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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 1  |  Page : 19-25

Mild cognitive impairment – A hospital-based prospective study


1 Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
2 Department of Clinical Psychology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Date of Web Publication16-Aug-2019

Correspondence Address:
Dr. Shiva Shanker Reddy Mukku
Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru - 560 029, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jgmh.jgmh_30_18

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  Abstract 


Background: Mild cognitive impairment (MCI) is regarded as a transitional state between normal aging and dementia. It may progress to dementia, remain same, or revert to normalcy. Most western studies report an annual conversion of 10%–15% of MCI to dementia. There is a paucity of literature on prospective studies on MCI in India. Objective: The objective is to prospectively study the cognitive status of MCI patients at least 1 year after their diagnosis. The other objective was to find the conversion among the MCI patients to Alzheimer's dementia. Methodology: We followed up persons with MCI above 50 years evaluated in the Geriatric Clinic of National Institute of Mental Health and Neurosciences (NIMHANS) between 2012 and 2014, reassessed their cognitive abilities (neuropsychological measures) 1 year later, and compared them with earlier assessment and the conversion rate among this sample. Hindi Mental Status Examination (HMSE), Everyday Abilities Scale for India (EASI), NIMHANS neuropsychological battery for Indian elderly, and Clinical Dementia Rating (CDR) scale instruments were used for assessment. Results: Twenty-seven persons with a diagnosis of MCI were contacted. Twenty-one participated and underwent repeat clinical and neuropsychological evaluations. The mean duration of follow-up was 1.43 (standard deviation: ± 0.46) years. Six participants (28.6%) had progressed to mild Alzheimer's disease (AD) based on EASI, CDR, and neuropsychological scores, 15 (71.4%) retained their MCI status, and none had reverted back to normal status. The mean age of converters (progressed to mild AD) was 72 ± 5.69 years and nonconverters (remained as MCI) was 72.6 ± 7.16 years. Multiple medical comorbidities were found in both the groups with hypertension being the higher in converters (P = 0.04). Among the converters compared to nonconverters, there was a significant decline in total word list learning (P = 0.006), design construction copy (P = 0.042), total figures canceled in figure cancellation test (P = 0.009), and total omissions on figure cancellation test (P = 0.02). Discussion and Conclusion: Scores on episodic memory, attention, and visuospatial skills were low in the MCI compared to normal controls to start with – there was a further significant decline in few of these parameters over the follow-up. The conversion rate in our study was 28.6% for 1.43 years, which is higher compared to the western studies. Executive function learning and memory were the domains predominantly affected in the converters compared to nonconverters. The study based on tertiary hospital and help seeking with a specialist by those who perceived/were perceived to worsen could be probable reason for this higher rate. Higher medical comorbidities, lower HMSE scores, and executive function and memory at baseline are found to increase the risk of progression to AD.

Keywords: Dementia, elderly, mild cognitive impairment, neuropsychological measures


How to cite this article:
Reddy Mukku SS, Varghese M, Bharath S, Kumar KJ. Mild cognitive impairment – A hospital-based prospective study. J Geriatr Ment Health 2019;6:19-25

How to cite this URL:
Reddy Mukku SS, Varghese M, Bharath S, Kumar KJ. Mild cognitive impairment – A hospital-based prospective study. J Geriatr Ment Health [serial online] 2019 [cited 2019 Sep 16];6:19-25. Available from: http://www.jgmh.org/text.asp?2019/6/1/19/264502




  Introduction Top


There is a gradual but significant increase in elderly population across the world. According to the World Population Aging Report, 2013, the global share of older people (aged 60 years or over) increased from 9.2% in 1990 to 11.7% in 2013 and will continue to grow at the same rate and it estimated to reach 21.1% by 2050. At present, about two-thirds of the world's older persons live in developing countries. It is estimated that by 2050, nearly 8 in 10 of the world's older population will live in the less developed regions.[1] With an increasingly aged population, globally, cognitive impairment is becoming a major public health issue. Cognitive decline is becoming the most feared aspect of growing old because cognitive decline herald's dementia reduces life span. Dementia is associated with carer burden, poor quality of life, and a significant use of the health-care system. According to the Alzheimer's Dementia International latest report, it is estimated that 46.8 million people worldwide are living with dementia in 2015.[2] This number is estimated to double every 20 years, reaching 74.7 million in 2030 and 131.5 million in 2050. India, with over 1.2 billion people, is projected to overtake China in about a decade to become the world's most populous country. In India, older population (above 60 years) is expected to increase from 8% in 2011 to 20% by 2050.[3] As per the India Dementia Report 2010, an estimated 3.7 million Indian people aged over 60 had dementia. It was found that estimated median survival with Alzheimer's disease (AD) was 7.1 years (95% confidence interval [CI]: 6.7–7.5 years).[4]

The term “mild cognitive impairment” (MCI) was introduced in the late 1980s by Reisberg, and since then, individuals with this diagnosis have been extensively investigated from many perspectives including clinical, imaging, genetic, pathological, and epidemiological. The criteria for MCI, as defined by Petersen et al. in 1997, include the following: (1) subjective memory problems, (2) objective memory decline, (3) absence of other cognitive disorders or repercussions on daily life, (4) normal general cognitive function, and (5) absence of dementia.[5] The recent clinical criteria recommended by the National Institute on Aging–Alzheimer's Association for MCI due to AD include (1) concern regarding a change in cognition, (2) impairment in one or more cognitive domains, (3) preservation of independence in functional abilities, and (4) no dementia.[6]

MCI is regarded as a transitional state between normal aging and dementia. In a meta-analysis of 41 cohort studies done to quantify the risk of developing dementia in those with MCI, the cumulative proportion who progressed to dementia, to AD, and to vascular dementia was found to be 39.2%, 33.6%, and 6.2%, respectively, in specialist settings and 21.9%, 28.9%, and 5.2%, respectively, in population studies.[7] A systemic review of 19 longitudinal studies published between 1991 and 2001 that addressed conversion of MCI to dementia found that the rate of conversion was 10% annually.[8] In a prospective study done in Italy to find the rate of progression in 937 MCI participants, it was found that annual rate of conversion was 14%.[9] In the Cache County study the annual rate of conversion in MCI to dementia was 15%.[10] A retrospective cohort study from the French National Alzheimer database of 446,439 patients between January 2009 and January 2014 found annual progression rate to be 13.7% person-years.[11]

The published Indian literature on various aspects of dementia has been on the rise but still far short of the actual need. Very few studies on MCI have been carried out in India. In a community-based study, estimating the prevalence of MCI in Kolkata found prevalence of MCI as 14.89% (95% CI: 12.19–17.95%) and that of multidomain type (8.85%) was higher than amnestic type (6.04%).[12] In the clinic-based study in Mumbai, out of 194 referral cases with cognitive dysfunction, 65.5% of cases had dementia based on clinical, neuropsychological, and imaging evidence and about 22.14% of cases had MCI.[13] In a hospital-based study done in Southern India, where 1190 consecutive patients attending memory clinic were evaluated between 2006 and 2011, it was found that 226 (19.0%) had mild memory complaints. Nearly half of the patients (109 of 226) had MCI according to the modified Petersen criteria. Cerebrovascular disease was found as a common secondary cause.[14] There are quite a few follow-up studies done on MCI in the western countries but very few from India. Since all MCIs do not convert, follow-up studies are needed to know the rate of conversion in the Indian context and to identify any demographic, clinical, biochemical, or neuropsychological profile that would aid in identifying those at higher risk of conversion to dementia so that preventive measures could be initiated at the time of identification of MCI. Based on this background, the current study was planned with an objective to study the cognitive abilities (neuropsychological measures) of the elderly with MCI at least a year later and compare them with the earlier assessments. The other objective was to find the conversion among the MCI patients to Alzheimer's dementia.


  Methodology Top


The study was conducted at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru. Ethical clearance was obtained from the NIMHANS review committee. The participants for the study were persons with MCI based on the Clinical Dementia Rating (CDR) scale and those who had participated in functional MRI and cognitive assessment study earlier between 2012 and 2014.[15],[16],[17] Telephone numbers and other contact details of participants were obtained from the previous study data. A minimum of three attempts were made to contact the participant or primary caregiver of the participant. Postal letters were dispatched wherever proper postal address was available and not reachable via phone. These participants were followed up with at least 1-year interval from the date of previous assessment. For patients who were assessed, consent was obtained from the patient or caregiver if the patient is not in a position to give consent. Sociodemographic details were collected from the participant and the caregiver. Participants also underwent clinical examination and cognitive assessments with the Hindi Mental Status Examination (HMSE), Everyday Abilities Scale for India (EASI), NIMHANS neuropsychological battery for Indian elderly, and CDR scale. Review of investigations and current medication was done.

Instruments

  1. Sociodemographic and course pro forma which included name, age, gender, marital status, education, occupation, income, address, phone number, hospital number, clinical history, family history, vascular risk factors, and medication details
  2. HMSE: This is a modified version of the Mini-Mental Status Examination validated for the illiterate Indian population. This consists of 22 items that test the different components of intellectual capability such as orientation to time and space, attention and concentration, recognition of objects, language function, both comprehensive and expressive speech, motor functioning, and praxis. The cutoff score of ≤23 was taken to screen the dementia cases, with a sensitivity of 88% and specificity of 82%[18]
  3. EASI: This comprises a 12-item brief measure of activities of daily living, with norms, and is appropriate for use in evaluating dementia (together with other tests) among the elderly in India[19]
  4. NIMHANS neuropsychological battery for the elderly: This is a comprehensive and standardized neuropsychological battery, developed for older Indian adults. The tests are described here briefly. Episodic memory was assessed with word list and story recall test assessing immediate and delayed recall. Attention was assessed by digit span test. Constructional ability was assessed with stick construction test. Executive functions were assessed with digit span, Corsi block-tapping test, fluency, and Tower of Hanoi (TOH). Language abilities were assessed by semantic verbal fluency test[20]
  5. CDR scale: This was developed at the Memory and Aging Project at Washington University School of Medicine in 1979. It was developed primarily for use in persons with  Dementia of the Alzheimer type More Details. The CDR is a five-point scale in which CDR-0 connotes no cognitive impairment, and then the remaining four points are for various stages of dementia: CDR-0.5 = very mild dementia, CDR-1 = mild, CDR-2 = moderate, and CDR-3 = severe.[21]


Statistical analysis

Data collected were analyzed using appropriate descriptive statistics such as mean, standard deviation (SD), median, frequency, and percentage to describe the data. We used Wilcoxon signed-rank test for comparison of the continuous variables of paired data in each group. We used Mann–Whitney U-test for comparison of independent sample data. The statistical error was kept at P < 0.05.


  Results Top


There were 27 MCI participants who were contacted via phone and intimated about re-evaluation of their cognitive functions. All these participants had earlier been registered in the geriatric clinical services at NIMHANS. Of those, 15 people came to NIMHANS and gave consent to participate in the study and underwent assessments. Home visits were made for 6 people to complete the assessments. Two participants were seriously ill and they were excluded from the study and 1 participant expired. Two participants declined to participate and 1 was not traceable. The mean duration of follow-up was 1.43 years (SD – 0.46, range – 1.08–2.83 years). In the MCI, of the 21 participants, 6 (28.6%) have progressed to mild AD based on CDR and 15 (71.4%) participants continue in their MCI status and none had reverted back to normal status.

The mean age of the 6 participants who progressed to mild AD was 72 (SD – 5.69) years; among them, 3 were either separated or widowed and 3 were staying with spouse. The mean number of years of formal education was 11 (SD – 4.34). There are medical comorbidities in converters with 6 (100%) having hypertension, 1 (16.7%) diabetes mellitus, 1 (16.7%) past history of cardiovascular event, and 3 (50%) body mass index (BMI) >25 kg/sq. Many participants have multiple medical comorbidities. Out of 6 converters, all have at least one medical comorbidity and 3 have more than two medical comorbidities. Among these, 6 (100%) participants were on antihypertensives, 1 (16.7%) on hypoglycemic drugs, 2 (33.3%) were on antiplatelet drugs, 2 (33.3%) on statins, 3 (50%) on acetylcholinesterase inhibitors, and 1 (16.7%) on psychotropics [Table 1].
Table 1: Demographic and clinical characteristics

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The mean age of the 15 participants who remained as MCI was 72.6 (SD – 7.16) years; among them, 13 (86.7%) were married and staying with spouse and 2 (13.3%) were either widowed or never married. Their mean number of years of education was 14 (SD – 2.83). In the non-converters, 10 patients had at least one medical illness. Among them 7 (46.7%) had hypertension (20%), 3had diabetes mellitus (13.3%), 2 had dyslipidaemia (6.7%), 1 had past history of cardiovascular event (6.7%). They were on multiple medication for physical ailments including antihypertensive 7 (46.7%), hypoglycemic drugs 3 (20%), antiplatelet drugs 4 (26.7%), statins 4 (26.7%), acetylcholinesterase inhibitors 7 (46.7%), and psychotropic drugs 2 (13.3%) [Table 1]. There was a statistically significant difference between two groups in with respect to the presence of hypertension (P = 0.04). There was no statistical difference between the two groups in terms of age, education, gender, marital status, diabetes mellitus, cardiovascular events, BMI, and smoking as shown in [Table 1]. All the MCI patients in the study were given advice on lifestyle modification, physical activity, social engagement, and home-based cognitive activities as part of good clinical practice.

The mean HMSE of converters (6 participants) was 25.3 (SD – 1.51) and EASI was 1.8 (SD – 1.17) at initial assessment. The mean HMSE at follow-up was 21.8 (SD – 2.56), and the decline was found to be statistically significant (P = 0.028). The mean EASI score at follow-up was 3.3 (SD – 2.07), and the change was not found to be statistically significant (P = 0.24) as shown in [Table 2]. The mean HMSE of nonconverters (15 participants) was 28.2 (SD – 1.86) and EASI was 1.3 (SD – 1.53) at initial assessment. The mean HMSE at follow-up was 26.9 (SD – 2.62), and the decline was found to be not statistically significant (P = 0.054) among nonconverters. The mean EASI score at follow-up was 1.6 (SD – 2.17), and the change was not found to be statistically significant (P = 0.27) as shown in [Table 2] even among nonconverters.
Table 2: Hindi Mental Status Examination and Everyday Abilities Scale for India scores at initial and follow-up assessment

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Comparison of neuropsychological measures of converters and nonconverters at baseline shows only subtle differences. There is a statistically significant difference in both the groups in logical memory immediate recall (P = 0.003) and digit span forward (P = 0.04) and digit span backward (P = 0.004), as shown in [Table 3]. Comparison of the baseline and follow-up data of neuropsychological measures of the whole MCI group is shown in [Table 4]. In the 21 participants, means were calculated for all domains of neuropsychological functions at initial assessment and at follow-up. Wilcoxon signed-rank test was carried out to find the significance in the paired data. It was found that as a group, the MCI patients over the follow-up had a significant decline in their cognitive abilities assessed by design construction immediate recall (P = 0.003), categorical verbal fluency (0.001), attention trail commissions (P = 0.011), and total TOH trails completed (P = 0.01). There is no significant decline in certain domains such as total word list learning (P = 0.710), delayed word recall (P = 1.000), 10-word recognition (P = 0.702), immediate logical memory (P = 0.803), delayed logical memory (P = 0.074), design construction copy (P = 0.134), design construction delayed recall (P = 0.190), digit span forward (P = 0.057), digit span backward (P = 0.509), spatial span forward (P = 0.658), spatial span backward (P = 0.236), spatial span backward (P = 0.236), attention trail time (P = 0.339), total cancelled in attention trail (P = 0.679), total moves in TOH (P = 0.110), total time taken for TOH (P = 0.054), and total violations (P = 0.332).
Table 3: The cognitive measures among converters and nonconverters at baseline

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Table 4: All mild cognitive impairment participants with the initial and follow-up data of neuropsychological measures showing change in cognitive measures

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Among the converters and nonconverters at follow-up, there are notable differences in certain domains of neuropsychological measures. There is a significant decline in total word list learning (P = 0.006), design construction copy (P = 0.042), total figures cancelled in attention trail (P = 0.009), and total omissions on figure cancellation test (P = 0.02). The difference which was noticed at baseline on logical memory immediate recall and digit span forward and backward was not present at follow-up, as shown in [Table 5].
Table 5: The difference in cognitive measures among converters and nonconverters at follow-up

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  Discussion Top


The follow-up rate in our study is 77.8% after a mean duration of 1.43 years (SD – 0.46). After the follow-up assessment of the sample, it was found that there was a decline in cognitive status of most participants, some to a significant extent, and few to a lesser extent. In a proportion of participants, there is a change in cognitive status to an extent that there is a need for revision of their diagnosis. The revision of the diagnosis was done using CDR scale. In the MCI of the 21 participants, 6 (28.6%) had progressed to mild AD, 15 (71.4%) participants were stable in their MCI status, and none had reverted back to normal status. In a prospective study done in Italy to find the rate of progression in 937 MCI participants, it was found that annual rate of conversion was 14%.[9] In another study done to find the conversion in Cache County, it was found that annual conversion rate was 15%.[10] A retrospective cohort study conducted from the French National Alzheimer database among 446,439 patients between January 2009 and January 2014 and annual progression rate was found to be 13.7% person-years.[11]

Among the few Indian studies, a prospective study was done in Kolkata where 21 consecutive nondemented, nondepressed individuals from the community above the age of 50 years and those who had memory complaints were followed up annually from 2003 to 2007. In that, 13 (61.9%) cases showed normal cognition throughout the period of follow-up, but the other 8 (38%) manifested cognitive dysfunction. Among the 8 cases, 1 (4.7%) progressed from MCI to AD, 2 (9.5%) cases converted from one MCI subtype to another, 5 (23.8%) cases improved to normalcy, and two cases died during the follow-up.[22] The conversion rate in our study was 28.6% for 1.43 years, which is higher compared to the western studies and also the Kolkata study. Probable reason for higher rate is that the study was done on hospital-based clinical sample and they had higher rate of medical comorbidities. The people in the MCI group who were progressing toward dementia probably had higher follow-up due to perceived worsening and participated in our study.

Neuropsychology has helped us in understanding which functions of the brain are affected during the course of Alzheimer's dementia and in turn elucidating the progression of pathology in the brain. Many studies looked into the neuropsychological changes during the course of AD and how they differ from aged related forgetting. Patients with very early AD are particularly showed impairments on episodic memory manifest as decline in delayed recall.[23] Deficits in executive functions responsible for concurrent mental manipulation of information, concept formation, problem solving, and cue-directed behavior also occur early in the course of AD;[24] this is followed by impairments on tests of confrontation naming, verbal fluency, and semantic categorization.[25],[26] Deficits in attention and visuospatial abilities develop during the latter part of AD.[27] In our study, at the follow-up, there is a significant decline in verbal fluency, design construction immediate recall, commissions in attention trail, and total trails in executive function. In our study, there is no significant decline in delayed word recall and delayed logical memory, which is contrary to the decline seen in AD. The possible explanation for this could be that the low neuropsychological scores of memory and learning at baseline itself and there was no significant change at follow-up [Table 3]. In case of digit span and spatial span, the scores have got slight better at follow-up possibly due to practice effects. Most of the participants consistently showed decline in verbal fluency (categorical), planning, and problem solving.

In the converters compared to nonconverters at baseline, the difference was more in terms of executive function and memory (digit span and logical memory tests). In converters compared to non-converters, there was a significant decline in learning and memory, sustained attention and constructional ability in the neuropsychological assessment at follow-up. Along with above changes in neuropsychological measures, the converters have a higher proportion of patients with widow status, higher BMI, medical comorbidities (hypertension and cardiovascular events), and lower HMSE at baseline compared to nonconverters which are possible predictors of conversion to AD. There was no statistically significant difference between the converters and non-converters except for hypertension. It could possibly be due to small sample size. The medical comorbidities present or detected during our evaluation in these patients were treated or referred to a physician for optimization of medication as part of standard clinical care.


  Conclusion Top


MCI is an important phase before the development of dementia. It is vital to understand MCI with regard to symptoms, course, progression, and neuropsychological measures. This helps in planning interventional studies to prevent or halt the progression of Alzheimer's dementia. Our prospective study reported a higher conversion to Alzheimer' dementia compared to studies from the west. Compared to nonconverters, converters showed a decline in learning and executive function (predominantly). This study helped in understanding the neuropsychological changes in MCI participants over a short period of time of 12–16 months. The lower HMSE score, higher medical comorbidities, and widow status increase the risk for conversion to AD.

Strengths, limitations, and implications

Our study is one of the few hospital-based follow-up studies done on MCI and Alzheimer's dementia. The follow-up rate in the study was >50%. The higher follow-up rate is because active efforts were taken such as telephonic reminders, sending postal letters asking for participation, and home visits in few cases who were unable to come to hospital. This was also one among the very few studies in India which has studied conversion in MCI to Alzheimer's dementia using CDR along with comprehensive evaluation of cognitive functions. There are few limitations in our study. First, our study done on hospital-based clinical sample used active follow-up methods unlike natural follow-up study; therefore, one should be cautious while generalizing these findings. The follow-up duration of sample varied from 1 to 3 years; there was no fixed duration after which follow-up was done. This makes difficult to predict when the progression occurred. We have not assessed the psychological morbidity using any structured assessment in our study. However, we did not found any major psychiatric illness during the usual clinical interview. The implications of our study include necessary adjustment and advise on cognitive training in whom there was conversion. This study showed that the conversion rate in MCI is probably higher in hospital samples in India compared to longitudinal studies done in other countries, which needs further research to ascertain this finding. Our study also emphasizes the importance of comprehensive care for comorbidity and active pharmacological and nonpharmacological intervention for MCI. Thus, our study highlights the importance of having integrated service/clinics for providing comprehensive care.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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[TAG2]
[TAG3]
[TAG4]