Incidence of Alzheimer's disease in India: a 10 years follow-up study.

OBJECTIVE: To determine overall and age-specific incidence rates of Alzheimer's disease (AD) in a southern Indian province, Kerala. MATERIALS AND METHODS: A 10-year (2001-2011) prospective epidemiologic study of community residing subjects aged ≥55 years at enrollment. The catchment area included four urban and semi-urban regions of Trivandrum city in Kerala, India, was selected to provide a range of demographic and socioeconomic representation. Cognitive and functional ability screening were done at baseline and 24-month follow-up assessments. Consensus diagnostic procedures were done using the Diagnostic and Statistical Manual of Mental Disorders, 4 th edition (DSM-IV), and the National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria for the diagnosis of dementia and AD. RESULTS: Among the 1066 eligible participants who were cognitively normal at baseline, 104 developed dementia (98 with AD) over a follow-up period of 8.1 years. The incidence rates per 1000 person-years for AD was 11.67 (95% CI: 10.9-12.4) for those aged ≥55 years and higher for those aged ≥65 years (15.54, 95% CI: 14.6-16.5). In those aged ≥65 years, the world age standardized incidence rate was 21.61 per 100,000, and standardized against the age distribution for the year 2000 U.S. Census, the age-adjusted incidence rate was 9.19 (95% CI: 9.03-9.35) per 1000 person-years. Incidence rate of AD increased significantly and proportionately with increasing age. CONCLUSION: These are the first AD incidence rates to be reported from southern India. The incidence rates appear to be much higher than that reported from rural north India, comparable with that reported from China, and marginally lower than that reported from the western world.

Dementia in Kerala, South India: prevalence and influence of age, education and gender.

BACKGROUND: Data on the prevalence of dementia in India with a large and aging population is scant. We studied prevalence of AD and dementia in Kerala, South India, and effects of age, education and gender on it. METHODS: 2-phase survey on 2466 individuals aged > or = 55 years living in community. Men constituted 41%, < 75 years age in 76.9% and education > or = 4 years in 69.6%. Screening (Phase I) using the instrumental activity of daily living scale for the elderly (IADL-E) and the Addenbrooke's cognition examination (ACE). Diagnostic-assessment (Phase II) was in 532 screen-positives and 247 (10%) screen-negatives. RESULTS: 93 (3.77%) > or = 55 years and 81 (4.86%) > or = 65 years of age had dementia. Age adjusted (against US-population in 2000) dementia (and AD) rates were 4.86% (1.91%) in age > or = 55 years and 6.44% (3.56%) in > or = 65 years. Odds for dementia (and AD) were high with increasing-age 5.89 (15.33) in 75-84, 13.23 (25.92) > or = 85 years, and in women 1.62 (2.95); and low 0.27 (0.16) if education was > or = 9 years. Age and low education increased dementia. Age and female gender increased AD. CONCLUSION: Prevalence of dementia and AD is higher than any reported from the subcontinent suggesting that dementia in Kerala in South India is not uncommon. Increasing age increased dementia and AD. Low-education is associated with dementia and female-gender with AD.

Extent of initial injury determines language lateralization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).

PURPOSE: To assess the prevalence and attributes of atypical language lateralization (ALL) in patients with left mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). METHODS: We recruited consecutive patients with left MTLE-HS, who had undergone resective surgery and had pathologically proven HS. Based on the Wada test, language lateralization was classified into typical (left hemispheric) or atypical (right hemispheric or codominant). We assessed the attributes of patients with ALL using univariate and multivariate analyses. RESULTS: Of 124 patients with left MTLE-HS, 23 (18.5%) had ALL. ALL occurred more frequently in patients with severe initial precipitating injury (IPI), early onset of epilepsy, and a short latent period between IPI and onset of habitual seizures. ALL was more common in patients with bitemporal and extratemporal interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) and extratemporal changes on magnetic resonance imaging (MRI). On multivariate analyses, the age at onset of habitual seizures <6 years, atypical IPI, nonunilateral temporal IEDs, and extratemporal MRI abnormalities independently predicted ALL. The likelihood of ALL was very low ( approximately 1%) when all of these four risk factors were absent, whereas it was very high (>95%), if any three or all four of them were present. CONCLUSIONS: ALL occurs in one-fifth of patients with left MTLE-HS. ALL is more frequent in those with structural or functional extrahippocampal involvement and early onset of epilepsy interrupting the development of normal language networks. Because ALL is uncommon in those with damage/dysfunction restricted to the hippocampus, the hippocampus itself may have only a limited role in determining language lateralization.

Expert Group Meeting on Aphasia: A Report.

A multidisciplinary team of experts took stock of the current state of affairs about many aspects of aphasia in India, including community burden, diagnostic assessment, therapy, rehabilitation, research, education, and advocacy. The broad spectrum of aphasiology was matched by the types of participants ranging from neurologists, speech-language pathologists, clinical psychologists, linguists, to experts in neuroimaging and computer sciences. Threadbare discussion in 16 sessions over 3 days leads to the identification of pressing problems and possible solutions. Many action plans have been envisaged and recommendations made. A few examples with high priority are community-based and hospital-based study incidence and prevalence of aphasia, development of test batteries for the assessment of many components of speech and communication in Indian languages which are validated on rigorous psychometric, and linguistic criteria, national registry for aphasia, educational modules about aphasia for different target groups, resources for advocacy and its training, a bank of research questions and outlines of research protocols for young professionals to pursue. The expert group will continue to oversee execution of some of the actionable plans in short and long term.

Outcome after corpus callosotomy in children with injurious drop attacks and severe mental retardation.

Wide variability in patient selection, extent of callosal section and definition of successful outcome between studies make impact of corpus callosotomy on patients with medically refractory epilepsies difficult to interpret. Severe mental retardation is considered to be predictive of unfavorable seizure outcome after callosotomy. Very little attention has been paid on the influence of callosotomy on the psychosocial burden on the patients' families. We evaluated the seizure outcome, and parental perception about change in cognition and behavior of 17 children (median age 9.5 years, range 3.5-18 years) with severe mental retardation (IQ<30 in all, except one) and injurious drop attacks, who have completed >or=1-year postoperative follow-up after callosotomy. Nearly two-thirds of our patients had >or=90% reduction in drop attacks and generalized tonic-clonic seizures. In the one-stage total callosotomy group, 9 of 11 (82%) patients had favorable outcome, compared to 2 of the 6 (33%) in the partial callosotomy group. Absence of generalized epileptiform discharges on the 1-year postoperative EEG was significantly associated with a favorable seizure outcome. The mean duration of epilepsy prior to callosotomy tended to be shorter among patients with favorable seizure outcome. Postoperative complications were trivial and transient. Nearly three-fourths of the parents appreciated improvements in behavior and attentiveness of their children and were satisfied with the outcome. We conclude that, in children with severe mental retardation and injurious drop attacks, total callosotomy can be undertaken as a one-stage procedure with insignificant morbidity and results in highly favorable seizure outcome.

Mini mental state examination and the Addenbrooke's cognitive examination: effect of education and norms for a multicultural population.

OBJECTIVE: To derive population norms on the Malayalam adaptation of Addenbrooke's Cognitive Examination (M-ACE) and the inclusive Malayalam mini mental state examination (M-MMSE). MATERIALS AND METHODS: Education-stratified norms were obtained on randomly selected cognitively unimpaired community elders (n = 519). RESULTS: Valid data on norms was available on 488 subjects (age 68.5 +/- 7.1 and education 7.9 +/- 5.4). Education and age, but not gender had a significant effect on both M-ACE and M-MMSE. When compared to the effect of age, the effect of education was sevenfold more on the M-ACE and ninefold more on the M-MMSE. The mean composite score on the M-ACE (and the M-MMSE) was 42.8 +/- 9.8 (14.9 +/- 3.1) for those with 0 (n = 72), 55.9 +/- 12.5 (19.7 +/- 4.1) with 1-4 (n = 96), 62.6 +/- 11.4 (21.9 +/- 3.7) with 5-8 (n = 81), 77 +/- 10.2 (25.7 +/- 2.4) with 9-12 (n = 136) and 83.4 +/- 7.2 (26.7 +/- 1.6) with > 12 (n = 103) years of formal education. CONCLUSIONS: Education has the most potent effect on performance on both M-ACE and M-MMSE in the Indian cohort. Education-stratified scores on the M-ACE and the M-MMSE, will provide a more appropriate means of establishing the cognitive status of patients. It is also our feeling that these cut-off scores will be useful across India.

Primary progressive aphasia: a comparative study of progressive nonfluent aphasia and semantic dementia.

Primary progressive aphasia (PPA), a degenerative disorder, is often misdiagnosed as Alzheimer's disease. Its subtypes, semantic dementia (SD), and progressive nonfluent aphasia (PNFA), are often difficult to differentiate from each other. Our objective was to highlight the differences in the language profiles of patients with SD and PNFA. To bring out these differences, we report two patients with PPA, one with SD and the other with PNFA. They were administered the Western aphasia battery (WAB) and a semantic battery, which assesses semantic memory. The profiles of language impairment on the WAB indicated that the patient with PNFA had syntactic errors in expressive speech but relatively preserved semantics and comprehension, whereas the patient with SD had preserved syntax but made semantic errors in expressive speech, and had impaired comprehension. There were differences in their performance on the semantic battery too. The patient with SD made relatively less errors on confrontation naming, although on the pointing task he failed to point to those line drawings, which he was unable to name on confrontation. In contrast, the finding of the PNFA patient was the reverse of this. Supplementing conventional neuropsychological tests with formal tests for assessment of language functions is useful in the early diagnosis of PPA. The performance of PPA patients on a detailed assessment of language that includes use of formal tests such as the semantic battery helps to differentiate PNFA from SD.

Intellectual and language functions in children of mothers with epilepsy.

PURPOSE: To compare the intellectual and language functions of children of mothers with epilepsy (CME) with that of controls matched for age and socioeconomic status. METHODS: Cases were CME, aged six years or more (n = 71), drawn from a prospective cohort in the Kerala Registry of Epilepsy and Pregnancy. Controls were 201 children of parents without epilepsy, matched for age and socioeconomic status. The outcome measures included Indian adaptation of Wechsler Intelligence Scale for children and MLT-a locally developed proficiency test for regional language. All relevant data were abstracted from the registry records. RESULTS: The Full Scale IQ and MLT scores were significantly lower for the cases (87.7 +/- 22.6 and 73.4 +/- 17.3) compared to controls (93.0 +/- 14.4 and 83.2 +/- 11.8). Compared to controls, CME scored poor on all subtests of MLT but their impairment was confined to only some of the subtests of IQ. Maternal education and maternal IQ significantly correlated with low IQ and MLT scores for CME whereas type of epilepsy, seizures during pregnancy or low birth weight did not have any significant association with these outcome measures. Polytherapy and higher dosage of antiepileptic drugs (AEDs) were associated with significant impairment in outcome measures. Infants with low developmental quotient at one year of age continued to have low scores on outcome measures at six years. CONCLUSIONS: Low maternal IQ, maternal education, and antenatal AED exposure were associated with significant impairment of intellectual and language functions for CME at six years.

Instrumental activities of daily living scale for dementia screening in elderly people.

OBJECTIVE: To develop and validate an Instrumental Activities of Daily Living Scale for elderly people (IADL-E) to use in conjunction with cognitive screening tests for dementia in an educationally and socioculturally heterogeneous population. METHOD: Eleven IADL items were selected and weighted for major factors causing heterogeneity in the population--gender, education, social (rural/urban) setting and age. Each item was rated for its applicability (yes/no), degree of disability (scored from 0 to 2) and causative impairment (cognitive and/or physical). From this a composite index of cognitive (CDI) or physical (PDI) disability was derived. Validation was performed retrospectively on 240 subjects: 135 without and 105 with dementia by DSM-IV. RESULTS: The IADL-E had a high internal consistency (alpha = 0.95). The area under the receiver operating characteristic (ROC) curve was 0.97 (CI = 0.94-0.99). A cutoff score of 16 on CDI provided a sensitivity of 0.91, specificity 0.99 and positive predictive value 0.76 (at 5% base rate). IADL-E correlated highly with clinical (DSM-IV, kappa = 0.89), functional (CDR, 0.82) and cognitive (Mini-mental Status Examination, MMSE, 0.74) diagnoses. It showed good responsiveness, with the change on CDI over a median of 23 months correlating significantly with that on MMSE (coefficient = -0.382, CI = -0.667 to -0.098; p=0.009). Individual items had good interrater and test-retest reliability. CONCLUSIONS: The IADL-E is a reliable, sensitive and responsive scale of functional abilities useful in dementia screening in a socioculturally heterogeneous population.

Adaptation of the ACE for a Malayalam speaking population in southern India.

OBJECTIVE: To adapt the Addenbrooke's Cognitive Examination (ACE) as a dementia-screening tool in a community in south India. To establish that items in the adapted version are equivalent to that in the original. METHODS: The ACE was adapted into the local language, Malayalam (m-ACE), following cultural/linguistic modifications. To establish equivalence, qualitative comparisons were made (on the distribution of scores, percentage scoring at ceiling, and relative difficulty across items) between a UK sample receiving the ACE (n = 50; mean age = 67.9 +/- 7.4; education >/= 9, mean = 10.9 +/- 2.5) and a community-based educationally-stratified Indian sample receiving the m-ACE: 'India >/= 9' (n = 50; mean age = 67.8 +/- 5.2; education >/= 9, mean = 13.9 +/- 2.7) and 'India /= 9 groups. Language, Naming, Attention and Orientation are relatively easy (>/= 80% at ceiling) and Recall and Verbal fluency are relatively difficult (