Neuropsychiatric symptoms in mild cognitive impairment: An analysis and its impact on caregiving.

BACKGROUND: Neuropsychiatric impairments play a significant role throughout the course of cognitive decline. Many psychological and behavioral symptoms are present in patients of mild cognitive impairment (MCI) similar to that seen in individuals with dementia. AIMS AND
OBJECTIVES: To study the relevance of neuropsychiatric symptoms of MCI and the impact it has on caregivers of these patients.
MATERIALS AND METHODS: This cross-sectional study was done on 90 patients (30 MCI, 30 dementia and 30 controls) above the age of 50 years. The scales used were Hindi-Mental Status Examination, Global deterioration scale and Neuropsychiatric inventory (NPI). Statistical analysis was done using SPSS 16 software.
RESULTS: 73.33% (22) of the subjects in MCI group, 90% (27) of subjects in dementia group and 53.33% (16) of subjects having normal cognition had neuropsychiatric complaints. 73.33% (22) relatives of subjects in the MCI group, 90% (27) relatives of subjects in dementia group and 46.67% (14) relatives of subjects in the normal group (i.e. control group) experienced some distress. The differences in the mean NPI severity, frequency, distress and total scores of the three groups were statistically significant. Severity and frequency of neuropsychiatric symptoms significantly predicted the caregiver's distress.
CONCLUSIONS: Neuropsychiatric symptoms increase both in frequency and severity with increasing cognitive decline, and they cause distress both to the patient as well as the caregiver; and hence their early recognition is a must. The NPI appears to be a useful tool in that regard.

“Youth lives on hope, old age on memories”

INTRODUCTION

And it is these memories that Alzheimer's disease (AD) gradually washes away. As public awareness of AD is increasing, more people are asking for help and advice about memory problems.[1] With our expanding knowledge of dementia and dementing illnesses it is becoming clearer that the pathological changes in the brain precede the development of clinically evident AD, by many years, perhaps even decades.[2] Hence the field of ageing and dementia is now focusing on the characterization of the earliest stages of cognitive impairment. Research has identified a transitional state between the cognitive changes that occur in normal ageing and AD known as mild cognitive impairment (MCI).[3]

Clinically, MCI can be defined as impairment in one or more cognitive domains-typically memory, or an overall mild decline across all cognitive abilities that is greater than would be expected for individual age or education but insufficient to interfere with social and occupational functioning as is required for a dementia syndrome. The concept of MCI was first described by Peterson in 1997 who described it along a continuum between normal ageing and dementia.[4] The American Academy of Neurology has defined MCI as having memory complaints preferably corroborated by an informant, objective memory impairment, normal general cognitive functioning, intact activities of daily living and not demented.[5] The diagnostic criteria have been now extended to include individuals whose memory complaint is expressed by an informant, individuals with intact memory but significant impairment of a non-memory cognitive function and individuals with some impairment in complex instrumental activities of daily living.[6]

As for dementia, the incidence rates of pre-dementia syndrome appear to increase with age and are higher in subject's with less education.[7] The reported prevalence of pre-dementia syndromes varies between studies as a result of different diagnostic criteria, as well as different sampling and assessment procedures.[8] The rate of development of MCI has been found to be about 5.3% per year (3.5% in the seventh decade of life and 7.2% in the 8th decade).[9] A trend towards higher incidence rates has been reported in men versus women.[10] An Indian study from Calcutta[11] has shown prevalence of MCI to be around 14.89%. However, an incidence of as high as 47.1%[12] and 59%[13] have also been reported in Indian elderly population.

Current interest and studies in pre-dementia syndromes, particularly MCI, reflects the likelihood that MCI is a prodromal phase of dementia, particularly the AD type.[1415] Some clinical studies reported annual conversion rates of MCI to AD between 10% and 15%[1516] whereas others showed rates of up to 40% per year.[10] The Italian longitudinal study on aging reported a progression rate to dementia of 3.8/100 person-years.[17] Petersen and colleagues have hypothesized that multiple domain MCI is likely to progress to vascular dementia, whereas amnestic MCI (aMCI) is likely to progress to Alzheimer's dementia. In a recent clinical study, after a follow-up time of 3 years, 11% of MCI patients showed cognitive improvement, 53% were stable, and 35% deteriorated and were diagnosed with dementia.[18]

Based on cognitive features the various subtypes of MCI are, aMCI and non-amnestic MCI (naMCI) depending on whether there is memory impairment or not; each of which can be further divided into single domain and multiple domain entities based on the number of cognitive domains involved.[19]

Though most of the recent definitions of MCI focus entirely on cognition and usually exclude the psychiatric symptoms, it has been shown that many behavioral and psychological symptoms are present in those with MCI with a similar pattern of occurrence to that seen in individuals with dementia[20] and recently, increasing attention has been paid to the presence and significance of non-cognitive symptoms in MCI.[2021] Global prevalence of Neuropsychiatric symptoms in MCI ranges from 35% to 85% and the most common behavioral symptoms have been found to be depression, anxiety and irritability.[22] Neuropsychiatric impairments play significant roles throughout the course of cognitive decline and it is suggested that they should be taken into consideration even before cognitive impairment is evident[23] as many patients develop neuropsychiatric symptoms as the first indicator of impending dementia.[2425] Psychiatric symptoms have been found to be the first indication of change, before the occurrence of cognitive symptoms, in upto 50% of all dementia patients. More recently, Taragano et al. in their study have proposed four subtypes of patients at risk for dementia: aMCI-which will progress preferentially to AD, multiple domain MCI-may represent either normal ageing process or if progresses may progress either to vascular cognitive impairment or neurodegenerative disorder, single domain naMCI-may progress to frontotemporal dementia, Lewy Body dementia or AD and mild behavioral impairment i.e., MBI-which may progress to frontotemporal dementia, Lewy Body dementia, or AD thereby highlighting the importance of behavioral changes in the elderly as an indicator of disease.[26]

Our study was carried out with the aim of studying the relevance of neuropsychiatric symptoms of MCI and the impact it has on caregiving in these patients.

MATERIALS AND METHODS

A cross-sectional study carried out in geriatric patients and geriatric relatives of other patients in the Psychiatry outpatient department of a tertiary care teaching municipal institute in Mumbai after obtaining requisite approval by the Institutional Ethics committee. Patients and relatives of patients above 50 years of age were included in the study. A total of 90 elderly with 30 each in three groups were taken up for the study, sampling method being consecutive sampling. Group 1 included 30 relatives of patients. These subjects had no cognitive problems. Group 2 had 30 patients fulfilling criteria for diagnosis of MCI according to American Academy of Neurology; and 30 patients fulfilling criteria for diagnosis of dementia, according to Diagnostic and Statistical manual of Mental disorders, Fourth edition, Text revision (DSM IV TR) were included in Group 3.

Patients who at the time of the study had schizophrenia, other psychoses or major affective disorder that clearly preceded the onset of cognitive impairment; current use of alcohol as drug dependence; cognitive impairment considered to be entirely due to use of concomitant medications and severely ill bed ridden patients were excluded from the study.

Written informed consent was taken from the subjects before commencing the study. A semi-structured interview proforma was used to include socio-demographic data, past medical/psychiatric history, medicine use, information regarding clinical features and forgetfulness and treatment taken for the same. A structured clinical interview for diagnosis of MCI according to criteria by American Academy of Neurology was used for group 2. A structured clinical interview was used for DSM IV TR diagnosis of dementia for group 3. The scales used were Hindi–Mental Status Examination (HMSE), Global deterioration scale (GDS) and Neuropsychiatric inventory (NPI).

The HMSE is a cognitive screening scale for rating a subject's overall cognitive performance. Folstein et al. developed Mini-Mental status examination (MMSE) scale in 1975; Ganguli et al. modified MMSE according to Asian standards and formulated HMSE in 1995.[27] The scale consists of a scoring form for rating orientation, memory registration and recall, attention and calculation, language and executive functioning. At the same time, the patient's level of consciousness is also estimated. The scale is used to diagnose MCI and dementia. The cut-off points available are usually same as for MMSE.

GDS, brief cognitive rating scale consists of structured interview for seven points that assesses concentration, recent memory, past memory, orientation, speech, psychomotor abilities, mood and behavior, calculation, feeding concomitants and a functional assessment staging subscale.[28] The GDS is unique in that is permits identification of intellectual deficits without ceiling or flooring effects and is highly sensitive for detection of early changes. It also allows clear identification of a subgroup of patients falling into an intermediate category of MCI associated with ageing. Inter rater reliability for the GDS was found to be high, ranging from 0.87 to 0.97 in various studies.

NPI was developed by J Cummings and Collaborators to assess behavioral problem in geriatric patients.[29] This scale looks at 12 domains of behavioural disturbances: Delusions, hallucinations, depression, agitation/aggression, euphoria, inhibition, irritability, disinhibition, apathy and aberrant motor behavior, anxiety and night time behaviors, appetite/eating. It requires structured clinical interview of patient and primary caretaker. The NPI produces four scores; one for frequency, a second for severity, a third called total which is multiplication of frequency by severity and a fourth for the distress perceived by the caregiver due to symptoms of patients.

RESULTS

Considering the demographic profile of our study sample the mean age in years for subjects in Normal group (i.e. Control group) was 61.50 (SD of 6.45), in MCI group was 63.70 (SD of 7.06) and in the Dementia group, the mean age was 70.03 (SD of 7.20). When this difference was analyzed by using ANOVA the difference in age in the three groups was found to be statistically significant (P:0.000).

The other demographic details of the sample studied are shown in the Table 1.

Table 1

Demographic details of the sample studied

Chi Square tests were used to analyze the demographic variables shown in Table 1 in between the three groups. The differences in sexes (P:0.111), level of education (P:0.135) and marital status (P:0.136) in between the three groups were not found to be statistically significant. The subjects were asked about past psychiatric history recorded or otherwise and it was found that in the entire sample only 6.70% (2) people in the MCI group had past history suggestive of depressive features but were free of symptoms since last two years. When medical illness was considered, 20% (6) subjects of Normal group and 23.30% (7) subjects each of MCI and Dementia group had significant past history of medical illness. Statistically this difference in past psychiatric history (P:0.129) and past history of medical illness (P:0.938) between the three groups was not significant.

The mean HMSE and GDS scores of the three groups is shown in Table 2. The difference in mean HMSE and GDS scores in between the three groups on ANOVA tests was found to be statistically significant (P:0.000).

Table 2

Mean Hindi-mental status examination and global deterioration scale scores of the three groups

NPI was used to assess the neuropsychiatric symptoms. We found that 73.33% (22) of the subjects in the MCI group had some neuropsychiatric complaints. 90% (27) of subjects in dementia group and 53.33% (16) of subjects having normal cognition had neuropsychiatric complaints. The mean NPI severity, frequency, distress and total scores of the three groups are shown in the Table 3. The differences between the three groups in all these NPI domains when analyzed using ANOVA were statistically significant. The frequency, severity and distress scores of various neuropsychiatry symptoms in the MCI group are shown in Table 4.

Table 3

The neuropsychiatric inventory severity, frequency, distress and total scores in the three groups

Table 4

The frequency, severity and caregivers distress scores of various neuropsychiatric symptoms in the mild cognitive impairment group

73.33% (22) relatives of subjects in the MCI group, 90% (27) relatives of subjects in dementia group and 46.67% (14) relatives of subjects in normal group had some distress. On comparison of distress scores in NPI among Normal, MCI and Dementia Groups, the differences on these scores were statistically significant and the magnitude of significance of these scores was more than the significance in NPI total scores. When we further studied the role of frequency and severity of neuropsychiatric symptoms in predicting the caregivers distress on simple regression we found that both severity (Beta: 0.807, P:0.000) and frequency (Beta: 0.860, P:0.000) of neuropsychiatric symptoms significantly predicted the caregivers distress.

DISCUSSION

We found that mean age of subjects increased from Normal to MCI and from MCI to Dementia groups and this difference in age in the three groups was statistically significant suggesting a positive relationship of cognitive decline with age. Panza et al.[17] had found that prevalence of MCI increases with an increase in age, it is 3% in subjects with age 60 years and above, in subjects with age 75 and above prevalence increases to 15%. However, it has been concluded that the exact prevalence of people affected with MCI in certain age is difficult to assess due to use of different criteria, different sampling and different assessment procedures.[30] We found that there was no difference when gender was considered in relation to the cognitive decline in either of the groups suggesting that gender does not play a role in cognitive decline. Whereas in a study done by Gambassi et al., they have reported that prevalence and incidence of AD are higher in women, who also tend to have more severe cognitive impairment.[31] However, nothing much about the difference in genders in MCI is known, until now. The transition from stage of Normal to MCI or MCI to Dementia is however, not affected by sex according to a study done by Kryscio et al.[32] Most of the people in all groups in our study were illiterate or had completed their primary education. Very few among them were graduates. While we found that cognitive decline did not have any relationship with the educational status of the patient other studies have shown that lower education predisposes to AD and MCI. Clark et al. found that education was significantly related to memory performance.[33] Most of the subjects in these three groups were married or widowed. However, the marital status also did not have a significant relationship with the cognitive decline. Extensive studies are, however, not available on this sociodemographic detail.

We found that neither did past history of psychiatric illness nor did history of medical illness play any significant role in any of the three groups, i.e., the cognitive decline was not affected by either of them in our study sample. Patients with past or present history of psychiatric illness in the form of schizophrenia, major depressive disorders and patients taking psychiatric medications are known to be prone to develop some cognitive decline; most of the studies on MCI have, however, kept psychiatric illness in the exclusion criteria.[34] Chronic medical illness has also been known to predispose to cognitive decline. According to studies done by G. B. Frisoni, MCI is associated with poor physical health, leading to the hypothesis of a causal relationship between physical diseases and MCI in older populations whereas our study did not show any such relation.[35] Frisoni et al. have also found that the cognitively impaired elderly without dementia have a greater morbidity/mortality risk hazard ratio of 1.7 with cognitively unimpaired elderly.[36]

NPI was used to assess the neuropsychiatric symptoms. Our study found that neuropsychiatric symptoms were significantly more in frequency as well as severity in MCI group when compared to normal group and dementia subjects had significantly more neuropsychiatric problems than both other groups. These findings show that with the cognitive impairment, the neuropsychiatric problems increase and elderly with MCI do have a significantly higher rate of behavioral and psychiatric problems compared to the normal elderly. In a study by Lyketsos et al. it was found that 80% of dementia participants and 50% of MCI participants exhibited at least one neuropsychiatric symptom from the onset of cognitive symptoms.[20] Certain other studies have reported the presence of neuropsychiatric symptoms from 59%[37] to 86.8%[38] in MCI subjects. It has been shown that prevalence of many neuropsychiatric symptoms increases with increasing severity of cognitive syndromes just as we found that the neuropsychiatric symptoms increased in frequency and severity with the increasing cognitive decline in our study sample.[39] This suggests that neuropsychiatric impairments play a significant role throughout the course of cognitive decline and should be looked for in all patients with cognitive decline. An entity called MBI i.e., mild behavioral impairment has been suggested by Taragano et al. which consists of persistent behavioral changes and mild psychiatric symptoms; non-serious cognitive complaints; normal activities of daily living; and absence of dementia.[40-41] They have found that the MBI group progressed more faster to dementia than the MCI group and that in the MCI group the patients having neuropsychiatric symptoms had a greater risk of conversion to dementia than the MCI group that did not have neuropsychiatric symptoms. However, it may happen that at times it might be difficult to differentiate patients who have psychological symptoms as a consequence of early memory impairment from those in whom cognitive impairment that is secondary to other psychological conditions. As regards dementia even though the diagnosis of dementia is based on the presence of cognitive symptoms,[42] the high prevalence of mood and behavioral disturbances in dementia is well recognized.[20] Much of the morbidity of dementia arises from these symptoms, which increase caregiver depression, diminishes quality of life, exacerbate cognitive and functional impairment, and accelerate institutionalization.[20]

When the neuropsychiatric symptoms in MCI group were studied individually we found that depression and night time behavior were the neuropsychiatric complaints with maximum frequency followed by anxiety, agitation, irritability and apathy. Ellison et al. reported that the most frequently reported neuropsychiatric symptom in their MCI population under study was depression/dysphoria (63.3%), then apathy (60.5%), followed by anxiety, irritability/lability and nighttime behaviors.[38] Low mood has been found to be particularly prominent in the very early stages of cognitive decline.[4344] Also depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia.[25] Detection of depression and its differentiation from apathy in MCI patients is needed because both will require differentiated treatment approaches. Depression has been found to have a complex relationship with cognitive impairment and dementia.[45] It is known that depression is a risk factor for dementia,[46] and depression in MCI has been reported to double the risk of dementia.[4748] Depression is the most commonly studied non-cognitive correlate of MCI and in population-based studies, the estimates of the prevalence of depressive symptoms ranging from 16% to 40% in MCI group.[22] Furthermore, cognitively normal elderly individuals who develop depression are at increased risk for developing subsequent MCI.[49] Van der Linde et al., found that depression was the most common in those with the lowest MMSE scores (17.6%) and more common in MCI (14.5%) than in those with no cognitive impairment (6%)[24] while we found the frequency of depression was more in the MCI group and the frequency was almost double of its presence in the dementia group. The commonest neuropsychiatric problems in dementia group were delusions and night time behavior followed by agitation. Anxiety was the commonest complaint in the normal group followed by agitation. The risk of anxiety was associated with a higher MMSE score similar to the study by Van der Linde et al.[24]

The caregiver's distress was significantly more in caregivers of the dementia group compared to other two groups and in the MCI group, the caregivers were significantly more distressed than the caregivers of the normal group and this distress can be predicted by both frequency and severity of the neuropsychiatric symptoms. These findings show that as in dementia, it is the behavioral problems which give rise to caregivers distress, so too in elderly with MCI it is the neuropsychiatric problems give rise to significant distress in the caregivers. This distress can in turn lead to caregiver burnout and even depression.

CONCLUSIONS

Neuropsychiatric symptoms appear to have an intimate role with cognitive decline. Absence of the same in the normal elderly and an increase in both frequency and severity as one progresses towards MCI and eventually dementia seems to be the trend. This causes distress not only to the patient but also the caregiver.

Therefore, early detection of both neuropsychiatric symptoms and cognitive decline are a must. The NPI seems to be a useful tool in assessment of the same.