ADAS-Noncog is a diagnostic tool especially suitable in outpatient clinics because it does not need a special training and its use requires a short time. In fact, its simplicity could be the main reason for the high proportion (68%) of participating physicians who reported willingness to use it in the future.
An additional advantage of ADAS-Noncog Scale lies in the interview-based assessment of the behavioural symptoms. In contrast, other scales exclusively based on patient relatives or caregiver's reports may distort symptoms, which could be objectively analyzed by clinicians.
The results obtained in the present study are consistent with other published investigations which demonstrate that lack of concentration, tremors, depression, lack of cooperation, and psychotic symptoms, are frequent in AD patients [26
In our patient series, 90% of the overall population showed at least one BPSD in the previous year, and 92% at the time of the initial evaluation. Similarly, another study based on ADAS-Noncog scale [28
] reported that 97% of all patients had some behavioural symptoms at admittance.
Acording to our results, the most frequent BPSD was lack of concentration and tremors with prevalence around 56%. Similar results were obtain by Marin and colleagues when studying non-cognitive disturbances in AD [28
]. Concentration alterations and lack of attention appear very early in AD patients [31
], probably due to the bilateral tempo-parietal degeneration associated to this disease [32
]. Aside from its high prevalence, concentration decrease tends to be 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 [33
]. In our work, tremor was one of the behavioural symptoms that best differentiated between patients with higher and lower BPSD scores. In that regard, patients in the higher BPSD group had higher prevalences of delusions, hallucinations and delirium, so they had higher use of neuroleptic drugs and these ones would in turn induce or worsen tremors.
Among BPSD symptoms depression is also common in AD patients, and strongly correlates with tearful mood. In fact, in our study, depression occupied the third position with a prevalence of 44%. These results are in accordance with those obtained in previous studies [28
]. However, depression frequencies are variable [39
]. Although the relationship between dementia and depression is controversial, the latter constitutes an independent risk factor for AD [40
]. Depressive symptoms are frequent among patients with AD in absence of major depression [41
]. Similarly to ours, other studies did not found correlation between cognitive impairment and depression [42
], indicating that the onset of depression might occur at any stage of the disease.
Lack of cooperation, which is generally related to an increased motor behaviour, may be a consequence of the normal course of disease. As for our results, the lack of cooperation is low correlated with the degree of cognitive impairment (MMSE score). However, its prevalence in our sample (36%) points out its relevance among noncognitive symptoms.
The proportion of patients showing increased motor activity or pacing (29% and 24%, respectively) is comparable to the one obtained in other studies [28
]. Pacing is especially annoying to caregivers [44
] and, depending on the population series, its occurrence range from 10% to 60% in AD patients [29
]. Aberrant motor behaviour, which can lead to psychomotor agitation, is frequent in patients with AD [29
], and represents the 38 out of 100 patients [19
]. In our study, agitation reached a prevalence of 17%. Agitation may indicate a frontal affectation and has a deep impact in caregivers [47
Psychotic symptoms of AD, including delusions and hallucinations, significantly contribute to characterize those patients in the higher BPSD group, probably because the increased severity of disease. Although previous studies demonstrate the relationship between delusions and hallucinations and the degree of cognitive impairment [48
], no correlation was found in the present study. Both symptoms are predictors of an increased functional and cognitive decline. Moreover, hallucinations have been associated with a higher percentage of institutionalization and mortality [49
]. 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 [50
]. Conversely, other studies failed to find any significant correlation [19
Among behavioural symptoms, appetite change exhibited mild, although significant, negative correlation with dementia severity. Anorexia, hyperphagia, and dietary changes are some of the of the appetite disorders occurring in AD [5
]. However, hypophagia is the most frequent alimentary disturbance in these patients. A previous study [51
] 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 hypophagia and weight loss observed in these patients [52
The prevalence of apathy (20%) is similar to that reported in the literature [15
]. Apathy is common among patients with AD, and has an early onset in the course of the disease [3
]. 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 [26
Anxiety, involves the 19% of the studied patients. It predominates during the initial phases of the disease, when patients become aware of their deficit [54
]. According to various studies, the frequency of anxiety in patients with AD ranges from 40% to 60%[19
]. However, only 5% to 6% of the affected patients fulfil DSM-IV criteria for generalized anxiety disorder diagnosis [56
In our patient population, a low significant association between dementia severity and total ADAS-Noncog score was found. Thus, according to our results, noncognitive symptoms might occur at any stage of AD and do not necessarily increase with dementia severity. Among behavioural symptoms, appetite disturbances and lack of cooperation showed the highest correlations, whereas a tendency was observed for concentration alterations. The rest of behavioural symptoms alone do not show significant correlations, so they have similar prevalence at any stage of disease. The relationship between cognitive impairment degree and BPSD is controversial, so that several studies supported it [43
], while others do not [58
]. Discordances in BPSD prevalence reported by different studies are probably due to the different scales used, as well as to cultural differences [59
Regarding therapy, first choice treatments among patients with mild to moderate stages of the disease were administered rivastigmine and donepezil, whereas memantine was predominant in patients with severe dementia. The most used neuroleptic agent was risperidone. These data are similar to those provided by a recent study [60
] which analyzed the use of psychoanaleptic drugs in our environment.
According to the data obtained in principal component analisys using the criterion of eigenvalues >1, it is possible to identify three different subsyndromes (hyperactivity, psychosis and affective dimension) in both, the higher and the lower, BPSD populations. Besides, patients with higher BPSD scores show a new subsyndrome, represented by the lack of concentration or cooperation. To the best of our knowledge, this new subsyndrome have been not previously described, and could be identified as an "inattentional syndrome" characterized by the loss of patience, the frustration, and the lack of cooperation induced by deficient attention. The present study also provides an additional evidence for the presence of neuropsychiatric subsyndromes in dementia, which were previously reported by studies using the NPI [61
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 outpatient clinics. Second, the previous use of antidementia and psychotropic agents in our sample could affect the frequency, severity, and total scores of BPSD. Finally, the lack of correction for multiple testing is also a limitation of our study.
The frequency of hallucinations in our study is around 30%,, a percentage somewhat higher than that reported with the NPI in both epidemiological [15
] and clinical populations [18
]. Although this figure only indicates the presence of hallucinations in the last year, it does raise the possibility that there may have been a number of patients with DLB in our study population, particularly since many DLB patients could meet DSM-IV criteria for AD. Then, the exclusive use of DSM-IV criteria should also be adressed as a limitation.
From a qualitative perspective, the present results should be similar to those obtained in other studies in which different evaluation tools are used. In fact, although other tools [19
] probably assess noncognitive symptoms in greater detail, ADAS-Noncog scale include the main behavioural symptoms for assess dementia. Nonetheless, ADAS-Noncog scale has the limitation of being scored by the examiner based upon patient and caregiver interview, and examiner impression. Consequently, the examiner might be overly influenced by his/her snapshot impression of the patient at the time of the visit, which may not be representative of patient's behaviours during typical daily routines.
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. In this regard, the use of scales such as ADAS-Noncog, which provide information from the patient and/or the caregiver in a short period of time, is recommendable in outpatient clinics.
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 [62