Characteristics of behavioral and psychological symptoms of dementia in untreated oldest old Alzheimer's disease*
The contents of this paper were presented previously at the 16th Congress of the American Association for Geriatric Psychiatry in Hawaii, USA, in March 2003 and at the 20th International Conference on Alzheimer's Disease in Kyoto, Japan, in October 2004.
Dr Atsushi Hamuro MD, PhD, Department of Psychiatry, Amekudai Hospital, 1123 Ameku Naha, Okinawa 900-0005, Japan. Email: email@example.com
Background: The proportion of the population aged 85 years and older has increased rapidly in Japan, reaching 2.5 million (1.99%) in 2002. Under these circumstances, the number of dementia patients increases annually. However, few studies have focused on Alzheimer's disease (AD) with an age at onset older than 85 years (oldest old AD). The aims of the present study were to determine the prevalence of the behavioral and psychological symptoms of dementia (BPSD) in patients with oldest old AD compared with those with young old AD.
Methods: Fifty-eight untreated AD patients were divided into two groups: young old AD patients (age at onset between 65 and 70 years; n = 28) and oldest old AD patients (age at onset 85 years or older; n = 30). Then, BPSD were compared between the two groups.
Results: There were significant differences in the frequencies of hallucinations (χ2 = 7.43; P = 0.011) and delusional misidentification syndrome (DMS; χ2 = 7.26; P = 0.011) between the two groups.
Conclusions: The results of the present study suggest that aging may play a part in the occurrence of hallucinations and DMS in oldest old AD patients.
The life expectancy of Japanese people is currently the longest in the world, with an average life span of 78.56 years for men and 85.52 years for women. In Japan, the proportion of the population aged 85 years and older has increased rapidly, reaching 2.5 million (1.99%) in 2002. Under these circumstances, the number of dementia patients increases annually.1 There are some studies investigating differences between early (before age 65 years) and late-onset (after age 65 years) Alzheimer's disease (AD).2,3 However, few studies have focused on AD patients in whom the age at onset is older than 85 years (oldest old AD).4,5
The aims of the present study were to compare the prevalence of behavioral and psychological symptoms of dementia (BPSD) between young old (age at onset between 65 and 70 years) and oldest old AD patients to clarify the clinical characteristics of oldest old AD.6 To eliminate drug-induced BPSD, AD patients with a history of psychotropic drug use were excluded from the study. Therefore, the subjects recruited to the study were untreated AD patients.
We accordingly hypothesized that there are significant differences in BPSD between young old AD patients and oldest old AD patients.
Of the 574 patients who visited the outpatient clinic of the Department of Psychiatry, Yokufukai Geriatric Hospital and Showa University Northern Yokohama Hospital from June 1998 to August 2002, 58 patients were consecutively enrolled in the present study. These patients were diagnosed as having ‘probable AD’ on the basis of the National Institute for Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)7 criteria. The age at onset was between 65 and 70 years or 85 years and older. To avoid bias in evaluating symptoms due to the progression of the disease, the enrollees were limited to patients with AD at the mild and moderate stages (within 6 years from the onset and a Mini-Mental State Examination (MMSE)8 score of 10–24). The exclusion criteria were as follows: probable AD with an age at onset between 71 and 84 years (n = 94); an MMSE score below 10 (n = 50); possible AD (n = 22) according to NINCDS-ADRDA criteria; vascular dementia (n = 68); dementia with Lewy bodies (n = 17); frontotemporal dementia (n = 10); alcoholic dementia (n = 4); other types of dementia (n = 79); age-associated cognitive decline9 (n = 20); delirium (n = 4); delusional disorder (n = 20); mood disorder (n = 32); and a history of psychotropic drug use (n = 96).
The remaining 58 patients were divided into two groups: young old patients (age at onset between 65 and 70 years; n = 28) and oldest old patients (age at onset 85 years or older; n = 30). Cognitive function was evaluated using the MMSE and Clinical Dementia Rating (CDR).10 Psychiatric symptoms were evaluated on the basis of the presence or absence of hallucinations, delusions, delusional misidentification syndrome (DMS) and depression. Behavioral disturbances were evaluated on the basis of the presence or absence of violence, wandering, adverse sleep, pica and hyperphagia. According to the definitions used by Burns et al.11 and Christodoulou,12 DMS includes the following features: (i) ‘phantom boarder syndrome’, consisting of the belief that other (non-existent) people are living in the house, and presenting with a marked paranoid component (e.g. preparing meals for these other people); (ii) Capgras syndrome; (iii) Fregoli syndrome; and (iv) mirror sign. The BPSD components studied were present in the subjects in the previous 4 weeks. The severity of BPSD was measured in terms of the degree of the need for some oral medication. Patients were evaluated (including diagnosis, the age at onset, MMSE, CDR and BPSD) by three psychiatrists, one neurologist and one psychologist.
The safeguards, protocols and acquisition of informed consent of the present study were approved by the Yokufukai Geriatric Hospital Ethics Committee. Statistical analysis was performed using the Mann–Whitney U-test for continuous variables and the Chi-squared test and Fisher's exact test for categorical variables. The SPSS Version 11 for Windows (SPSS, Chicago, IL, USA) was used for all statistical analyses.
The demographic characteristics of the subjects in each group are given in Table 1. With regard to gender distribution, each group had a greater proportion of women. As anticipated, because the subjects were selected to be at similar stages of disease progression, the duration of the disease and the total points in MMSE and CDR were not significantly different between the two groups.
Table 1. Demographic characteristics of the 58 study subjects
|Age (years)||71.29 ± 1.88||89.70 ± 2.45||<0.001|
|Age at onset (years)||68.07 ± 1.80||86.87 ± 2.37||<0.001|
|Duration (years)||3.21 ± 1.13||2.87 ± 1.87||0.393|
|MMSE||17.39 ± 4.26||17.43 ± 3.78||0.970|
|CDR||1.43 ± 0.57||1.60 ± 0.56||0.285|
The frequency of BPSD in the two groups is presented in Table 2. Hallucinations were not observed in the young old patients, whereas delusions and DMS were observed in at least 30% of the oldest old patients. Chi-squared test and Fisher's exact test demonstrated significant differences in the frequencies of hallucinations (χ2 = 7.43, P = 0.011) and DMS (χ2 = 7.26, P = 0.011) between the two groups. With respect to behavioral disturbances, although adverse sleep, pica and hyperphagia were not found in the young old patients, there was no significant difference in behavioral symptoms between the two groups.
Table 2. Characteristics measured using behavioral and psychological symptoms of dementia
|Hallucinations||0 (0%)||7 (23.33%)||0.011||12.07|
|Delusion||5 (17.86%)||11 (36.67%)||0.109||27.59|
|DMS||2 (7.14%)||11 (36.67%)||0.011||22.41|
|Depressive mood||5 (17.86%)||5 (16.67%)||0.905||17.24|
|Violence||2 (7.14%)||4 (13.33%)||0.671||10.34|
|Wandering||8 (26.57%)||9 (30.00%)||0.905||29.31|
|Adverse sleep||0 (0%)||3 (10.00%)||0.238||5.17|
|Pica||0 (0%)||1 (3.33%)||0.330||1.72|
|Hyperphagia||0 (0%)||5 (16.67%)||0.053||8.62|
The present findings indicate significant differences in the frequencies of hallucinations and DMS between young old and oldest old AD patients. This partially supports our hypothesis that there are significant differences in BPSD between the oldest old AD patients and young old AD patients.
When comparing groups of different ages, factors such as gender, type of dementia and degree of cognitive impairment are potential sources of bias.13 Therefore, in the present study, we aimed to decrease bias by comparing two groups with very similar gender ratios, the same disease and the same degree of cognitive impairment.
In addition, patients with AD at the severe stage were excluded from the study (MMSE score of less than 10) because of the difficulty in detecting psychiatric symptoms owing to decreased verbal production for communication14 and this is thought to be a factor influencing the prevalence of BPSD. Moreover, only untreated AD patients were recruited to the present study to eliminate drug-induced BPSD because drugs used to treat BPSD apparently influence the prevalence of BPSD. Mcshane et al.15 reported that neuroleptic drugs may substantially accelerate cognitive decline: patients with AD treated with neuroleptics experienced twice the rate of decline of those who were not treated with neuroleptics and this increased rate of decline was associated with aggression and persecutory ideation. However, the limitations of the present study included a small sample (with associated statistical problems) and the lack of assessment of other factors (including comorbidity, family history and education) that appear to be influenced by BPSD.
Characteristics of BPSD in untreated oldest old AD patients
In previous studies of the clinical characteristics of AD, confusion, anxiety and multiple behavior disturbances have been found more frequently in oldest old AD patients than in young old AD patients.16 However, the characteristics of BPSD in untreated oldest old AD patients have not been completely elucidated. In the present study, the prevalence of hallucinations and DMS in the untreated oldest old AD patients was significantly higher than that in the untreated young old AD patients.
What are the factors responsible for hallucinations and DMS? What are the features of brain function in oldest old AD patients? Most previous AD studies indicate that normal aging is accompanied by a decrease in perfusion in the frontal lobe.17–19 Taking age-related changes in the frontal lobe into account, in previous studies patients with DMS exhibited an increased electroencephalography delta-power in the right hemisphere20 and a significant hypometabolism in the paralimbic and left medial temporal areas.21 In contrast, patients with hallucinations demonstrate diminished regional cerebral blood flow in the right parietal and left medial temporal lobes22 and hypoperfusion in the parietal lobe.23 With respect to the features of cerebral function in oldest old AD patients, researchers have observed a regional glucose metabolic deficit in the paralimbic area and hippocampal formation24 and numerous neurofibrillary tangles within the inferior temporal cortex.25 However, the areas responsible for BPSD and the features of cerebral function in oldest old AD patients have not yet been elucidated completely.
In a preliminary study, comparison of single photon emission computed tomography (SPECT) findings demonstrated a significant decrease in perfusion in the bilateral parietal lobes and left occipital lobe in oldest old AD patients compared with young old AD patients.26 Taken together with the present findings, these results raise the possibility that the low perfusion in these areas in oldest old AD patients is related to the expression of hallucinations and DMS.
The results of the present study suggest that aging may play a part in the occurrence of hallucinations and DMS in oldest old AD patients.
The authors thank Shungyoku Ryo (Department of Public Health, Juntendo University School of Medicine, Tokyo, Japan) for help with data collection and statistical analysis in the present study.