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Mary Ganguli

Publications and source records attributed to Mary Ganguli.

30 records · Page 2Linked to original sources
PubMed2003

Tracking cognitive functioning over time: ten-year longitudinal data from a community-based study.

Over 10 years, a community-based sample age 65> or = years, with a starting cohort size of 1,206, was assessed biennially with the Mini-Mental State Exam; the Consortium to Establish a Registry for Alzheimer's Disease battery; Immediate and Delayed Recall of a Story; Verbal Fluency for P and S, Fruits and Animals; Clock Drawing; Temporal Orientation; and Trail Making tests. We report distributions of scores over time, at each wave, in (a) all individuals who were assessed at that wave, whether or not they participated in all waves, and (b) the Survivor subgroup of 425 participants who completed all tests at all 5 waves. Scores and factor structures remained remarkably stable over the study period. The most marked decline over time was seen on the Trail Making tests. As the survivors are de facto a largely healthy and motivated group, their data can be considered population-based healthy norms and may serve as a reference for other studies conducting repeated evaluations using the same tests.

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PubMed2002

Genetic variation in alpha(1)-antichymotrypsin and its association with Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by extracellular neuritic plaques and intracellular neurofibrillary tangles in brain parenchyma. Alpha-1-antichymotrypsin (ACT) is a component of plaque cores, can bind to Abeta, and has been proposed as a possible candidate gene for AD susceptibility. The genetic association between the ACT codon -17*A allele of the signal peptide polymorphism and AD has been shown in some, but not in all studies. One hypothesis is that the ACT codon -17*A allele is in linkage disequilibrium with unknown functional mutation(s) in the ACT gene. This study was undertaken to identify new mutation(s) in the ACT gene by PCR-SSCP-sequencing and, in conjunction with known mutations, to assess their role in affecting the risk of AD. A total of seven new point mutations were observed: 5'UTR(A-->G), Asp128Asn(G-->A), Ser250Ser(C-->T), Leu301Pro(T-->C), Thr324Thr(A-->G), G-->A in intron 4, and 3'UTR C-->A. Of these, mutations at codon 250, codon 324, intron 4 and 3'UTR showed a frequency of 1% or more. Of the known mutations, Thr-17Ala(A-->G), Lys76Lys(A-->G) and Leu241Leu(G-->A) occur at a polymorphic level. The ACT codon -17*A allele was associated with increased risk of AD (OR for AA vs TT: 1.71; 95% CI: 1.16-2.53; P=0.007), especially in the presence of the APOE*4 allele (OR for AA vs TT: 2.35; 95% CI: 1.13-4.85; P=0.02). The codon 241*A allele and the codon 250*T allele were associated with protective effects against AD (OR: 0.36; 95% CI: 0.13-0.86; P=0.02) (OR:0.39; 95% CI: 0.18-0.85; P=0.02). irrespective of the APOE*4 status. The codon 324*G allele was associated with a marginal protective effect (OR:0.57; 95% CI: 0.26-1.26; P=0.17). While the codon 241*A allele was in linkage disequilibrium with the codon -17*A allele, the codon 250*T and codon 324*G alleles were non-randomly associated with the codon -17*T allele. In contrast, the codon 76*G (OR:1.34; 95% CI: 0.92-1.95; P=0.13), codon 227*G (OR:3.96; 95% CI: 0.83-18.8; P=0.08) and intron 4*G (OR:1.47; 95% CI: 0.88-2.29; P=0.15) alleles were associated with a modest risk of AD, and all were in linkage disequilibrium with the codon -17*A allele. EH-based haplotype analysis showed that certain haplotypes are associated with either higher or lower risk of AD. Our data indicate that the ACT gene harbors several potentially important variable sites, which are associated with either an increased or decreased risk of AD. The non-random combination of risk and protective alleles may explain, in part, why the association studies regarding the ACT codon -17*A have been inconsistent, especially if the frequency of other ACT mutations varies between populations.

3' Untranslated Regions↗
PubMed2002

Rates and predictors of mortality in an aging, rural, community-based cohort: the role of depression.

CONTEXT: Depression, functional disability, cognitive impairment, and self-rated health all predict mortality in the elderly population. There is no consensus on their relative contributions when examined together. OBJECTIVES: To measure rates and identify predictors of mortality in an aging community-based cohort. DESIGN: Ten-year prospective epidemiological study. Predictor variables examined in Cox proportional hazards models were self-rated health, ability to perform instrumental activities of daily living (IADLs), depressive symptoms, and cognitive functioning, controlling for age, sex, education, and number of prescription drugs. SETTING: A largely blue-collar rural community in southwestern Pennsylvania. PARTICIPANTS: A population-based cohort of 1064 adults, 67 years or older at the beginning of follow-up. MAIN OUTCOME MEASURES: Mortality at 3, 5, and 10 years (133, 218, and 482 deaths, respectively). RESULTS: Mortality rates were similar to those of the 1990 US population. Older age, male sex, IADL disability, and number of prescription drugs measured at baseline were significant predictors of mortality at all 3 follow-up end points. Depression at baseline predicted earlier (3- and 5-year) mortality but not later (10-year) mortality. The interaction between self-rated health and depression independently and strongly predicted mortality at all end points. Cognitive functioning predicted mortality only when IADL disability was excluded from the model. CONCLUSIONS: Age, sex, depression, and functional disability are strong and consistent independent predictors of mortality in older adults in the community, in addition to objective medical burden (prescription drugs). Depression alone predicts mortality in the shorter rather than longer term, but in combination with poor self-rating of health, it strongly predicts mortality at all end points.

Activities of Daily Living↗
PubMed2002

Data management and quality assurance for an International project: the Indo-US Cross-National Dementia Epidemiology Study.

BACKGROUND: Data management and quality assurance play a vital but often neglected role in ensuring high quality research, particularly in collaborative and international studies. OBJECTIVE: A data management and quality assurance program was set up for a cross-national epidemiological study of Alzheimer's disease, with centers in India and the United States. METHODS: The study involved (a) the development of instruments for the assessment of elderly illiterate Hindi-speaking individuals; and (b) the use of those instruments to carry out an epidemiological study in a population-based cohort of over 5000 persons. Responsibility for data management and quality assurance was shared between the two sites. A cooperative system was instituted for forms and edit development, data entry, checking, transmission, and further checking to ensure that quality data were available for timely analysis. A quality control software program (CHECKS) was written expressly for this project to ensure the highest possible level of data integrity. CONCLUSIONS: This report addresses issues particularly relevant to data management and quality assurance at developing country sites, and to collaborations between sites in developed and developing countries.

Alzheimer Disease↗
PubMed2002

Sensitivity and specificity of cognitive and functional screening instruments for dementia: the Indo-U.S. Dementia Epidemiology Study.

There is a shortage of adequate screening instruments for dementia in poorly educated populations and non-English-speaking groups. An epidemiological survey was conducted in a population-based, largely illiterate, sample of 5,126 individuals aged 55 and older in 28 villages in the rural community of Ballabgarh in northern India. All participants were administered a general mental status test, the Hindi Mental State Examination (HMSE), and a brief battery of neuropsychological tests. Their informants answered a questionnaire assessing functional ability, the Everyday Abilities Scale for India (EASI). Six hundred thirty-two participants underwent clinical diagnostic evaluation for dementia. We investigated whether the sensitivity, specificity, and predictive value for dementia of the mental status test could be improved by the addition of the brief neuropsychological test battery or the functional questionnaire, comparing the instruments alone and in combination. In participants who could be tested cognitively, the HMSE, the neuropsychological battery, and EASI had sensitivities of 81.3%, 81.3%, and 62.5%, respectively, with specificities of 60.2%, 74.5%, and 89.7%, respectively. The combination of all three was 93.8% sensitive and 41.8% specific. The sensitivity of the HMSE alone was nonsignificantly improved by the addition of either the EASI or the neuropsychological battery, whereas its specificity was significantly decreased by either addition. An advantage of the EASI was that it could also be administered to informants of subjects who were cognitively untestable. In this largely illiterate community, with a low prevalence of dementia, the combination of cognitive tests and a functional ability questionnaire had substantial value for population screening.

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PubMed2002

Use of lipid-lowering drugs in older adults with and without dementia: a community-based epidemiological study.

OBJECTIVES: To compare the use of lipid-lowering drugs in community-dwelling older adults with and without dementia. DESIGN: Comparison of lipid-lowering drug use by demented cases and nondemented controls based on secondary analysis of data from a longitudinal epidemiologic study. SETTING: Longitudinal study of a largely rural, low- socioeconomic-status, community-based cohort of older persons residing in the mid-Monongahela Valley of South-west Pennsylvania (the Monongahela Valley Independent Elders Survey). PARTICIPANTS: Eight hundred forty-five individuals of mean +/- standard deviation (SD) age of 80.5 +/- 4.6, participating in the fifth biennial wave of data collection. MEASUREMENTS: Demographics; medical history; medication regimen (including examination of prescription bottle labels); self-report of most recent visit to primary care physician (PCP); and standardized clinical assessment to determine presence of dementia, including Clinical Dementia Rating (CDR). RESULTS: One hundred seventy participants (20.1% of total subject cohort) had dementia, with a CDR of 0.5 or greater. Mean ages of demented and nondemented individuals were 83.5 +/- 5.1 and 79.8 +/- 4.2, respectively. Similar proportions, 87.7% and 89.5%, of these groups reported PCP visits in the previous year. Of the total sample, 9.4% (3.5% of the demented and 10.8% of the nondemented) were taking lipid-lowering drugs. After adjustment for age, sex, education, visit with PCP within the past year, and potential confounding clinical and lifestyle variables (self-reported heart disease, stroke or transient ischemic attacks, hypertension, smoking, and alcohol consumption), dementia was associated with a lower likelihood of taking a lipid-lowering drug (odds ratio = 0.39, 95% confidence interval = 0.16-0.95). In post hoc subgroup analyses, similar results were found when restricting lipid-lowering drugs to statins alone but were not statistically significant. Drug use was not associated with severity of dementia (CDR = 0.5 vs CDR >or= 1). CONCLUSIONS: Demented individuals were less likely than their nondemented counterparts to be taking lipid-lowering drugs. This finding could reflect different prescribing patterns by physicians for demented and nondemented patients or a possible protective effect of these drugs against dementia.

Age Factors↗
PubMedDate not supplied

Mild cognitive impairment and the 7 uses of epidemiology.

In 1907, Alzheimer's single case report of presenile dementia led to the condition being recognized as a rare disease of middle-aged people. In 1964, Roth and colleagues reported an epidemiologic survey showing that the same condition was in fact a relatively common disease of the elderly. In 1987, Katzman introduced the concept of brain reserve, suggesting how individuals could have Alzheimer disease pathology in their brains without clinically manifesting the disease. In 1999, Petersen described mild cognitive impairment (MCI) as an amnestic state, since broadened to include other cognitive deficits, which, in the majority of patients, was a prelude to the development of full-blown Alzheimer disease or other dementia. MCI today is in some ways analogous to Alzheimer disease a century ago. We recognize and describe MCI clinically, among patients with memory complaints, but we do not know its distribution, outcomes, and risk factors in the elderly population at large. All population-based studies to date have found MCI to be an unstable and heterogeneous entity with a far wider range of outcomes than in the clinical setting, including reversion to normal in a substantial proportion. However, these studies thus far have been purely descriptive, and retro-fitted on to existing studies of dementia, using measurements not necessarily appropriate for the assessment of MCI. This review will address what is known and what has yet to be determined about MCI from the perspectives of the classic 7 uses of epidemiology.

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PubMedDate not supplied

Exercise level and cognitive decline: the MoVIES project.

Growing evidence suggests that physical exercise may be protective against cognitive impairment and decline. A prospective study of a representative rural community sample (N = 1,146) aged 65+ years examined self-reported exercise habits and measured global cognitive function using the Mini-Mental State Examination (MMSE). A composite variable "exercise level" combining type, frequency, and duration of exercise was created with three levels: "high exercise" (aerobic exercise of > or = 30 minute duration > or = 3 times a week), "low exercise" (all other exercise groups), and "no exercise." Cognitive decline was defined as being in the 90 percentile of decline in this cohort, ie, declining by 3 or more MMSE points during the 2-year interval between two assessments. In a multiple regression model, high exercise level at the baseline assessment was negatively associated with, ie, was protective against, being in the group with the greatest amount of decline at the follow-up assessment, after adjusting for likely confounders (odds ratio = 0.39; 95% confidence interval, 0.19, 0.78). When high exercise was redefined using frequency as > or = 5 days per week as the threshold, as per the Surgeon General's guidelines, both low exercise and high exercise were negatively associated with cognitive decline. Exercise may have implications for prevention of cognitive decline.

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PubMedDate not supplied

Screening for cognitive impairment and depression in ethnically diverse older populations.

Considerable advances have been made over the past decade in developing and adapting instruments to measure cognitive functioning in individuals with a wide range of educational and racial/ethnic backgrounds in different countries. Similar approaches can be used to extend these assessments to groups that have not yet been studied. The critical issues are to ensure that methods are appropriately harmonized to the local context, that local norms are established, and that local expertise is brought to bear in instrument development/adaptation. Effective instruments are also available to screen for depression in the elderly but closer attention should be made to possible ethnic differences in item response on these scales. The ideal screening tool should be quick, inexpensive, painless, and socially/culturally acceptable to the population. It should also have desirable psychometric properties. Examples are provided from several international studies. The context, costs, and objectives of screening a given population should be considered when selecting a screening instrument and a threshold on the scale, whether for clinical or research purposes.

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PubMedDate not supplied

Hemoglobin levels and Alzheimer disease: an epidemiologic study in India.

OBJECTIVE: Anemia is common in developing countries, where populations are aging rapidly. The authors explored the cross-sectional relationship between hemoglobin concentration and Alzheimer disease (AD) in a rural elderly sample in Ballabgarh, India. METHODS: A clinical diagnostic evaluation for dementia and a hemoglobin estimation were performed in 605 persons selected by screening a larger community-based sample age 55+ years. Twenty-six participants met criteria for AD. RESULTS: Hemoglobin was inversely associated with AD after adjustment for age, sex, and literacy. CONCLUSION: Low hemoglobin is associated with AD and should be investigated further as a modifiable risk factor.

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PubMedDate not supplied

Sedative-hypnotic use of diphenhydramine in a rural, older adult, community-based cohort: effects on cognition.

OBJECTIVE: The authors sought to identify patterns and associations of prescription and over-the-counter sedative-hypnotic use in an older, rural, blue-collar, community-based cohort in southwestern Pennsylvania over 10 years. METHODS: A group of 1,627 individuals age 65 and over were recruited and assessed during 1987-1989 and re-assessed during approximately biennial waves. Data included sleep medications, demographics, depressive symptoms, sleep complaints, and cognitive functioning (Mini-Mental State Exam [MMSE]). RESULTS: At Waves 1 through 5, the mean age of the cohort increased from 73.4 to 80.5 years. Use of prescription sedative-hypnotics (primarily benzodiazepines) increased from 1.8% to 3.1%, and over-the-counter sedative-hypnotic use (primarily diphenhydramine) increased from 0.4% to 7.6%. At Wave 5 (1996-1998), 8.17% of the sample reported using diphenhydramine as a sleep aid. After adjusting for age and sex, diphenhydramine use was associated with higher education and more depressive symptoms, the latter becoming nonsignificant after controlling for initial insomnia. MMSE became significantly associated with diphenhydramine use when 143 subjects with dementia were excluded from the analysis. CONCLUSION: As the cohort aged, prescription sedative-hypnotic use remained relatively stable, whereas over-the-counter sedative use, principally diphenhydramine, increased substantially. The association of this drug with cognitive impairment in persons without dementia highlights its potential for causing adverse reactions in older adults.

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