Browsing by Author "Verghese, J"

Now showing 1 - 5 of 5
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    Cerebral Small Vessel Disease and Motoric Cognitive Risk Syndrome: Results from the Kerala-Einstein Study
    (JOURNAL OF ALZHEIMERS DISEASE, 2016) Wang, N; Allali, G; Kesavadas, C; Noone, ML; Pradeep, VG; Blumen, HM; Verghese, J
    Background: The contribution of cerebral small vessel disease to cognitive decline, especially in non-Caucasian populations, is not well established. Objective: We examined the relationship between cerebral small vessel disease and motoric cognitive risk syndrome (MCR), a recently described pre-dementia syndrome, in Indian seniors. Methods: 139 participants (mean age 66.6 +/- 5.4 y, 33.1% female) participating in the Kerala-Einstein study in Southern India were examined in a cross-sectional study. The presence of cerebral small vessel disease (lacunar infarcts and cerebral microbleeds (CMB)) and white matter hyperintensities on MRI was ascertained by raters blinded to clinical information. MCR was defined by the presence of cognitive complaints and slow gait in older adults without dementia or mobility disability. Results: Thirty-eight (27.3%) participants met MCR criteria. The overall prevalence of lacunar infarcts and CMB was 49.6% and 9.4%, respectively. Lacunar infarcts in the frontal lobe, but no other brain regions, were associated with MCR even after adjusting for vascular risk factors and presence of white matter hyperintensities (adjusted Odds Ratio (aOR): 4.67, 95% CI: 1.69-12.94). Frontal lacunar infarcts were associated with slow gait (aOR: 3.98, 95% CI: 1.46-10.79) and poor performance on memory test (beta : -1.24, 95% CI: -2.42 to -0.05), but not with cognitive complaints or non-memory tests. No association of CMB was found with MCR, individual MCR criterion or cognitive tests. Conclusions: Frontal lacunar infarcts are associated with MCR in Indian seniors, perhaps, by contributing to slow gait and poor memory function.
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    Incidence of Alzheimer's disease in India: A 10 years follow-up study
    (Neurol India, 2012-12) Mathuranath, PS; George, A; Ranjith, N; Justus, S; Kumar, MS; Menon, R; Sarma, PS; Verghese, J
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    Interaction with the MAPT H1H1 Genotype Increases Dementia Risk in APOE epsilon 4 Carriers in a Population of Southern India
    (DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2016) Jairani, PS; Aswathy, PM; Gopala, S; Verghese, J; Mathuranath, PS
    Background: This study delineates the role of the interaction of apolipoprotein E (APOE) and MAPT alleles in contributing to disease risks of dementia in a southern Indian population. Methods: A sample of 419 patients comprising Alzheimer's disease (AD; n = 156), mild cognitive impairment (MCI; n = 87), frontotemporal dementia (FTD; n = 127), vascular dementia (VD; n = 37), and dementia with Lewy bodies (DLB; n = 12) was analysed in comparison with a control group (n = 138). APOE genotyping and MAPT haplotyping were performed on all study subjects. Results: Multivariate logistic regression analysis showed that variability on the APOE locus influenced the relative risk of dementia in the study population. The APOE e4 allele increased the disease risk most significantly for AD (OR = 3.468, p < 0.0001) and MCI (OR = 2.901, p < 0.0001). The APOE epsilon 2 allele remained protective for AD (OR = 0.205, p < 0.05). For FTD, VD, and DLB, the APOE epsilon 4 allele was ineffectual in modulating disease risk. The MAPT H1 haplotype was not an overrepresented marker of neurodegenerative diseases. The H1H1 genotype had an additive effect in contributing to either disease risk in combination with the APOE epsilon 4 allele or protection in combination with the APOE epsilon 2 or epsilon 3 allele. Conclusions: This study is a reappraisal of the strong association of APOE variability with AD in southern India when compared to other dementia groups, while the transcriptional differences between MAPT haplotypes have a limited role in Indian dementia patients. (C) 2016 S. Karger AG, Basel
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    Microtubule-associated protein tau genetic variations are uncommon cause of frontotemporal dementia in south India
    (NEUROBIOLOGY OF AGING, 2014) Aswathy, PM; Jairani, PS; Verghese, J; Gopala, S; Mathuranath, PS
    Microtubule-associated protein tau (MAPT) positive neuropathology is the characteristic feature of majority of frontotemporal dementia (FTD) cases, which is due to the mutations or haplotypic variations in the gene encoding MAPT (MAPT). The present study was aimed at determining the frequency of genetic variations in MAPT in a south Indian FTD cohort. The frequency of mutations were determined in 116 FTD, 8 progressive supranuclear palsy (PSP) and 3 corticobasal syndrome (CBS) patients and haplotype diversity were analyzed in a study cohort comprising 116 FTD, 8 PSP, 3 CBS, 194 other dementia groups, 78 mild cognitive impairment (MCI) and 130 cognitively normal individuals and report no pathogenic mutations in FTD/PSP/CBS or haplotypic association with disease risk in FTD or other dementia patients. These findings suggest that there may be other genetic or epigenetic factors contributing to the pathogenesis of FTD in the south Indian population. (C) 2014 Published by Elsevier Inc.
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    Progranulin mutation analysis: Identification of one novel mutation in exon 12 associated with frontotemporal dementia
    (NEUROBIOLOGY OF AGING, 2016) Aswathy, PM; Jairani, PS; Raghavan, SK; Verghese, J; Gopala, S; Srinivas, P; Mathuranath, PS
    Progranulin (PGRN) mutations account for an average of 15% of familial frontotemporal dementia (FTD) cases and 20% of total FTD cases worldwide. Here, we investigated the frequency of PGRN mutations in FTD patients (n = 116) from a clinical cohort of south India and detected one novel mutation located on exon 12 in a familial behavioral variant FTD patient (accounting for similar to 1% of total FTD cases and 6% of familial FTD cases). This mutation was found to introduce a premature termination codon and the prematurely terminated messenger RNA may probably undergo nonsense-mediated decay. In enzyme-linked immunosorbent assay, the proband showed significantly reduced level of plasma PGRN (28 ng/mL) compared with controls (150 +/- 38 ng/mL), which implicates haploinsufficiency as the pathogenic mechanism. (C) 2016 Elsevier Inc. All rights reserved.