Dement Geriatr Cogn Disord 2014;37:113–124

DOI: 10.1159/000354955 © 2013 S. Karger AG, Basel

Accepted: July 16, 2013 1420–8008/14/0372–0113$39.50/0
Published online: October 10, 2013 www.karger.com/dem

Original Research Article

Mild Cognitive Impairment: Clinical

and Imaging Profile in a Memory Clinic
Setting in India
Suvarna Alladi Mekala Shailaja Kandadai Rukmini Mridula
Chowdary Arikaudi Haritha Nallapareddy Kavitha Shujath Ali Khan
Gollahalli Divyaraj Subhash Kaul
Department of Neurology, Nizam’s Institute of Medical Sciences, Hyderabad, India

Key Words
Mild cognitive impairment · Clinical profile · Petersen’s criteria · Revised NIA-AA criteria ·
Diagnosis · India

Abstract
Background: Despite the increasing burden of dementia in developing countries, mild cogni-
tive impairment (MCI) continues to be underexplored. MCI has conventionally been identified
based on clinical profile, but recently, biomarkers suggestive of Alzheimer’s disease pathol-
ogy have been included in the revised National Institute on Aging and the Alzheimer’s Asso-
ciation (NIA-AA) criteria. In this study, we evaluated the profile of MCI in a memory clinic in
India and explored the applicability of the revised NIA-AA criteria in a limited resource setting.
Methods: Consecutive subjects evaluated at the memory clinic for mild memory complaints
were included and underwent clinical and neuropsychological examination as well as standard
brain imaging. A subset of patients was subjected to imaging biomarker studies as a part of
routine clinical practice. Results: Among the 1,190 patients evaluated during the study period,
226 (19.0%) presented with mild memory complaints. Cerebrovascular disease was a common
secondary cause. Nearly half of the patients (109 of 226) had MCI according to the modified
Petersen criteria. All MCI subjects were educated and the majority were male. A total of 12%
of the cohort was classified by imaging biomarkers as having MCI with intermediate likelihood
of AD according to the NIA-AA criteria. Conclusion: In the setting of urban India, MCI is an
emerging problem; therefore, it was feasible to operationalise the revised NIA-AA criteria in
identifying subjects with MCI with intermediate likelihood of AD. © 2013 S. Karger AG, Basel

This work was conducted at the Nizam’s Institute of Medical Sciences, Hyderabad, India.

Suvarna Alladi, DM
Department of Neurology
Nizam’s Institute of Medical Sciences
Panjagutta, Hyderabad 500082 (India)
E-Mail alladisuvarna @ hotmail.com
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Alladi et al.: Mild Cognitive Impairment: Clinical and Imaging Profile in a Memory Clinic
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Introduction

The concept of mild cognitive impairment (MCI) has been proposed to identify an early
but abnormal state of cognitive impairment and is regarded to be a cognitive continuum
between normal aging and early Alzheimer’s disease (AD) [1]. This entity is considered to be
useful in identifying subjects with mild memory complaints who are at a high risk of devel-
oping AD [2–4]. Most of the literature regarding MCI has emerged from developed countries
that have a high level of awareness about cognitive disorders [1–11]. However, there is limited
literature from developing countries about MCI.
The burden of dementia is increasing in India and other developing countries [12], and
it is likely that the preclinical state of MCI is concomitantly increasing. Recent epidemio-
logical and hospital-based studies from India, China, South Korea, Mexico, Nigeria and the
cross-national 10/66 population-based study suggest that MCI is emerging as a problem
in these countries [13–18]. Epidemiological studies conducted in these countries report
the prevalence of MCI to range from 0.6 to 12.7% [13–16]. Furthermore, a study from
Brazil reported an incidence of 13.2 per 1,000 persons per year for MCI [19]. Reasons for
the smaller number of clinic-based studies include a low awareness about cognitive
disorders and few specialised centres available for their diagnosis and management [14,
17, 20].
In the Indian context, the diagnosis of MCI is made further challenging due to the limited
number of culture fair, locally validated neuropsychological tools available for assessment of
mild cognitive problems, a wide heterogeneity in educational and sociocultural backgrounds
that makes it difficult to determine premorbid functioning successfully, and few trained
personnel to identify the subtle deficits encountered in MCI subjects. Due to increasing
numbers of subjects with MCI, determining the clinical and aetiological profile of patients
seeking help from memory clinics is essential to plan and develop meaningful health care
programs [21].
There has been a recent thrust on the role of biomarkers to identify MCI and demarcate
it from normal aging as well as early AD. Various criteria defining MCI using clinical features
and neuropsychological profile have been proposed over the past decade [5–7]. Petersen’s
criteria are most widely used and depend on clinical and neuropsychological features in
defining MCI and its subtypes [1]. Studies have also used measures of functional activities,
such as the Functional Activities Questionnaire (FAQ), to assess Instrumental Activities of
Daily Living (ADL) to aid in the diagnosis of MCI [11]. The criteria for MCI have been recently
revised by the National Institute on Aging and the Alzheimer’s Association (NIA-AA) and
recommend the use of biomarkers to improve the diagnostic confidence in identifying subjects
with mild cognitive complaints whose underlying pathophysiological process could be AD
[8]. Standardization of these biomarkers in detecting preclinical AD among subjects with MCI
is currently an area of active study [9, 10]. However, availability and access to advanced
neuroimaging techniques and studies on CSF biomarker are limited [22]. Therefore, there is
a need to examine the feasibility of operationalising the revised criteria to diagnose MCI in
this setting.
The current hospital-based MCI study was initiated to evaluate and follow-up a cohort of
people with mild memory complaints presenting to a memory clinic in a developing country.
The purpose of this study was to examine the demographic and clinical profile of MCI, and
since a subset of subjects underwent biomarker studies as a part of routine evaluation, we
aimed to assess the applicability of the recently recommended NIA-AA criteria for diagnosing
MCI due to AD in this limited resource setting.
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Alladi et al.: Mild Cognitive Impairment: Clinical and Imaging Profile in a Memory Clinic
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Methods

Consecutive subjects aged 50 years and above, with mild memory disturbances as their primary
complaint and without other significant neurological symptoms, who attended the memory clinic between
January 2006 and March 2011, were included in this study. All participants were prospectively enrolled as
a part of an ongoing longitudinal project that aims to evaluate subjects with cognitive impairment with
detailed demographic, clinical, aetiological, imaging, and follow-up studies. Patients were referred to the
memory clinic by general practitioners and neurologists, and the patient profile is representative of the
pattern seen at a tertiary neurology service in an Indian city. The study was approved by the local Institu-
tional Ethics Committee, and written informed consent was obtained from the patients and their care-
givers.
A detailed demographic and medical history was taken from each patient and attendant, and a complete
general physical and neurological examination was performed by a neurologist. Neuropsychological testing
was conducted by trained psychologists. All subjects had an informant, typically a spouse or one of their
children. Patient age, gender, educational status in years, occupational status as classified by the National
Classification of Occupations – 2004 [23], history of stroke and the presence of vascular risk factors were
recorded for all subjects according to a structured protocol [20]. All participants were evaluated using the
Mini-Mental State Examination (MMSE) [24], Addenbrooke’s Cognitive Examination-Revised (ACE-R),
adapted and translated into Telugu and Hindi [20, 25], and the Clinical Dementia Rating Scale (CDR) [26].
Depression and anxiety were scored using the Hospital Anxiety and Depression Scale (HADS) [27]. A standard
set of screening blood tests, including thyroid function tests and vitamin B12 levels, and brain imaging with
CT scan or MRI were performed in the majority of patients. Subjects with dementia, clinical stroke, significant
head injury, seizures, psychiatric diseases, including depression (clinical judgement or HADS >14), other
neurological or medical disorders that could account for cognitive impairment were excluded. Patients with
mild memory problems as their primary complaint and in whom a definite cause could not be identified were
subjected to further neuropsychological evaluation.

Neuropsychological Testing
Subjects underwent neuropsychological testing according to a structured neuropsychological test
battery to assess a range of cognitive domains including memory, attention/executive function, language
and visuospatial functions. Episodic memory was tested using the Rey Auditory Verbal Learning Test
(RAVLT), and attention/executive function was assessed by the Trail Making Test (TMT A and B). Language
was evaluated with Category and P letter fluency, naming of twelve pictures, comprehension and repetition
of ACE-R to obtain a 26-point language subscore. Visuospatial functions were assessed using a copy of the
Rey-Osterrieth complex figure (ROCF). These tests are sensitive to early deficits in cognitive domains and
are widely used in routine neuropsychological practice. Furthermore, they have been validated in the Indian
context and normative data are available. Control data for the RAVLT and ROCF tests and TMT A and B were
taken from age-, sex- and education-matched normative data from the NIMHANS neuropsychological
battery derived from an urban population aged between 51 and 65 years in Bangalore, India [28]. For
subjects older than 65 years, control data for RAVLT, ROCF and the TMT were obtained from 60 healthy
age-, sex- and education-matched subjects who were volunteers evaluated in the memory clinic. Control
data for ACE-R were derived from 109 age-, sex- and education-matched volunteers evaluated in the clinic.
To assess each individual subject’s performance on each test, we calculated the z-scores. Subjects were
considered to be impaired on a test if their scores were 1.5 SD below the mean for age-, sex- and education-
matched normative data.

Imaging
A CT scan or a 1.5 T MRI of the brain was performed when feasible. The presence of white matter hyper-
intensities, cerebral infarcts and diffuse cerebral atrophy was noted. Only few patients underwent advanced
neuroimaging techniques. These include MRI of the brain for evidence of medial temporal lobe atrophy and
18F-fluorodeoxyglucose (FDG)-PET for bilateral temporal and parietal hypometabolism [29–31]. Medial

temporal lobe atrophy was rated using a visual medial temporal atrophy (MTA) scale based on a T1-weighted
coronal section of the brain. The MTA score ranged from 0 (no atrophy) to 4 (severe atrophy) which took into
account the width of the choroid fissure, the height of the hippocampus, and the width of the temporal horn
[32]. Patients who had medial temporal lobe atrophy with an MTA score of more than 1 were considered
likely to have AD pathology [33]. FDG-PET/CT of the brain was performed using Siemens Biograph 16 with
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Alladi et al.: Mild Cognitive Impairment: Clinical and Imaging Profile in a Memory Clinic
Setting in India

a dose of 10 mci of FDG and image acquisition 45 min after injection. Images were interpreted on Bronson’s
colour scale. Patients were diagnosed as having FDG-PET findings suggestive of AD in the presence of areas
of decreased metabolism involving the temporoparietal cortex bilaterally [34]. Hypometabolism in the
posterior cingulate gyrus and preserved metabolism in the sensorimotor strip, cerebellum and basal ganglia
were considered to be supportive of the AD pattern.

Diagnosis
Based on the above clinical, neuropsychological, neuroimaging and laboratory data, MCI was diagnosed
by a neurologist with experience in evaluating cognitive disorders, according to the modified Petersen
criteria [1] that have been widely used by the majority of previous studies. Subjects fulfilling criteria for MCI
based on Petersen’s criteria, i.e. subjective memory complaints, objective memory loss as determined by
neuropsychological test scores and absence of dementia as indicated by CDR, were interviewed by a clinician
experienced in the diagnosis of dementia.
According to the imaging findings, patients detected to have strategically located infarcts in areas known
to affect cognition were excluded. In addition, subjects with extensive white matter changes (grade 2 and 3)
on Fazekas scale were also excluded because they were considered to have vascular MCI [35]. Following
neuropsychological testing, MCI patients were classified as having amnestic and non-amnestic MCI. Amnestic
MCI patients were further classified into single-domain (memory only) and multi-domain MCI (memory plus
other cognitive domains). Patients with impairment in non-memory domains were separately designated as
non-amnestic MCI. Subjects were termed as having subjective memory impairment (SMI) when they
presented with memory complaints but performed normally on the neuropsychological tests.
We also studied the applicability of the NIA-AA MCI criteria [8] in the same cohort by re-evaluating
clinical details, neuropsychological and brain imaging data. The NIA-AA criteria incorporate evidence from
biomarkers to support the diagnosis of MCI due to AD as a part of a research. Two classes of biomarkers are
identified: CSF Aβ levels and PET imaging of amyloid deposition using specific ligands (PET amyloid imaging)
that are grouped as biomarkers reflecting Aβ deposition. Further biomarkers reflecting downstream neuronal
injury are: CSF tau levels, various structural and functional imaging measures like hippocampal volume or
medial temporal atrophy by volumetric measures or visual rating, rate of brain atrophy on MRI of the brain,
FDG-PET imaging, and SPECT perfusion imaging. Based on evidence from biomarker studies, patients with
MCI are classified as having MCI due to AD at four levels of certainty.
We compared the characteristics of the MCI cohort derived from applying the modified Petersen criteria
and the NIA-AA MCI criteria. In addition, we compared the demographic characteristics and cognitive status
of subjects with MCI and those with AD evaluated in the memory clinic during the same period. Diagnosis of
AD was established by NINDS-ADRDA criteria [36].

Statistics
Subjects who scored less than 1.5 SD (less than 7th percentile on z-scores) of control mean scores were
considered to be abnormal. Group means were compared using independent samples t tests. Differences in
frequency of deficits between groups were analysed using the χ2 test.

Results

Clinical and Cognitive Profile of the Study Cohort

Of the 1,190 patients evaluated in the memory clinic during the study period, 226 (19%)
presented with mild memory problems as their primary complaint. Forty-four were detected
to have an underlying cause that could explain their memory complaints: 15 subjects were
detected to have vascular aetiology, 12 were significantly depressed, 5 had anxiety, 10 had
vitamin B12 deficiency, 1 patient was subsequently detected to have vasculitis of the central
nervous system, and 1 had a frontal lobe tumour. Thirty-one subjects performed normally on
the neuropsychological tests and were categorised as having SMI (tables 1, 2). Forty-two
subjects with mild memory complaints performed normally on the screening cognitive tests,
but sufficient neuropsychological data were not available to classify them more accurately,
and hence they were also excluded (fig. 1a).
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Alladi et al.: Mild Cognitive Impairment: Clinical and Imaging Profile in a Memory Clinic
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Table 1. Demographic details of

the MCI, AD and SMI groups MCI SMI AD
(n = 109) (n = 31) (n = 172)

Age*** 64.7 ± 9.4 59.6 ± 11.1 69.8 ± 9.2

Male gender* 90 (84.1) 22 (71.0) 97 (56.4)
Literates* 109 (100) 29 (93.5) 152 (88.4)
Years of education** 13.8 ± 3.8 13.0 ± 5.5 10.5 ± 5.8
Monolinguals** 25 (22.9) 8 (25.8) 75 (43.6)
Multilinguals** 84 (77.1) 23 (74.2) 97 (66.4)
MMSE*** 27.7 (1.6) 29.5 (0.8) 18.6 (8.2)
ACE-R*** 86.8 (6.4) 93.3 (2.5) 54.2 (25.2)

Values are mean ± SD or n (%). * p < 0.05, MCI vs. AD. ** p < 0.05,
MCI vs. AD, and SMI vs. AD. *** p < 0.0001, MCI vs. SMI, MCI vs. AD, and
AD vs. SMI.

Table 2. Performance of the MCI

and SMI groups on the MCI SMI p value
neuropsychological test battery (n = 109) (n = 321)

MMSE (max. 30) 27.7 (1.6) 29.5 (0.8) <0.0001

ACE-R (max. 100) 86.8 (6.4) 93.3 (2.5) <0.0001
RAVLT-total (max. 75) 32.2 (7.2) 44.6 (3.4) <0.0001
RAVLT-IR (max. 15) 6.1 (2.3) 9.2 (1.8) <0.0001
RAVLT-DR (max. 15) 4.9 (2.6) 9.6 (3.4) <0.0001
ROCF-copy (max. 36) 30.5 (5.4) 34.2 (1.8) <0.0001
ROCF-delayed
recall (max. 36) 11.4 (5.8) 18.8 (5.2) <0.0001
TMT A, s 49.2 (11.4) 34.5 (10.3) <0.0001
TMT B, s 216 (42.8) 134 (33.5) <0.0001
Letter fluency 9.2 (3.1) 11.2 (2.4) 0.001
Category fluency 13.6 (3.8) 16.8 (2.9) <0.0001

Values in parentheses are percentages. IR = Immediate recall; DR =

delayed recall.

Diagnosis of MCI Based on the Modified Petersen Criteria

Based on the modified Petersen criteria, 109 subjects were diagnosed as having MCI, of
whom 84 were diagnosed as having amnestic MCI and 25 were categorised as non-amnestic
MCI. Their ages ranged from 50 to 83 years (mean age 64.7 ± 9.4 SD), and men constituted
84.1% of the study group. All of them had received at least 3 years of formal education, and
the majority (91.0%) had high school education or above. A total of 77.1% were multilingual.
Of the 109 MCI subjects, 43 (39.2%) were still employed, 61 (55.9%) had retired and 5 (5.5%)
were housewives. Among those employed, 2 were (4.6%) senior officials and legislators, 22
(51%) were professionals, 2 (4.6%) were skilled and service workers and 17 (39.8%) were
engaged in an elementary occupation. The mean MMSE score of the 109 MCI patients was
27.7 and the mean ACE-R score was 86.8 (table 1). Of the 84 diagnosed as having amnestic
MCI, 25 (29.8%) had amnestic single domain MCI. Of the 59 who had multi-domain MCI, 16
had impairment of predominantly memory and attention/executive function, 14 had
impairment of language in addition to memory, 5 had early visuospatial involvement in
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Subjects attending
the memory clinic
1,190

Mild memory
complaints
226

Subjective Known aetiology: 44

memory Vascular – 15
complaints excluded excluded Depression – 12
31 B12 def. – 10
Anxiety – 5
CNS vasculitis – 1
Frontal lobe tumour – 1
Insufficient data
42 excluded

MCI based on Petersen‘s

criteria
109

Amnestic MCI Non-amnestic MCI

84 25

Pure Amnestic
amnestic multidomain
single domain 59
25
a

Subjects attending
the memory clinic
1,190

Mild memory
complaints
226

Subjective Known aetiology: 44

memory Vascular – 15
complaints excluded excluded Depression – 12
31 B12 def. – 10
Anxiety – 5
CNS vasculitis – 1
Insufficient data Frontal lobe tumour – 1
42 excluded

FTD-PNFA
2 excluded

MCI due to AD based on

NIA-AA clinical criteria
107

Biomarker not available Biomarker available

86 21
Fig. 1. a MCI diagnosed according
negative
to the modified Petersen criteria. positive
b MCI diagnosed according to the
MCI – core MCI due to AD –
NIA-AA criteria. CNS vasculitis = clinical criteria intermediate likehood
Vasculitis of the central nervous b 94 13
system.
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addition to memory loss and 24 had impairment of memory in association with two or more
cognitive domains. Twenty-five subjects without significant memory impairment were cate-
gorised as non-amnestic MCI: 8 of them had language impairment, 6 had impaired executive
functions and 11 subjects had language impairment associated with executive dysfunction.

Imaging Profile of MCI Subjects

Standard brain imaging was done in 75 MCI subjects: MRI was performed in 56 and CT
of the brain in 19. Thirty-one subjects had normal imaging (MRI-22, CT scan-9), while abnor-
malities were detected in 44. Twenty-one subjects were reported to have diffuse cerebral
atrophy (MRI-15, CT scan-6), 11 had silent lacunar infarcts (MRI-7, CT scan-4), 9 had periven-
tricular lucencies (PVL), 1 had both diffuse cerebral atrophy and PVL, and 2 subjects had both
silent lacunar infarcts and PVL on MRI scans.
Twenty-one of the 109 MCI subjects (19.3%) underwent additional advanced imaging
studies. Indications for performing advanced neuroimaging were clinically driven and
included subjects with a history suggestive of a considerable drop in memory in the recent
period, those who performed in the lowest ranges on episodic memory tests, and those who
expressed a keen desire to be investigated further for better understanding of their risk of
developing AD. None of them fulfilled criteria for AD. All subjects that underwent further
imaging had multi-domain amnestic MCI and their mean MMSE score was 25.7 and their
mean ACE-R score was 76.6. These scores were significantly lower than in the remaining MCI
cohort that did not undergo advanced imaging. MRI of the brain with visual rating of temporal
lobes was done in 8 subjects and in 5 of them temporal lobe atrophy was demonstrated. Two
subjects had an MTA score of 2 and 3 had an MTA score of 3. FDG-PET was performed in 13
subjects, and 8 had typical findings suggestive of AD (61.5%) with bilateral temporal and
parietal hypometabolism. Of the remaining 5 (38.5%) with indeterminate features, 2 had
bilateral medial temporal hypometabolism, 1 had bilateral medial frontal and temporal
metabolism, 1 had bilateral frontal hypometabolism, and 1 had left frontal and bilateral
medial temporal hypometabolism. All of them complained of memory loss, confirmed by
neuropsychological tests, and none of them had any additional clinical features suggestive
of other degenerative diseases such as frontotemporal dementia (FTD) or psychiatric
disease.

Applicability of the NIA-AA Criteria for MCI

By applying NIA-AA criteria for MCI due to AD to the same cohort, 107 subjects were
diagnosed as having clinical and cognitive syndromes of MCI due to AD. A biomarker study
was available in 21 subjects, based on which, 94 (87.9%) fulfilled core clinical criteria for MCI
and 13 (12.1%) met criteria for MCI with intermediate likelihood of AD (fig. 1b). Since CSF Aβ
or PET amyloid imaging were not performed in the cohort, it was not possible to categorise
any of the subjects as having MCI due to AD – high likelihood or MCI – unlikely due to AD.

Modified Petersen’s Criteria versus NIA-AA MCI Criteria ( fig. 1a, b)

All subjects who fulfilled the Petersen criteria for amnestic MCI met NIA-AA criteria for
clinical and cognitive syndromes of MCI due to AD. Of the 25 subjects who were diagnosed as
having non-amnestic MCI, the majority (23 subjects) met NIA-AA criteria for MCI due to AD.
The cognitive profile of non-amnestic subjects was characterised by language impairment
with impaired naming, repetition and fluency, and executive dysfunction, suggestive of FTD-
progressive nonfluent aphasia variant (PNFA). They were excluded from the MCI cohort
because their clinical profile was not consistent with AD. Furthermore, using evidence from
imaging biomarker studies, it was possible to categorise and redirect a subgroup of 13 subjects
within the amnestic MCI cohort as MCI with intermediate likelihood of AD.
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MCI versus AD
During the same period, 172 subjects were diagnosed as having AD in the memory clinic.
Comparison of demographic and clinical features of two groups revealed that all subjects with
MCI (100%) were literate, while 11.6% of dementia patients were illiterate (table 1). The
mean MMSE and mean ACE-R scores were lower in the AD cohort compared to the MCI cohort,
but this is likely to be a reflection of their higher education status, since scores on these tests
are highly dependent on educational level. During the same period, 13 subjects with MCI and
15 patients with early AD underwent FDG-PET for additional diagnostic support. Eight of the
13 subjects with MCI and all AD patients had FDG-PET findings typical of AD pathology.

Discussion

The study describes the clinical profile, cognitive characteristics and brain imaging
findings of individuals presenting with mild memory complaints to a memory clinic in an
Indian city. A significant finding is that a sizable proportion (19%) of subjects attending the
memory clinic in a developing country sought help for mild memory complaints. Among
them, nearly one fifth were detected to have a definite cause for cognitive decline, with cere-
brovascular disease emerging as the most common aetiology. Nearly half of the subjects could
be categorised as having MCI by Petersen’s criteria. The sociodemographic profile of the MCI
cohort evaluated in urban India demonstrated that all participants were educated, approxi-
mately 40% of them were actively employed and that there was a higher proportion of men.
On applying the recently recommended NIA-AA criteria for MCI due to AD on the same cohort,
nearly all subjects fulfilled core clinical criteria for MCI due to AD. Additionally, imaging
biomarker studies performed by FDG-PET and MRI temporal lobe volumetry were available
in one fifth of the cohort, and accordingly, a subset of patients was categorised as MCI with
intermediate likelihood of AD.
In developing countries like India, increasing urbanization, change in lifestyles and a shift
from joint family system to nuclear families is reducing the ‘sociocultural protection’ of
elderly with cognitive problems. This trend is demonstrated by our finding that 19% of
patients in a memory clinic cohort of a university hospital presented with mild memory
complaints. Around 10% of clinic patients were diagnosed as having MCI. This is slightly
lower than frequencies reported in studies from both developed and developing countries. A
total of 22.8% of patients evaluated in a memory clinic in China, 29% from a clinic in Spain
and 37% of patients of a Swedish study were diagnosed as having MCI [14, 37, 38]. Low
awareness continues to be a major factor limiting early diagnosis in India; however, awareness
is improving through public health measures [39] and better access to health care.
Other significant findings in our clinic population were the high frequency (19%) of non-
degenerative causes of mild cognitive problems. One third had vascular aetiology, reflecting
the high prevalence of cardiovascular disease in India [20] and consistent with studies that
have demonstrated the association between vascular disease and cognitive impairment [40].
Vitamin B12 deficiency was an important reversible cause of cognitive dysfunction, a reflection
of the frequent occurrence of vitamin B12 deficiency-related dementia in India [41].
The sociodemographic characteristics of our MCI cohort also provide insights into the
current scenario of cognitive disorders in a clinical setting in India. All MCI subjects were
educated, a finding of significance in background of a high rate of illiteracy (26%) in India
[42]. The absence of illiterates in our MCI cohort probably reflects the lack of awareness about
dementia among the uneducated people. The occupational status of the cohort was quite
heterogeneous. While 60% were retired from work, 40% were still actively employed.
Furthermore, their skill levels were very variable suggesting that mild cognitive complaints
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caused concern regardless of the kind of work they were engaged in. A large proportion
(84%) of the group consisted of male subjects. This finding is consistent with a recent popu-
lation-based study [43], although other reports demonstrate a similar prevalence of MCI in
both sexes [3, 44]. Our findings are likely to be a reflection of the differences in help-seeking
attitudes for health complaints between men and women in India [45].
In the background of a 15% prevalence of MCI in an urban Indian city [13], the number
of subjects (190) detected to have MCI in the populous city of Hyderabad over a period of 5
years is still small and likely to represent only a ‘tip of the iceberg’. There needs to be more
awareness and improved access to specialist services to address the actual problem of
patients with MCI and dementia in India.
The cognitive profile of our MCI cohort is consistent with previous studies [2, 3, 46–48].
A few individuals (13.7%) with memory complaints had only SMI, and nearly a quarter of
subjects were detected to have non-amnestic MCI. The majority of amnestic MCI subjects had
impairment in more than one cognitive domain (70.0%), and pure amnestic MCI was not so
common in concurrence with previous studies [2, 3, 46–49].
The secondary objective of the study was to explore the feasibility of operationalising the
new criteria that incorporate biomarker data in a low resource clinical setting and compare
the older Petersen criteria with the revised NIA-AA criteria. We found a good concordance
between the modified Petersen criteria and the NIA-AA core clinical criteria in our cohort. All
subjects who fulfilled the Petersen criteria for amnestic MCI met NIA-AA core clinical criteria
for MCI due to AD. In addition, the majority of subjects with non-amnestic MCI also fulfilled
NIA-AA criteria for MCI due to AD. The exclusionary features mentioned in the revised criteria
resulted in the redirection of 2 subjects with non-amnestic MCI towards the diagnosis of early
FTD. Both subjects had language and executive function impairment that was consistent with
a diagnosis of early FTD-PNFA and not MCI due to AD.
With increasing evidence that advanced imaging modalities help in supporting the diag-
nosis of AD in the pre-dementia stage, the last few years have witnessed their use in the
clinical evaluation of subjects with MCI even in the Indian context. This practice has given us
an opportunity to evaluate the feasibility of using imaging biomarkers in our clinical setting.
The pattern of biomarker use in the study reflects the current status of availability and acces-
sibility of biomarkers in India. While FDG-PET brain imaging, SPECT perfusion imaging and
assessment of MRI temporal lobe volumes by visual rating are accessible in tertiary referral
units in India, amyloid imaging, voxel-based measures and CSF amyloid and tau biomarkers
are not yet available for clinical use.
In this cohort, only one fifth of MCI subjects underwent imaging biomarker testing.
Among these, a significant proportion (13/21, 62%) had findings that suggested an increased
risk of progression to AD and were characterised as MCI with intermediate likelihood of AD
according to the revised criteria. Based on exclusionary criteria, 2 patients were also redi-
rected from non-amnestic MCI to FTD. Therefore, our findings demonstrate that the NIA-AA
criteria improve upon the diagnosis of MCI made by the older Petersen criteria [30, 33].
Further, FDG-PET imaging findings of hypometabolism in medial temporal and posterior
parietal cortices in patients with MCI due to AD were similar to findings in AD patients,
suggesting that several patients with MCI due to AD may well represent prodromal AD [50].
One limitation of our study is the small number of subjects that underwent biomarker
studies. It would have also been beneficial to study two cohorts: one group of patients diag-
nosed according to Peterson’s criteria and another diagnosed according to NIA-AA criteria in
order to establish whether the addition of biomarker data actually improved upon diagnosis.
Interpretation of imaging biomarker findings was based on a visual rating scale. The subjective
nature of these scales requires the establishment of interrater and intrarater reliability for
accuracy. Long-term follow-up studies with larger numbers of subjects, more detailed infor-
 Dement Geriatr Cogn Disord 2014;37:113–124 122
DOI: 10.1159/000354955 © 2013 S. Karger AG, Basel
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Alladi et al.: Mild Cognitive Impairment: Clinical and Imaging Profile in a Memory Clinic
Setting in India

mation about functional activities in the Indian context and investigations with imaging and
CSF biomarkers are needed to determine the validity of using functional measures and
biomarkers for the reliable diagnosis of preclinical AD.
In conclusion, subjects with mild memory complaints contributed to a significant
proportion of people referred to a memory clinic in a developing country, suggesting that
awareness is increasing as numbers of cases rise in the community. While secondary causes
could be identified in many of these subjects, nearly half of them fulfilled criteria for MCI. The
study also demonstrated that the recently proposed NIA-AA MCI criteria could be operation-
alised in the context of a clinical setting with limited resources.

Disclosure Statement

The authors declare that they have no conflicts of interest to disclose.

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