2007). Three to five sub-syndromes were found in these studies and different terms were used to label them. Despite some differences among these studies, the associations of the following symptoms were very consistent: (1) depression and anxiety, (2) delusions and symptoms of hallucination, (3) agitation and irritability, (4) disinhibition and euphoria. The symptoms were in the same sub-syndrome in most of the reviewed studies and across various cultural settings, suggesting that these four common sub-syndromes may reflect four distinctive pathophysiological disorders (Robert et al., Reference Robert2005). More studies are needed to determine if these four sub-syndromes also share treatment-related characteristics.
Table 1. Results of previous factor analytic studies using the NPI
Apathy and aberrant motor activities are two symptoms that had variable associations with other individual symptoms in different patient populations. Apathy was associated with depression in some studies (Aalten et al., Reference Aalten2003; Reference Aalten2007; Hollingworth et al., Reference Hollingworth2006), with aberrant motor activities in others (Frisoni et al., Reference Frisoni1999; Lange et al., Reference Lange, Hopp and Kang2004; Mirakhur et al., Reference Mirakhur, Craig, Hart, Mcllroy and Passmore2004; Matsui et al., Reference Matsui2006; Zuidema et al., Reference Zuidema, de Jonghe, Verhey and Koopmans2007), or with other symptoms in some studies (Fuh et al., Reference Fuh, Liu, Mega, Wang and Cummings2001; Borroni et al., Reference Borroni2006; Zuidema et al., Reference Zuidema, de Jonghe, Verhey and Koopmans2007). The relationship between depression and apathy is controversial. It is recognized that apathy overlaps with depression, which is not surprising considering that common symptoms of both syndromes include diminished motivation and interest as well as lack of insight. The major difference is that apathy may occur in the absence of depressed mood. One study showed that the associations of apathy with depression changed as the disease progressed (Hollingworth et al., Reference Hollingworth2006), possibly explaining some conflicting study results. Studies using positron emission tomography (PET) and single emission computed tomography (SPECT) to establish regional cerebral metabolism or perfusion showed that regions of dysfunction associated with these two syndromes were different. Patients with apathy showed involvement of the anterior cingulate and related frontal-subcortical circuit structures (Craig et al., Reference Craig1996; Benoit et al., Reference Benoit1999), patients with depression evidenced more abnormalities of frontal, temporal and parietal areas (Starkstein et al., Reference Starkstein, Vazquez, Migliorelli, Teson, Sabe and Leiguarda1995; Hirono et al., Reference Hirono1998).
Aberrant motor activities had no consistent associations with any individual symptoms. Aberrant motor activities comprise symptoms like pacing, constant opening/closing wardrobes, repeatedly dressing or undressing and picking/fiddling or other repetitive behavior (Cummings et al., Reference Cummings1994). This syndrome is least well understood of all those identified by the NPI and warrants further study.
BPSD no doubt stem from a complex interaction among biological, environmental and cultural factors (Fuh et al., Reference Fuh, Mega, Binetti, Wang, Magni and Cummings2002). Similar behavioral sub-syndromes identified across different cultures suggests that the observed behaviors are more related to a common underlying biological dysfunction whereas differing patterns of behavior may indicate that cultural or environmental influences may be more relevant. Our previous transcultural study (Fuh et al., Reference Fuh, Mega, Binetti, Wang, Magni and Cummings2002) of three countries – Taiwan, Italy and the U.S.A. – showed a significant relationship between agitation and hallucinations in the Taiwanese group and a significant relationship between agitation and apathy in the Italian group. In the American group, agitation and irritability were associated. We found different behavioral profiles accompanying agitation in the three cultural groups. This study highlighted the importance of cultural factors in some symptoms of BPSD.
Many transcultural questions pertaining to dementia remain unanswered, and there is a relative paucity of research on dementia in non-Western societies. The conduct of cross-cultural studies using standardized sampling, diagnostic and assessment methods could contribute to our understanding of the interplay between genetic and environmental risk factors. Including our Chinese version, the NPI has been translated into a variety of languages with proven validity and reliability (Hirono et al., Reference Hirono1997; Binetti et al., Reference Binetti1998; Choi et al., Reference Choi, Na, Kwon, Yoon, Jeong and Ha2000; Fuh et al., Reference Fuh, Liu, Mega, Wang and Cummings2001; Leung et al., Reference Leung, Lam, Chiu, Cummings and Chen2001; Baiyewu et al., Reference Baiyewu2003; Lange et al., Reference Lange, Hopp and Kang2004; Politis et al., Reference Politis, Mayer, Passa, Maillis and Lyketsos2004; Camozzato et al., Reference Camozzato2008, Selbæk et al., Reference Selbæk, Kirkevold, Sommer and Engedal2008), facilitating further transcultural study of BPSD.
This study followed a period during which Dr. Fuh trained with Dr. Cummings at UCLA. Dr. Fuh became familiar with research strategies and approaches involving the NPI and related assessments. Successful implementation of these skills in Taiwan resulted in the study documented in the paper. Such cross-national training is essential to enhance research worldwide.
Many new agents are evolving for the treatment of AD (Salloway et al., Reference Salloway, Mintzer, Weiner and Cummings2008). To build sufficient sample size to test these agents, global trials will be required. Cross-cultural studies of instruments such as those conducted with NPI are critically important to designing and interpreting the data from these trials.
As Fuh and Cummings point out above, it is no coincidence that their paper (Fuh et al., Reference Fuh, Liu, Mega, Wang and Cummings2001) was equal sixth in the number of citations received by all papers published in International Psychogeriatrics to the end of 2006 with 31 citations. This is because BPSD encompass key elements of the dementia syndrome and are prime drivers of major shifts in care and treatment. To underline the initial point, the first patient with Alzheimer's disease ever to be described, Augusta D, had prominent agitated behavior and intermittent delusional ideas (Maurer et al., Reference Maurer, Cummings, McKeith, Ames and Burns2006). To address the second point, very few people with dementia get admitted to residential care because they cannot remember the date, and even fewer are prescribed antipsychotic drugs because they cannot spell “world” backwards. Behaviors whose expression is captured by the NPI, such as sleep disturbance, excess motor activity and resistiveness to care, are common reasons for dedicated family members to acknowledge with reluctance that they can no longer care for the person they love at home and to seek that person's admission to residential care. Delusions, hallucinations, misidentifications and aggressive behavior are frequent indications leading to the prescription of antipsychotic drugs, which have the potential both to help and to harm patients (Suh, Reference Suh2009) and the NPI is designed to note the presence, intensity and caregiver distress produced by these symptoms. The importance and topicality of this area of research is illustrated by a quick flick through the last three years of this journal's regular issues from December 2006 to October 2009 (18 issues). Of 48 review articles published over this period, ten (20.8%) (Filan and Llewellyn-Jones, Reference Filan and Llewellyn-Jones2006; Lyketsos, Reference Lyketsos2007; Konovalov et al., Reference Konovalov, Muralee and Tampi2008; von Gunten et al., Reference von Gunten, Alnawaqil, Abderhalden, Needham and Schupbach2008; Beaulieu-Bonneau and Hudon, Reference Beaulieu-Bonneau and Hudon2009; Haw et al., Reference Haw, Harwood and Hawton2009; Kverno et al., Reference Kverno, Black, Nolan and Rabins2009; O'Connor et al., Reference O'Connor, Ames, Gardner and King2009a; Reference O'Connor, Ames, Gardner and King2009b; Rodda et al., Reference Rodda, Morgan and Walker2009) dealt with some aspect of the BPSD spectrum in people with cognitive impairment, while 26 of 233 original research articles (11.2%) (Holmes et al., Reference Holmes, Knights, Dean, Hodkinson and Hopkins2006; Lövheim et al., Reference Lövheim, Sandman, Kallin, Karlsson and Gustafson2006; Reference Lövheim, Sandman, Karlsson and Gustafson2008; Reference Lövheim, Sandman, Karlsson and Gustafson2009a; Reference Lövheim, Sandman, Karlsson and Gustafson2009b; Svansdottir and Snaedal, Reference Svansdottir and Snaedal2006; Bird et al., Reference Bird, Llewellyn-Jones, Korten and Smithers2007; Davison et al., Reference Davison, Hudgson, McCabe, George and Buchanan2007; Kessing et al., Reference Kessing, Harhoff and Andersen2007; Lanctôt et al., Reference Lanctôt, Herrmann, Rothenburg and Eryavec2007; Liu et al., Reference Liu, Wang, Lin and Liu2007; Rabinowitz et al., Reference Rabinowitz, Katz, De Deyn, Greenspan and Brodaty2007; Cankurtaran et al., Reference Cankurturan, Kutluer, Senturk, Erzin, Gursay and Tombak2008; Haw et al., Reference Haw, Stubbs and Yorston2008; Nakaaki et al., Reference Nakaaki2008; Rozzini et al., Reference Rozzini2008; Treiber et al., Reference Treiber2008; Borroni et al., Reference Borroni, Alberici, Agosti, Cosseddu and Padovani2009; Burns et al., Reference Burns, Allen, Tomenson, Duignan and Byrne2009; Eggermont et al., Reference Eggermont, de Vries and Scherder2009; Kleijer et al., Reference Kleijer2009; Nijk et al., Reference Nijk, Zuidema and Koopmans2009; van der Geer et al., Reference van der Geer, Vink, Schols and Slaets2009; Weamer et al., Reference Weamer2009; Woods et al., Reference Woods, Bushnell, Kim, Geschwind and Cummings2009; Wu et al., Reference Wu, Low, Xiao and Brodaty2009) also focused upon BPSD in dementia and related conditions in some shape or form.
Because dementia is a global challenge of rapidly growing proportions, and one that is growing fastest in the developing world (Ferri et al., Reference Ferri2005), we need translations of instruments which will be useful in populations whose languages are not those of the instruments’ original designers, most of whom have developed their tools to be used in the English language. Again, International Psychogeriatrics illustrates this point. Since December 2006, 20 original research articles (Hendrie et al., Reference Hendrie2006; Awata et al., Reference Awata2007; Chachamovich et al., Reference Chachamovich, Trentini and Fleck2007; Falk et al., Reference Falk, Persson and Wijk2007; Malakouti et al., Reference Malakouti, Fatollahi, Mirabzadeh and Zandi2007; Nuevo et al., Reference Nuevo, Mackintosh, Gatz, Montorio and Loebach Wetherell2007; Tsai et al., Reference Tsai, Lin, Wang and Liu2007; Camozzato et al., Reference Camozzato2008; Chaaya et al., Reference Chaaya2008; Chu and Chung, Reference Chu and Chung2008; Leung et al., Reference Leung, de Jong and Lam2008; Selbæk et al., Reference Selbæk, Kirkevold, Sommer and Engedal2008; Skjerve et al., Reference Skjerve2008; van der Roest et al., Reference van der Roest, Meiland, van Hout, Jonker and Dröes2008; Dodge et al., Reference Dodge, Meguro, Ishii, Yamaguchi, Saxton and Ganguli2009; Fernandes et al., Reference Fernandes2009; Gibbons et al., Reference Gibbons2009; Perrocco et al., Reference Perrocco2009; Tiwari et al., Reference Tiwari, Tripathi and Kumar2009; Wong and Fong, Reference Wong and Fong2009), representing 8.6% of all such articles published in the journal that address the translation or validation of rating scales or assessment instruments in languages other than English, have been published within these pages. The International Psychogeriatric Association (IPA) exists partly in order to promote the spread of knowledge and to enable dissemination of best practice in order to benefit everyone in the world in relation to mental health and illness in late life, no matter where they live. Fuh et al. illustrated in their article the importance of this activity, and it is no coincidence that it has been highly cited. Its continued frequent citation is one illustration of the fact that IPA's journal continues to fulfill at least some of the objectives of IPA's founders and their successors
