About 23% of people with schizophrenia experience their first episode after the age of 40 1,2. Late-onset schizophrenia (LOS) is a controversial term with regard to both the age of onset (≥40 or ≥50) and etiology and function. Although a recent International Consensus Statement 3 attempted to address inconsistencies in nomenclature and age cutoffs, it could only differentiate between LOS (onset between 40 and 60 years) and very late-onset schizophrenia-like psychosis (onset after 60 years) 4. One of the controversies was whether the cognitive function in LOS was similar to or different from that of early-onset schizophrenia (EOS). Although some studies have reported an association between earlier age at onset and more severe cognitive deficits 5–7, others failed to find differences between the cognitive profiles of individuals with EOS and those with LOS 8–10. Further, the nature of the cognitive deficits that may be associated with age at onset varies in different studies.
Some studies found that individuals with LOS seem to have some relatively preserved cognitive functions such as arithmetic, digit symbol coding, and vocabulary. Further, assessing semantic organization, Paulsen et al.11 reported that individuals with LOS (age at onset >45 years) were preserved compared with individuals with EOS. In contrast, a meta-analysis carried out by Rajji et al.12 reveals that participants with LOS are severely impaired with regard to measures of auditory and visual attention, fluency, global measures of cognition, intelligence quotient, and visuospatial construction, more so than individuals with youth-onset schizophrenia or first-episode schizophrenia for most of these measures. In Egypt, although 6% of the population is aged above 60 years, which expected to reach 11.5% by the year 2025 13, there are few studies on clinical profile, function, and cognitive dysfunction of LOS. Hence, this study tested the hypothesis that LOS had cognitive impairment that differed from that of EOS in pattern and severity. Thus, we aimed to describe the profile of cognitive impairment in LOS and compare it with that in EOS with regard to pattern, severity, and its effect on daily function.
Aim of the study
The aim of this study was to objectively assess cognitive performance and daily functioning in a group of Egyptian patients with LOS, to compare them with those in a group of old healthy individuals, and to compare LOS and EOS as regards cognitive profile and daily function.
Subjects and methods
This is a cross-sectional, comparative study. This study is a part of a larger study that is concerned with different aspects of LOS 14,15. One hundred patients were recruited during a 1-year period from March 2008 to February 2009; they were selected from inpatients and outpatient clinics of Ain Shams University Hospitals (Department of Geriatric Medicine and Institute of Psychiatry and Abbasseya State Hospital). Patients were further divided into two groups according to certain inclusion and exclusion criteria, as mentioned below. The first group consisted of 50 patients who developed schizophrenia above 50 years of age (as defined by the International consensus, age of LOS patients ranged between 40 and 60 years) 3. We chose a cutoff age of 50 on the basis of the age limit at our geriatric clinic. The second group consisted of 50 patients who were above 25 years of age (to avoid adolescence-onset schizophrenia) and developed schizophrenia before 30 years. Both groups were on medication. Patients with a history of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-defined schizophrenia or other psychoses (schizoaffective disorder, paranoid disorder or mood disorder), those with psychotic symptoms secondary to other mental or medical conditions, with substance-induced psychosis, with severe sensory–motor deficit or major organ failure that may affect cognitive function, and those who recently underwent electroconvulsive therapy (within last 3 months), which may affect cognitive function, were excluded. The third group consisted of 50 healthy individuals who were age and sex matched with the old schizophrenic group and were chosen from among relatives of patients who were attended the Department of Geriatric Medicine or the Institute of Psychiatry. This group was compared with the LOS group as regards study variables.
Procedures and tools
After approval of the study by the Ethical and Research Committee of the Institute of Psychiatry, Ain Shams University, patients and/or legal guardians signed a written informed consent form, which explained the full procedure and its aim and stated that participation in the study was voluntary and that participants had the freedom to withdraw from it at any time. After selection of patients and healthy controls and after obtaining their consent, the following assessments were made.
- Clinical assessment.
- Cognitive assessment.
- Assessment of daily function.
Clinical assessment included an introductory interview, preliminary history taking, and clinical examination of all recruited patients and controls. This was followed by physical, neurological, and psychiatric examinations. All patients in the study were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) for verification of the diagnosis. SCID-I is a clinician-administered, semistructured interview that provides a broad coverage of psychiatric diagnoses according to DSM-IV; the Arabic version was used 6. The interview was conducted by expert psychiatrists with good inter-rater reliability (κ≥0.8) 16. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). PANSS 8 was designed to measure the severity of psychopathology in adult patients with schizophrenia, schizoaffective disorder, and other psychotic disorders and emphasizes positive and negative symptom dimensions.
Cognitive assessment included assessment of the intelligence quotient using the Wechsler Adult Intelligence Scale (WAIS). It is a broad assessment tool for cognitive functions. It provides information on the important aspects of an individual’s intellectual function; we used the standardized Arabic version 17. The Cambridge Cognitive Examination Scale (CAMCOG), section B of the Cambridge Mental Disorders of the Elderly Examination (CAMDEX) Scale, was used for diagnosis and measurement of dementia in the elderly. This scale assessed orientation, language (expression, comprehension), memory, recent and remote learning, praxis, attention, abstract thinking, perception, and calculation. We used an Arabic version (back translation correlation coefficient=0.91) 7. The test was conducted by two consultant psychiatrists who were well-versed with the scale and had good inter-rater reliability (κ≥0.86).
Daily functions were assessed using activities of daily living (ADL) and instrumental activities of daily living (IADL) scales 9. There are certain basic abilities that a person must possess to stay at home independently. These abilities allow the person to perform basic self-care tasks, which are referred to as ‘activities of daily living’. ADL are divided into different categories, which include ambulation, bathing, continence of bowel and bladder, dressing, eating, and transfer referring to getting in and out of a chair etc. If an elderly is independent in all ADL, that elderly can function at home without assistance. Early functional loss often occurs in the areas of transportation and housework. IADL evaluates two broad categories: (a) basic self-maintenance behavior such as feeding, dressing, bathing, and mobility and (b) more complex behavior such as managing finances, traveling, and taking medications. These instruments typically consist of nominal or ordinal scales and are fairly easy to administer; we used an Arabic version 10. This test was conducted by two consultant psychiatrists with good inter-rater reliability (κ≥0.82).
All data were recorded, tabulated, and analyzed on SPSS (version 17; SPSS Inc., Chicago, Illinois, USA). Descriptive statistics were obtained as means and SD. Student’s t-test was performed for independent data. Qualitative data were analyzed using Pearson’s χ2-test. P-value was used to indicate level of significance. A P-value less than 0.05 was considered significant.
Clinical and sociodemographic data
In total, women constituted 72% of the late-onset group versus only 36% of the early-onset group. The mean age of the late-onset group was 69.5±3.39 years, whereas that of the early-onset group was 31.42±5.1 years. Further, the mean duration of illness in LOS patients was 12±3.4 years, whereas that in EOS patients was 4.84±1.44 year, as shown in Table 1.
Late-onset schizophrenia versus healthy control
Comparing the LOS group with the group of age-matched and sex-matched healthy controls in terms of cognitive function showed a markedly significant difference as the LOS group had a significantly lower score and more cognitive impairment according to WAIS and CAMCOG. P-values were 0.000 and 0.00, respectively.
At the same time, comparing both groups with regard to daily functioning revealed nonsignificance, as P-values were 0.98 and 0.82, respectively.
Finally, comparing both groups with regard to visual and auditory impairment revealed significant auditory impairment in 30% of LOS patients versus 10% of old healthy controls (P=0.002; Table 1).
Late-onset schizophrenia versus early-onset schizophrenia
Comparing LOS with EOS in terms of sex and sensory deficits revealed a markedly significant difference between both groups (P=0.000); there were higher number of women in the LOS group.
Similarly, there was a markedly significant difference between both groups as regards auditory and visual impairments, which were higher among LOS patients. P-values were 0.000 and 0.000, respectively, as seen in Table 2.
Comparison of daily functioning in both groups using ADL and IADL scales revealed nonsignificance, as the P-value was greater than 0.05. Similarly, comparing both groups in terms of occupation showed no significant difference, as the P-value was 0.615. However, the LOS group had a significantly higher educational level than the EOS group (P-value=0.003; Table 3).
Assessment of psychotic symptoms using the Positive and Negative Syndrome Scale
Patients with LOS had a significantly higher score on the positive scale, whereas a significantly lower score on the negative scale, as well as in terms of psychopathology and total score, compared with patients with EOS, as seen in Table 4.
Using Cambridge Cognitive Examination Scale
Patients with EOS scored better in all items of CAMCOG except for language. Abstract thinking scores were lower in EOS patients than in patients with LOS. In contrast, LOS patients had significantly lower scores on apraxia, perception, and total score (Table 5).
Although EOS patients scored better in all subitems of intelligence quotient, considering the age in calculation of the total score revealed a significantly higher score in the performance test in the late-onset group, as shown in Table 6.
Neurocognition is an important topic in elderly patients because of the growing evidence linking it to everyday functioning 18. Despite notable heterogeneity in the behavioral presentation of schizophrenia, there is general agreement on the presence of neuropsychological impairments that accompany the disorder. However, relatively little is known about the potential interaction between the cognitive deficits associated with schizophrenia and aging 7,18. Hence, cognitive impairment in schizophrenia has been studied extensively in younger patients and is present in most patients, particularly when current performance is compared with estimated premorbid performance 19,20.
In this study, comparing the LOS group with age-matched and sex-matched healthy controls revealed significantly more impairment in the LOS group with regard to cognitive domains, as measured using CAMCOG and WAIS, which proves our hypothesis that the LOS group has significant cognitive impairment. Further, the LOS group had significantly more auditory deficits. Several authors 21,22 have postulated that sensory deficits, particularly hearing loss, may serve as risk factors for late-onset psychosis by reinforcing a pre-existing tendency toward social isolation or withdrawal. However, caution is required when drawing any conclusion from these findings 21,23,24. Comparing both groups with regard to level of functioning revealed no significant difference. This may be explained in terms of both severity and pattern of illness in the LOS patients, as they had less negative symptoms, or may be related to the fact that in our culture, with extended families and many caregivers, old people receive extra care from caregivers.
Cognitive dysfunction in late-onset schizophrenia
Comparing the LOS group with the EOS group revealed that LOS patients were poor performers on measures of cognitive functions (Tables 5 and 6), especially attention, calculation, language, apraxia, abstraction, and perception, as measured using CAMCOG and WAIS, which proves another part of our hypothesis – that is, the LOS group has different patterns compared with the EOS group. This is in concordance with the findings of Rajji et al.12, who stated that the executive functions were consistently impaired in LOS patients. However, the nature of the cognitive deficits that may be associated with age at onset has varied in different studies, as some found no difference in types of cognitive deficits between EOS and LOS patients . Other authors found that LOS is associated with milder cognitive deficits, especially in the areas of learning, abstraction, and cognitive flexibility. Although most studies have suggested a higher-than-normal rate of cognitive decline, some clinical studies reported that psychosis arising late in life is associated with a greater number of cognitive dysfunctions 25.
Similar to previous studies, this study has some contradictions when comparing cognitive functions in the EOS group with those in the LOS group. The EOS group showed significantly better functioning in all items of CAMCOG except language. However, comparing both groups in terms of WAIS showed that despite the EOS group showing better scores in all subitems, on calculating the total and considering the age, we found a significantly better IQ in the LOS group.
Greater impairment in the LOS group may be explained as follows: the duration of illness was longer in the in LOS group (12±3.4) than in the in the EOS group (4.84±1.44) 26,27. The potential impact of chronicity on cognition emphasizes the importance of age at onset and its corollary, duration of illness. Another explanation may be related to effect of age, although comparing our group of LOS patients with another age-matched and sex-matched group revealed that the LOS group was more cognitively impaired; hence, age alone may not have an effect. Another explanation was the auditory and visuosensory impairment, which were more in LOS group. Auditory impairment was also significantly higher in the LOS group compared with age-matched and sex-matched healthy controls. Finally, psychosis late in life may be associated with more cognitive decline, which is in agreement with the findings of Östling et al. 25. In this study, the interaction between duration of illness, aging process, and sensory deficit may lead to more and different cognitive impairments in the LOS group.
Patterns and severity of these cognitive deficits differ from one study to another. There may be a specific pattern of cognitive impairment in LOS patients regardless of the severity and duration of illness, which could explain the contradictory results in this study and in previous studies. This pattern includes impairments in apraxia, abstraction, and perception, as evident in CAMCOG, in addition to impairments in digit span, arithmetic, vocabulary, picture completion, and block design, as evident in WAIS. Another explanation for differences between studies may be different definitions of age of onset in LOS patients, different illness variables, such as duration of illness and severity, and different tools used in the assessment of cognitive function.
In this study, patients with LOS scored significantly lower than patients with EOS on the digit span subscale of WAIS.
These findings are in agreement with those of other studies 20,28–30. Further, the results of the block design test of WAIS (Table 5) are in concordance with those of previous studies showing deficits in visuospatial ability, which indicates that LOS patients performed worse than the EOS patients in the block design test. These results use composite measures of tests thought to assess visuospatial ability 28. Patients with LOS scored lower in items of praxic skills. This conclusion was reached by Schimming and Harvey 31, who found that the patients with schizophrenia performed worse on naming and praxis skills.
In this study, although patients with EOS had a shorter duration of illness, they had more severe symptoms, as evident from the total PANSS score and the negative score, which may affect the pattern of the cognitive deficit. A significantly lower score in the language item of CAMCOG suggested that verbal fluency impairment is a consequence of a disorganized semantic system, similar to the findings of Bowie et al.32. This may be explained by our finding that negative symptoms are significantly higher among patients of the EOS group, as previously reported by Allen and colleagues 33,34, who found that schizophrenia patients with more negative symptoms generate fewer words. Impaired performance on fluency tasks may implicate a dysfunctional semantic system, which has also been suggested as a possible origin of formal thought disorder in EOS 35.
Daily functioning and function in late-onset schizophrenia
With regard to daily functioning in LOS versus EOS patients, despite the fact that the EOS group had more severe symptoms, especially negative symptoms, as evident from PANSS, there was no significant difference between both groups as regards functioning. This may be explained by illness variables, as LOS had a longer duration of illness but less severe symptoms, especially negative symptoms. In addition, although cognitive impairment was more in the LOS group, its pattern differed from that in the EOS group. Another possible explanation was that in our culture responsibilities and duties of older individuals are less, and older individuals receive extra care and support from their caregivers, especially when they are ill, which may compensate for any functional impairment. Hence, no significant difference was noticed between EOS and LOS groups.
At the same time, comparing the LOS group with the EOS group in terms of education and previous occupation (Table 2) revealed that despite more cognitive impairment in the LOS group, they still had a higher education level. This may be related to better premorbid function and delayed age of onset in the LOS group, which may be one of the risk factors and determinants of schizophrenia onset and course, as reported in adolescent-onset schizophrenia 36–38.
Strengths and limitations
This study was one of the few studies in Arab countries that compare cognitive function in an adequately sized sample of EOS and LOS patients using valid and reliable tools such as CAMCOG and WAIS, in addition to assessing several aspects of functioning. Comparing both groups with different durations of illness may act as a possible confounder, as results in the LOS group may be affected by the long duration of illness. Another point was that both groups were not matched regarding sex, as females were more presented among the LOS group, which may be related to the illness itself as previously noticed as females have been noted to exceed males in late-onset psychosis samples by six- to 10-fold 23,39,40. Similarly, Häfner et al. 41 have suggested that estrogens may modulate both the age distribution of onset and symptom severity in women, but not in men. However, our sample was a hospital-based one and may not represent the whole community. Finally, there was no medication control in this study, which may affect the results as well.
Conclusion and clinical implications
Schizophrenia is a heterogeneous disorder. LOS is a subtype of schizophrenia with a certain profile of cognitive dysfunction, which is different from that in EOS. In our study, LOS patients had more cognitive impairment than EOS patients in most of the measured cognitive domains. There was a specific pattern of cognitive deficits in the LOS group, which include immediate memory, visuospatial ability, some of the motor functions (praxia), and executive functions (abstraction and perception), as demonstrated using CAMCOG and WAIS. However, the less pervasive disease process may results in the relative preservation of a particular cognitive function rather than many, such as language, comprehension, digit symbols, total IQ, verbal fluency, and performance. Although LOS constitutes a less severe form of schizophrenia, the pattern of cognitive impairment together with aging may cause similar functional impairments in the EOS group; hence, cognitive rehabilitation and control of other factors that may worsens cognitive impairment, such as medical illness and certain medications (anti-cholinergic, typical antipsychotics, and benzodiazepines), are extremely important.
The authors thank Professor M. El Banouby, former chair of the Department of Geriatric Medicine, Ain Shams University, for his support and guidance. The authors also thank Dr Hisham Sadek, Dr Ahmed El Missiry, Dr Hanan Hussein, Dr Ahmed El Shafie, Dr Mahmoud Tamara, and the other research participants from the Department of Neuropsychiatry, Ain Shams University, for their time, training on tools, guidance, advice, and efforts in completing the study assessment. They would also like to thank Dr Olfat Kahla, senior psychologist in the Geriatric Hospital, Ain Shams University, for her help and Dr Mohamed Hassan Taha from ‘TIT Solution’ for the statistical analysis.
Conflicts of interest
There are no conflicts of interest.
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