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issn:0003-99.2
1.  Association of Apolipoprotein E Genotype and Alzheimer Disease in African Americans 
Archives of neurology  2006;63(3):431-434.
Background
Alzheimer disease (AD) is the most frequent cause of dementia. Even though the incidence of AD in the African American population is similar to or higher than that in persons of European descent, AD in African Americans is understudied. Identification of genetic risk factors in African Americans is essential for understanding the etiology of AD.
Objective
To determine the effect of apolipoprotein E (APOE) genotype on the risk of AD in elderly African Americans.
Design
Population-based longitudinal study of AD.
Setting
Indianapolis, Ind.
Participants
African Americans 65 years and older.
Main Outcome Measures
APOE genotype and diagnosis of AD.
Results
The APOE genotype was determined in 1822 samples. Of these, 690 were clinically evaluated: 318 were normal, and 162 had a diagnosis of AD. The presence of APOE ε4 was significantly associated with increased risk of AD (ε3/ε4: OR, 2.32; 95% confidence interval [CI], 1.41–3.82; and ε4/ε4: OR, 7.19; 95% CI, 3.00–17.29, compared with the ε3/ε3 genotype). There was also a significant protective effect with APOE ε2 (ε2/ε2 and ε2/ε3: OR, 0.42; 95% CI, 0.20–0.89).
Conclusions
These findings are in marked contrast to the lack of association between APOE and AD in the Ibadan, Nigeria, sample of this project. These results suggest that other genetic factors and different environmental influences may play a role in the risk for AD in individuals of African ancestry.
doi:10.1001/archneur.63.3.431
PMCID: PMC3203415  PMID: 16533971
2.  Phenotypic Variability Among Adult Siblings With Sjögren-Larsson Syndrome 
Archives of neurology  2006;63(2):278-280.
Background
Sjögren-Larsson syndrome (SLS) is an early childhood–onset disorder with ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy caused by the deficiency of fatty aldehyde dehydrogenase due to mutations in the ALDH3A2 gene (the gene that encodes microsomal fatty aldehyde dehydrogenase). Cerebral proton magnetic resonance spectroscopy in those with SLS demonstrates an abnormal white matter peak at 1.3 ppm, consistent with long-chain fatty alcohol accumulation.
Objective
To define the clinical course and proton magnetic resonance spectroscopic findings of SLS in adults.
Design and Setting
Case series in a tertiary care center.
Patients
Six siblings of a consanguineous Arab family with early childhood–onset SLS who carry the 682C→T mutation in the ALDH3A2 gene were reinvestigated in adulthood.
Results
The 6 affected siblings ranged in age from 16 to 36 years. All exhibited the typical clinical and imaging manifestations of SLS, but their severity markedly varied. Neurological involvement was apparently nonprogressive, and its severity showed no correlation with age. Cerebral proton magnetic resonance spectroscopy showed a lipid peak at 1.3 ppm, with decreasing intensity in the older siblings.
Conclusion
These observations document significant clinical variability and the nonprogressive neurological course of SLS in adult siblings with the same ALDH3A2 genotype, and demonstrate possible correlation of proton magnetic resonance spectroscopic changes with age, suggesting unknown pathogenic mechanisms to compensate for the responsible biochemical defect in this disease.
doi:10.1001/archneur.63.2.278
PMCID: PMC3086176  PMID: 16476818
3.  Mediterranean Diet, Alzheimer Disease, and Vascular Mediation 
Archives of neurology  2006;63(12):1709-1717.
Objectives
To examine the association between the Mediterranean diet (MeDi) and Alzheimer disease (AD) in a different AD population and to investigate possible mediation by vascular pathways.
Design, Setting, Patients, and Main Outcome Measures
A case-control study nested within a community-based cohort in New York, NY. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD status (194 patients with AD vs 1790 nondemented subjects) in logistic regression models that were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index (calculated as weight in kilograms divided by height in meters squared). We investigated whether there was attenuation of the association between MeDi and AD when vascular variables (stroke, diabetes mellitus, hypertension, heart disease, lipid levels) were simultaneously introduced in the models (which would constitute evidence of mediation).
Results
Higher adherence to the MeDi was associated with lower risk for AD (odds ratio, 0.76; 95% confidence interval, 0.67–0.87; P<.001). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had an odds ratio of 0.47 (95% confidence interval, 0.29–0.76) and those at the highest tertile an odds ratio of 0.32 (95% confidence interval, 0.17–0.59) for AD (P for trend <.001). Introduction of the vascular variables in the model did not change the magnitude of the association.
Conclusions
We note once more that higher adherence to the MeDi is associated with a reduced risk for AD. The association does not seem to be mediated by vascular comorbidity. This could be the result of either other biological mechanisms (oxidative or inflammatory) being implicated or measurement error of the vascular variables.
doi:10.1001/archneur.63.12.noc60109
PMCID: PMC3024906  PMID: 17030648
5.  Visual Hallucinations in Posterior Cortical Atrophy 
Archives of neurology  2006;63(10):1427-1432.
Objective
To compare clinical and imaging features of patients with posterior cortical atrophy (PCA) with and without well-formed visual hallucinations.
Setting
Tertiary care medical center
Methods
Fifty-nine patients fulfilling criteria for PCA were retrospectively identified, and divided into two groups based on the presence (N=13) and absence (N=46) of visual hallucinations. Both groups were then compared statistically for clinical differences, as well as with voxel-based morphometry (VBM) for imaging differences.
Results
In PCA patients with hallucinations, parkinsonism and rapid eye movement sleep behavior disorder occurred more frequently (p<0.0001), as did myoclonic jerks (p=0.0002). VBM analysis showed greater atrophy in a network of structures, including the primary visual cortex, lentiform nuclei, thalamus, basal forebrain and midbrain in the patients with hallucinations.
Conclusions
Hallucinations in patients with PCA are associated with parkinsonism, rapid eye movement sleep behavior disorder, and myoclonic jerks. The results from the VBM analysis suggest that hallucinations in PCA cannot be exclusively attributed to atrophy of the posterior association cortices and may involve a circuit of thalamocortical connections.
doi:10.1001/archneur.63.10.1427
PMCID: PMC2748870  PMID: 17030659
Parkinsonism; Thalamus; Myoclonic jerks; REM sleep; Voxel based morphometry
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.  Dopamine Agonist Use is Associated with Impulse Control Disorders in Parkinson’s Disease 
Archives of neurology  2006;63(7):969-973.
Objective
To determine the frequency and correlates of impulse control disorders (ICDs) in Parkinson’s disease (PD).
Design
An unstructured screening interview for ICDs (compulsive gambling, buying, and sexual behavior) followed by a telephone-administered structured interview for screen-positive patients.
Setting
Two university-affiliated movement disorders centers.
Participants
A convenience sample of 272 patients with idiopathic PD who were screened for psychiatric complications.
Main Outcome Measures
Presence of compulsive gambling, buying, or sexual behavior as assessed by the Minnesota Impulsive Disorders Interview.
Results
Eighteen (6.6%) PD patients met criteria for an ICD at some point during the course of PD, including 11 (4.0%) with an active ICD. Compulsive gambling and compulsive sexual behavior were equally common. In a multivariate model, treatment with a dopamine agonist (P = .01) and a history of ICD symptomatology prior to PD onset (P = .02) predicted current ICD. There were no differences between the dopamine agonists in their association with ICDs (P = .21), and daily doses of dopamine agonists were higher in patients with an ICD than in dopamine agonist-treated patients without an ICD (P < .001).
Conclusions
PD patients treated with a dopamine agonist should be made aware of the risk of developing an ICD and monitored clinically. As dopamine agonists are increasing being used for other indications, future research should assess the dopamine agonist-associated risk for ICDs in other populations.
doi:10.1001/archneur.63.7.969
PMCID: PMC1761054  PMID: 16831966
8.  Lewy Body Pathology in Familial Alzheimer Disease 
Archives of neurology  2006;63(3):370-376.
Background
The origin and significance of Lewy bodies and neurites (Lewy body pathology [LBP]) in Alzheimer disease (AD) are poorly understood.
Objective
To examine LBP in the brainstem, limbic cortex, and neocortex of a large number of familial AD cases with mutations in 2 presenilin (PSEN) genes.
Methods
Twenty-five familial AD cases with 9 known PSEN 1 mutations and 14 familial AD cases with a single PSEN 2 mutation (N141I) were examined for LBP using α-synuclein immunohistochemistry and sampling of multiple brainstem and cortical regions.
Results
The amygdala was the most vulnerable site for LBP. In fact, virtually all (24 [96%] of 25 cases) of the PSEN 1 mutation cases had LBP in the amygdala. The PSEN 1 mutation cases also had more frequent LBP in the amygdala and neocortex than those with the PSEN 2 mutation. However, within families with a single mutation of either PSEN 1 or PSEN 2, there was frequent variability of the LBP.
Conclusion
These findings suggest that there are genetic influences on the presence of LBP in familial AD as demonstrated by the differences between PSEN 1 and PSEN 2 mutation cases.
doi:10.1001/archneur.63.3.370
PMCID: PMC1892620  PMID: 16533963

Results 1-8 (8)