Muhammad Nasar Sayeed Khan
Associate Professor and Head, Department of Psychiatry Services, Institute of Medical Sciences, Services Hospital, Lahore, Pakistan.
Introduction: Persons with Alzheimer’s disease (AD) demonstrate a range of behavioural and psychological symptoms of dementia (BPSD). The description of these symptoms in AD patients will improve treatment. The aim of this study is to describe these symptoms and to correlate it with the severity of the disease.
Method: A cross-sectional observational study was conducted at a tertiary care centre in Lahore. Patients suffering from AD diagnosed on the basis of DSM-IV were included. Demographic and clinical data was collected and dementia severity was assessed with the Mini Mental State Examination (MMSE - mild 27-21, moderate 20-11, severe ≤ 10). The behavioural symptoms reported by the patients were recorded using semi-structured interview on the basis of ADAS non-cognitive scale in Urdu.
Results: A total of 100 patients were included (mean age 77 ± 7 years, 65% men). Almost all patients (90%) had BPSD at inclusion, 17% of whom reported psychotic episodes. The most prevalent symptoms were lack of concentration (56%), tremors (56%), depression (44%), lack of cooperation (36%), and delusions (32%). Patients with greater BPSD showed a significantly higher prevalence of psychotic symptoms (delusions, hallucinations, and delirium) and tremors, while emotional symptoms (tearfulness and apathy) predominated in patients with less severe BPSD.
Conclusions: Our study showed that patients with AD have a high prevalence of non-cognitive symptoms. These symptoms vary from the list of symptoms provided by the Alzheimer’s Association.
Alzheimer's disease (AD) is a community health problem that results from ageing (Brookmeyer and Gray, 2000). The main symptoms of dementia are functional, cognitive, and behavioural manifestations. Behavioural symptoms may appear before cognitive alterations (Rubin and Kinscherf, 1989, Petry et al., 1988), and vary according to dementia severity (Irigoyen et al., 2004). Behavioural and psychological symptoms of dementia (BPSD) are non-cognitive symptoms commonly associated with AD. BPSD increase impairment in daily living activities and have to be picked up early for better outcome (Mok et al., 2004, Lyketsos et al., 1997).
Several studies have been conducted to assess the prevalence of BPSD symptoms. Depending on the type of population studied and on the methods used to assess it, the prevalence ranges from 61% to 92% (Swearer et al., 1988). Behavioural disturbances represent the main reason for early institutionalization (Hebert et al., 2001, Steele et al., 1990), increasing the overall financial cost (Fillit and Cummings, 2000). When correctly diagnosed, these disorders can be efficiently treated (Lopez-Pousa et al., 2008, Cummings et al., 2008).
Study design and conduct
A cross-sectional observational study was conducted at the Department of Psychiatry, Services Institute of Medical Sciences and Services hospital, Lahore-Pakistan. The study was approved by the Ethical Committee of the Hospital and written informed consent was taken from all the patients and their carers.
Patients with diagnosis of AD according to DSM-IV criteria were registered for the study. Patients were divided in to two groups. Patients in the first group had semi-structured interviews on ADAS-noncog and had total scores ranging from 26-50. The patients in the second group had scores ≤ 25. The ADAS-Noncog is a validated 10-item tool that examines aspects of mood (tearfulness and depression) and behaviour (lack of concentration, lack of cooperation, delusions, hallucinations, pacing, motor behaviour, tremors, and appetite change). Each item is rated on a 5-point scale; thus, total scores range from 0 to 50. Higher scores represent greater mood or behavioural disturbances. Ratings were made by the examiner based on the information obtained from patients, family members or caregivers, and professional observations.
At the selection visit, in addition to semi-structured interview on ADAS-Noncog test, MMSE test was performed and the presence or absence of BPSD during the last year was recorded.
The main outcome of the study was the ADAS-Noncog score obtained at baseline. The main variable of the study was dementia severity which was categorized into three categories: mild (27-21), moderate (20-11) and severe (≤10) according to MMSE scores.
Secondary variables included demographic data, pharmacological treatments for AD/BPSD in the last year, concomitant diseases and treatments, presence of psychotic symptoms and extra-pyramidal symptoms (tremors, rigidity, hypo-kinesia, postural instability, and fluctuating cognition) during the last year, and the description of the most frequent BPSD at inclusion and during the previous year (possible symptoms included ADAS-Noncog items and some BPSD of the International Psychogeriatric Association (Lyketsos et al., 2002), such as apathy, anxiety, agitation, and delirium.
All statistical analyses were made with the SPSS 12 version software using a t-test and ANOVA. Data are presented as percentages for discrete variables, and as mean ± SD for continuous variables. Differences between groups were assessed using the Chi-square test for categorical data and using one-way ANOVA (or Mann-Whitney test when data was not normally distributed) for continuous variables. The association between continuous variables was tested by using the Spearman correlation coefficient.
A total of 100 patients were included in the study, 46 of them were in the higher BPSD group and the remaining in the lower BPSD group. The mean semi-structured interview score on the basis of ADAS-Noncog score in the higher BPSD group was 29.8 ± 3.7, indicating a moderate degree of behavioural symptoms. Patients in the lower BPSD group showed an average score of 10.4 ± 6.2.
The mean age of the overall sample was 77.2 ± 6.8 years, and 65% were women. Half of the patients (59%) had no primary education, whereas 34% of them completed primary school, 5% secondary education, and 2% had a university degree. Since most patients (85%) were living at their home, the caregiver was usually a family member, especially a son or daughter (54%) or the spouse (39%).
Ninety percent of patients had shown behavioural symptoms during the previous year. The most common were lack of cooperation and depression, with prevalence above 50%. It is noteworthy that these symptoms had been under diagnosed, since only 41% of the studied population had prior diagnosis of BPSD. Likewise, more than half of the patients (54%) had experienced extra-pyramidal symptoms, predominantly tremors (38%) and rigidity (14%). Psychotic symptoms occurred in 17% of patients, with an average of 2.1 ± 2.7 symptoms.
On the basis of the MMSE score, dementia severity was usually mild (49%) to moderate (38%). Only 13% of the patients had severe dementia.
At inclusion time, almost all patients showed some behavioural symptoms (92%). The most prevalent were: lack of concentration (56%), tremors (56%), depression (44%), lack of cooperation (36%), delusions (32%), motor behaviour (29%), and tearfulness (28%).
Among patients in the lower BPSD group, the most prevalent were emotional symptoms such as tearful mood (p = 0.0170) and apathy (p = 0.0310). Regarding dementia severity, there were no significant differences in MMSE score between both groups (p > 0.05).
Correlation between the presence of BPSD and dementia severity
A significant negative association was seen between dementia severity (MMSE score) and BPSD scores (p = 0.028) in patients in the higher BPSD group, indicating that BPSD symptoms got worse when cognition decreased. The behavioural symptoms which showed significant associations with MMSE were lack of cooperation (p = 0.047) and appetite change (p = 0.034).
The results obtained in the present study are consistent with other published studies that demonstrate that lack of concentration, tremors, depression, lack of cooperation, and psychotic symptoms, are frequent in AD patients (Ikeda et al., 2004).
In our study, 90% of the overall population showed at least one BPSD in the previous year, and 92% at the time of evaluation. Another study based on ADAS-Noncog scale (Lyketsos et al., 2001) reported that 97% of all patients had some behavioural symptoms at admission to hospital.
According to our results, the most frequent BPSD was lack of concentration and tremors with prevalence around 56%. Similar results were obtained by Marin and colleagues (1996) when studying non-cognitive disturbances in AD. Concentration alterations and lack of attention appear very early in AD patients (Kim et al., 2007), probably due to the bilateral tempo-parietal degeneration associated with this disease (Louis et al., 1998a). The decrease in concentration is positively correlated with cognitive impairment, suggesting that this symptom should be considered a central deficit in AD. Tremor, in its different manifestations, is common among elderly population aged over 65 (Louis et al., 2000, Louis et al., 1998b). In our study, tremor was one of the behavioural symptoms that differentiated patients with higher and lower BPSD scores.
Among BPSD symptoms, depression is also common in AD patients, and strongly correlates with tearful mood. In our study, depression was in the third position with a prevalence of 44%. These results are in accordance with those obtained in previous studies (Martinez et al., 2008). However, depression rates are variable (Hwang et al., 2004). Although the relationship between dementia and depression is controversial, the latter constitutes an independent risk factor for AD (Troisi et al., 1993). Depressive symptoms are frequent among patients with AD in absence of major depression (Mackenzie et al., 1989). In contrast to our study, other studies did not find correlation between cognitive impairment and depression (Gabryelewicz et al., 2007), showing that the onset of depression might occur at any stage of the disease.
Lack of cooperation, which is generally related to an increase in motor behaviour, may be a result of the normal course of disease. Results in our study show, the lack of cooperation to be less correlated with the degree of cognitive impairment (MMSE score). However, its frequency in our sample (36%) points to its relevance among non-cognitive symptoms.
Pacing is especially annoying to caregivers (Verkaik et al., 2007) and, depending on the population series, its occurrence range from 10% to 60% in AD patients (Burns et al., 1990). The ratio of patients showing increased motor activity or pacing (29% and 24%, respectively) is comparable to the one obtained in other studies (Purandare et al., 2001). Unusual motor behaviour, which can lead to psychomotor agitation is frequent in patients with AD (Purandare et al., 2001), and represents 38% of patients (Copeland et al., 2003). Agitation may indicate a frontal deficit and has a serious impact on caregivers (Salzman, 1988). In our study, agitation was prevalent in 17%.
Although previous studies demonstrate the relationship between delusions and hallucinations and the degree of cognitive impairment (Reisberg et al., 1996), no correlation was found in the present study. Psychotic symptoms of AD, including delusions and hallucinations, significantly characterize those patients in the higher BPSD group, probably because of the increased severity of disease. Both symptoms are predictors of an increased functional and cognitive decline. Moreover, hallucinations have been associated with a higher percentage of institutionalization and mortality (Ferretti et al., 2001). In a cross-sectional study which included patients with AD, vascular dementia, and dementia with Lewy bodies (DLB), the presence of delusions and hallucinations were related to a higher agitation and aggressiveness (Miller et al., 1993). On the other hand, other studies failed to find any significant correlation (Kumar et al., 1988).
Anorexia, increased appetite, and dietary changes are some of the of the appetite disorders occurring in AD (Haider and Shah, 2004). Among behavioural symptoms, appetite change exhibited mild, although significant, negative correlation with dementia severity. However, reduced intake is the most frequent alimentary disturbance in these patients. A previous study (Swearer et al., 1988) demonstrated higher frequency and severity of BSPD in patients with AD who lost weight. Several hypotheses, such as medial temporal cortex atrophy, have been postulated to explain the reduced intake and weight loss observed in these patients (Hebert et al., 2001).
The prevalence of apathy (20%) is similar to that reported in the literature (Lyketsos et al., 2002). Apathy is common among patients with AD, and has an early onset in the course of the disease (Copeland et al., 2003). A comparative study including patients with AD, patients with depression, and healthy subjects, showed that apathy may be found isolated or coexist with depression, but it does not increase depression scores (Mackenzie et al., 1989).
According to various studies, the frequency of anxiety in patients with AD ranges from 40% to 60% (Kim et al., 2007, Haider and Shah, 2004). Anxiety, involves 19% of the studied patients. It predominates during the initial phases of the disease, when patients become aware of their deficit (Kim et al., 2007). However, only 5% to 6% of the affected patients fulfill DSM-IV criteria for generalized anxiety disorder (Mackenzie et al., 1989).
Among behavioural symptoms, appetite disturbances and lack of cooperation showed the highest correlations, whereas a tendency was observed for concentration alterations. The relationship between cognitive impairment and BPSD is controversial. Some studies support a relationship (Reisberg et al., 1996), while others do not (Purandare et al., 2001). Discordances in BPSD prevalence reported by different studies are probably due to the different scales used, as well as to cultural differences (Verkaik et al., 2007).
The present study shows some limitations that should be addressed. First of all, the patients sampled may suffer from more behavioural disturbances than the average population because the study was conducted in an outpatient clinic. Second, the lack of correction for multiple testing is also a limitation of our study.
In conclusion, the present work has several implications for the treatment of AD. The high prevalence of BPSD in patients suffering from AD implies that the assessment of behavioural symptoms is of great importance in clinical practice.
BPSD are often a manifestation of cognitive decline and constitute one of the most common causes of family burden and patient institutionalization. The proper management of these symptoms will therefore increase their wellbeing and quality of life (Copeland et al., 2003).
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