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1.  Familial Aggregation of Dementia With Lewy Bodies 
Archives of Neurology  2011;68(1):90-93.
Background
Familial aggregation of dementia with Lewy bodies (DLB) remains unclear.
Objectives
To determine the degree of family aggregation of DLB by comparing DLB risk between siblings of probands with clinically diagnosed DLB and siblings of probands with clinically diagnosed Alzheimer disease in a cohort of Caribbean Hispanic families and to explore the degree of aggregation of specific clinical manifestations (ie, cognitive fluctuations, visual hallucinations, and parkinsonism) in DLB.
Design
Familial cohort study.
Setting
Academic research.
Patients
We separately compared risks of possible DLB, probable DLB, and clinical core features of DLB (cognitive fluctuations, visual hallucinations, and parkinsonism) between siblings of probands with clinically diagnosed DLB (n=344) and siblings of probands with clinically diagnosed Alzheimer disease (n=280) in 214 Caribbean Hispanic families with extended neurologic and neuropsychological assessment.
Main Outcome Measures
We applied general estimating equations to adjust for clustering within families. In these models, age and proband disease status were independent variables, and disease status of siblings was the measure of disease risk and the dependent variable.
Results
Compared with siblings of probands having clinically diagnosed Alzheimer disease, siblings of probands having clinically diagnosed DLB had higher risks of probable DLB (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.04–5.04) and visual hallucinations (2.32; 1.16–4.64). They also had increased risks of possible DLB (OR, 1.51; 95% CI, 0.97–2.34) and cognitive fluctuations (1.55; 0.95–2.53).
Conclusions
Dementia with Lewy bodies and core features of DLB aggregate in families. Compared with siblings of probands having clinically diagnosed AD, siblings of probands having clinically diagnosed DLB are at increased risks of DLB and visual hallucinations. These findings are an important step in elucidating the genetic risk factors underlying DLB and in delineating DLB from other neurodegenerative diseases, such as Alzheimer disease.
doi:10.1001/archneurol.2010.319
PMCID: PMC3268781  PMID: 21220678
2.  A Summary Risk Score for the Prediction of Alzheimer Disease in Elderly Persons 
Archives of neurology  2010;67(7):835-841.
Objective
To develop a simple summary risk score for the prediction of Alzheimer disease in elderly persons based on their vascular risk profiles.
Design
A longitudinal, community-based study.
Setting
New York, New York.
Patients
One thousand fifty-one Medicare recipients aged 65 years or older and residing in New York who were free of dementia or cognitive impairment at baseline.
Main Outcome Measures
We separately explored the associations of several vascular risk factors with late-onset Alzheimer disease (LOAD) using Cox proportional hazards models to identify factors that would contribute to the risk score. Then we estimated the score values of each factor based on their βcoefficients and created the LOAD vascular risk score by summing these individual scores.
Results
Risk factors contributing to the risk score were age, sex, education, ethnicity, APOE ε4 genotype, history of diabetes, hypertension or smoking, high-density lipoprotein levels, and waist to hip ratio. The resulting risk score predicted dementia well. According to the vascular risk score quintiles, the risk to develop probable LOAD was 1.0 for persons with a score of 0 to 14 and increased 3.7-fold for persons with a score of 15 to 18, 3.6-fold for persons with a score of 19 to 22, 12.6-fold for persons with a score of 23 to 28, and 20.5-fold for persons with a score higher than 28.
Conclusions
While additional studies in other populations are needed to validate and further develop the score, our study suggests that this vascular risk score could be a valuable tool to identify elderly individuals who might be at risk of LOAD. This risk score could be used to identify persons at risk of LOAD, but can also be used to adjust for confounders in epidemiologic studies.
doi:10.1001/archneurol.2010.136
PMCID: PMC3068839  PMID: 20625090
3.  Association of Higher Levels of High-Density Lipoprotein Cholesterol in Elderly Individuals and Lower Risk of Late-Onset Alzheimer Disease 
Archives of neurology  2010;67(12):1491-1497.
Objective
To reexamine the association of lipid levels with Alzheimer disease (AD) using Cox proportional hazards models.
Design
Prospective cohort study.
Setting
Northern Manhattan, New York.
Participants
One thousand one hundred thirty elderly individuals free of cognitive impairment at baseline.
Main Outcome Measure
High-density lipoprotein cholesterol (HDL-C) levels.
Results
Higher levels of HDL-C (>55 mg/dL) were associated with a decreased risk of both probable and possible AD and probable AD compared with lower HDL-C levels (hazard ratio, 0.4; 95% confidence interval, 0.2–0.9; P=.03 and hazard ratio, 0.4; 95% confidence interval, 0.2–0.9; P=.03). In addition, higher levels of total and non–HDL-C were associated with a decreased risk of AD in analyses adjusting for age, sex, education, ethnic group, and APOEe4 genotype.
Conclusion
High HDL-C levels in elderly individuals may be associated with a decreased risk of AD.
doi:10.1001/archneurol.2010.297
PMCID: PMC3065942  PMID: 21149810
4.  Relation of Plasma Lipids to Alzheimer Disease and Vascular Dementia 
Archives of neurology  2004;61(5):705-714.
Background
The relation between plasma lipid levels and Alzheimer disease (AD) and vascular dementia (VaD), and the impact of drugs to lower lipid levels remains unclear.
Objective
To investigate the relation between plasma lipid levels and the risk of AD and VaD and the impact of drugs to lower lipid levels on this relationship.
Design and Setting
Cross-sectional and prospective community-based cohort studies.
Participants
Random sample of 4316 Medicare recipients, 65 years and older, residing in northern Manhattan, NY.
Main Outcome Measures
Vascular dementia and AD according to standard criteria.
Results
Elevated levels of non–high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospective analyses. Higher levels of total cholesterol were associated with a decreased risk of incident AD after adjustment for demographics, apolipoprotein E genotype, and cardiovascular risk factors. Treatment with drugs to lower lipid levels did not change the disease risk of either disorder.
Conclusions
We found a weak relation between non–HDL-C, LDL-C, and HDL-C levels and the risk of VaD. Lipid levels and the use of agents to lower them do not seem to be associated with the risk of AD.
doi:10.1001/archneur.61.5.705
PMCID: PMC2696387  PMID: 15148148
5.  Hypertension and the Risk of Mild Cognitive Impairment 
Archives of neurology  2007;64(12):1734-1740.
Background and Objective
There are conflicting data relating hypertension to the risk of Alzheime's disease (AD). We sought to explore whether hypertension is associated with the risk of mild cognitive impairment (MCI), an intermediate stage to dementia.
Design and Setting
Prospective community-based cohort study conducted in northern Manhattan.
Methods
Multivariate proportional hazards regression analyses, relating hypertension to incident all-cause MCI, amnestic MCI, and non-amnestic MCI in 918 persons without prevalent MCI at baseline followed for a mean of 4.7 years.
Results
There were 334 cases of incident MCI, 160 cases of amnestic MCI and 174 cases of non-amnestic MCI during 4337 person years of follow-up. Hypertension was associated with an increased risk of all-cause MCI (HR 1.4, 95% CI 1.06-1.77, p=0.02) and non-amnestic MCI (HR 1.7, 95% CI 1.13-2.42, p=0.009) after adjusting for age and gender. Both associations were slightly attenuated in models additionally adjusting for stroke and other vascular risk factors. There was no association between hypertension and the risk of amnestic MCI (HR 1.1, 95% CI 0.79-1.63, p=0.49). Consistent with this association, hypertension was related with the slope of change in an executive ability score, but not with memory or language scores. There was no effect modification of the association between hypertension and MCI by APOEε4 genotype or use of antihypertensive medication.
Conclusion
A history of hypertension is related to a higher risk of MCI. The association seems to be stronger with the non-amnestic than the amnestic component of MCI. These findings suggest that prevention and treatment of hypertension may have an important impact in lowering the risk of cognitive impairment.
doi:10.1001/archneur.64.12.1734
PMCID: PMC2672564  PMID: 18071036
blood pressure; hypertension; mild cognitive impairment
6.  Stroke and Memory Performance in Elderly without Dementia 
Archives of neurology  2006;63(4):571-576.
Background
There is conflicting data showing that stroke is associated with a higher risk of dementia and a more severe decline in persons with cognitive impairment. However, if cerebrovascular disease is directly related to cognitive decline in the absence of cognitive impairment or dementia remains unclear.
Objective
To examine the association between stroke and changes in cognitive function over time in elderly persons without dementia at baseline.
Design
The results of neuropsychological tests from several intervals over a five-year-period were clustered into domains of memory, abstract/visuospatial and language in 1271 elderly without dementia or cognitive decline. Stroke was related to the slope of performance in each cognitive domain using generalized estimating equations.
Results
Memory performance declined over time while abstract/visuospatial and language performance remained stable over the study period. Stroke was associated with a more rapid decline in memory performance, while there was no association between stroke and decline in abstract/visuospatial or language performance. The association between stroke and decline in memory performance was strongest for men and for persons without an APOE4 allele. A significant association between stroke and decline in abstract/visuospatial performance was also observed for persons without the APOE-e4 allele.
Conclusion
A history of stroke is related to a progressive decline in memory and abstract/visuospatial performance especially among men and those without an APOE-e4 allele.
doi:10.1001/archneur.63.4.571
PMCID: PMC2669794  PMID: 16606771
stroke; memory performance; cognitive performance
7.  Comparison of Clinical Manifestation in Familial Alzheimer's disease and Dementia with Lewy Bodies 
Archives of neurology  2008;65(12):1634-1639.
Background
The clinical delineation of Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) remains unclear.
Objective
To compare the neuropsychological profiles of patients with clinically diagnosed Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
Methods
We first compared measures of memory, orientation, language, executive, visual perception and visual construction function between persons with DLB and AD in two Caribbean Hispanic cohorts, including a family dataset (DLB =89; AD: n=118) and an epidemiologic dataset (DLB: n=70; AD: n=157). DLB in the family sample was further divided into i) families with two or more affected family members (DLB), or ii) one affected family member (DLB). To determine whether observed differences in cognitive profiles were driven by heritable factors, we then repeated the analyses in the epidemiologic cohort excluding all familial cases. We applied general linear models adjusting for age, sex, education, disease duration, and APOE-ε4 genotype.
Results
Persons with DLB were in both cohorts more severely impaired in orientation, visual construction and non verbal reasoning after controlling for potential confounders. Persons with 2 or more DLB cases per family had the most severe impairment in episodic and semantic memory, followed by those with one DLB case per family, then by those with AD. When familial AD and DLB cases were excluded from the analysis in the epidemiologic cohort, the differences between the AD and DLB groups persisted but were attenuated.
Conclusions
Compared to persons with AD, persons with DLB are more severely impaired in various cognitive domains, particularly orientation, visual perception and visual construction. The difference appears strong in familial rather than sporadic DLB. Whether this divergence in cognitive functions is caused by gene-gene or gene-environmental interactions remains unclear.
doi:10.1001/archneur.65.12.1634
PMCID: PMC2633487  PMID: 19064751
8.  Measures of adiposity and dementia risk in the elderly 
Archives of neurology  2007;64(3):392-398.
Background
Studies relating adiposity to dementia are conflicting. We explored the associations of body mass index (BMI) waist circumference (WC), and weight change to dementia, probable Alzheimer’s disease (AD), and dementia associated with stroke (DAS).
Methods
Persons without dementia were followed for 5 years; 893 persons had BMI, 907 persons had WC, and 709 persons had a second weight measurement. Dementia was ascertained using standard methods. Cox regression was used for analyses using follow-up as time-to-event, adjusting for demographics, and APOE-ɛ4.
Results
Compared to persons in the first quartile of BMI, persons in the third quartile had a lower dementia and AD risk, and persons in the second quartile had a lower DAS risk. The association between BMI and dementia resembled a U-shape in those < 76 years, while dementia risk decreased with higher BMI in those ≥ 76 years. The 4th quartile of WC was related to a higher DAS risk in the whole sample, and to dementia and AD in persons < 76 years. Weight loss was related to a higher dementia and DAS risk, and weight gain was related to a higher DAS risk only.
Conclusions
The prospective association between adiposity and dementia differs depending on the anthropometric measure used and is modified by age. This may explain previous conflicting reports.
doi:10.1001/archneur.64.3.392
PMCID: PMC1821350  PMID: 17353383

Results 1-8 (8)