Neurology August 2009 Volume 73 Issue 8

Background: We evaluated the cross-sectional relationship of blood pressure (BP) components with cognitive impairment after adjusting for potential confounders.Methods: Reasons for Geographic and Racial Differences in Stroke (REGARDS) is a national, longitudinal population cohort evaluating stroke risk in 30,228 black and white men and women >=45 years old. During the in-home visit, BP measurements were taken as the average of 2 measurements using a standard aneroid sphygmomanometer. Excluding participants with prior stroke or TIA, the present analysis included 19,836 participants (enrolled from December 2003 to March 2007) with complete baseline physical and cognitive evaluations. Incremental logistic models examined baseline relationships between BP components (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) and impaired cognitive status (score of <=4 on 6-Item Screener) after adjusting for demographic and environmental characteristics, cardiovascular risk factors, depressive symptoms, and current use of any antihypertensive medication.Results: Higher DBP levels were associated with impaired cognitive status after adjusting for demographic and environmental characteristics, risk factors, depressive symptoms, and antihypertensive medications. An increment of 10 mm Hg in DBP was associated with a 7% (95% confidence interval [CI] 1%-14%, p = 0.0275) higher odds of cognitive impairment. No independent association was identified between impaired cognitive status and SBP (odds ratio [OR] 1.02, 95% CI 0.99-1.06) or PP (OR 0.99, 95% CI 0.95-1.04). There was no evidence of nonlinear relationships between any of the BP components and impaired cognitive status. There was no interaction between age and the relationship of impaired cognitive status with SBP (p = 0.827), DBP (p = 0.133), or PP (p = 0.827) levels.Conclusions: Higher diastolic blood pressure was cross-sectionally and independently associated with impaired cognitive status in this large, geographically dispersed, race- and sex-balanced sample of stroke-free individuals.(C)2009AAN Enterprises, Inc.

Background: Multiple sclerosis (MS) is a complex neurologic disease with a striking geographical distribution. In Canada, prevalence is high in Caucasians of Northern European ancestry and uncommon in North American Aboriginals, many of whom now have Caucasian admixture.Methods: The population-based Canadian Collaborative Project on the Genetic Susceptibility to MS provided the characteristics of 58 individuals with 1 Caucasian and 1 North American Aboriginal parent from a database of 30,000 MS index cases.Results: We found that MS index cases with a Caucasian mother and a North American Aboriginal father had a higher sib recurrence risk and greater F:M sex ratio (p = 0.043) than patients with a North American Aboriginal mother and Caucasian father.Conclusions: Maternal parent-of-origin effects in multiple sclerosis disease etiology previously seen in studies of half-siblings and avuncular pairs are also seen in Caucasian-North American Aboriginal admixture matings and warrant further investigation. A differential influence of maternal risk transmission on the sex ratio of affected offspring is implied. The method of analysis used may have broader implications for detection of parent-of-origin effects in admixture cohorts.(C)2009AAN Enterprises, Inc.

Objective: To determine whether whole-brain, event-related fMRI can distinguish healthy older adults with known Alzheimer disease (AD) risk factors (family history, APOE [varepsilon]4) from controls using a semantic memory task involving discrimination of famous from unfamiliar names.Methods: Sixty-nine cognitively asymptomatic adults were divided into 3 groups (n = 23 each) based on AD risk: 1) no family history, no [varepsilon]4 allele (control [CON]); 2) family history, no [varepsilon]4 allele (FH); and 3) family history and [varepsilon]4 allele (FH+[varepsilon]4). Separate hemodynamic response functions were extracted for famous and unfamiliar names using deconvolution analysis (correct trials only).Results: Cognitively intact older adults with AD risk factors (FH and FH+[varepsilon]4) exhibited greater activation in recognizing famous relative to unfamiliar names than a group without risk factors (CON), especially in the bilateral posterior cingulate/precuneus, bilateral temporoparietal junction, and bilateral prefrontal cortex. The increased activation was more apparent in the FH+[varepsilon]4 than in the FH group. Unlike the 2 at-risk groups, the control group demonstrated greater activation for unfamiliar than familiar names, predominately in the supplementary motor area, bilateral precentral, left inferior frontal, right insula, precuneus, and angular gyrus. These results could not be attributed to differences in demographic variables, cerebral atrophy, episodic memory performance, global cognitive functioning, activities of daily living, or depression.Conclusions: Results demonstrate that a low-effort, high-accuracy semantic memory activation task is sensitive to Alzheimer disease risk factors in a dose-related manner. This increased activation in at-risk individuals may reflect a compensatory brain response to support task performance in otherwise asymptomatic older adults.(C)2009AAN Enterprises, Inc.

Background: Families associated with missense mutations in the valosin-containing protein (VCP) present with a rare autosomal dominant multisystem disorder of frontotemporal lobar degeneration (FTLD), inclusion body myopathy (IBM), and Paget disease of bone (PDB), referred to as IBMPFD.Methods: We used exon-based genomic DNA sequencing to test for VCP mutations in 123 unrelated Belgian patients with FTLD and their relatives, and the absence of such mutations in 157 control individuals. We analyzed haplotype sharing among mutation carriers by genotyping 8 microsatellite markers in the VCP locus. We obtained family history and clinical and pathologic data using established diagnostic instruments.Results: Mutation analysis of VCP identified 2 Belgian patients with FTLD carrying the p.Arg159His mutation, which segregated in their families. In one family, patients presented with FTLD only, whereas in the other family, patients developed FTLD, PDB, or both without signs of IBM for any of the mutation carriers. We had previously identified p.Arg159His in an Austrian family with patients exhibiting both IBM and PDB. Haplotype sharing analysis indicated that the 3 p.Arg159His families are unrelated. Clinical follow-up of the Austrian family identified dementia symptoms in 1 patient. Autopsy data of 3 patients of the 2 Belgian families revealed FTLD pathology with numerous ubiquitin-immunoreactive, intranuclear inclusions and dystrophic neurites staining positive for TDP-43 protein.Conclusions: In 3 unrelated families with IBMPFD segregating VCP p.Arg159His, we observed a high degree of clinical heterogeneity and variable penetrance of the 3 cardinal clinical phenotypes: inclusion body myopathy, Paget disease of bone, and frontotemporal lobar degeneration. In contrast, the neuropathologic phenotype was consistent with FTLD-TDP type 4.(C)2009AAN Enterprises, Inc.

Background: It is reported in some individual patients that vestibular stimuli can trigger migraine attacks. This study used a case-control design to examine systematically the hypothesis that vertigo induced by vestibular stimulation (rotation/caloric testing) can act as a specific migraine trigger.Methods: A total of 123 new patients attending neuro-otology or neurology clinics were studied with questionnaires and physician interview to ascertain migraine history according to International Headache Society criteria. A total of 79 who underwent rotation/caloric vestibular testing (test group) were compared with 44 control patients in whom no such testing was carried out (control group). The principal outcome measure was the occurrence of a migraine attack within 24 hours of exposure to vestibular stimulation.Results: Of those participants with a past history of migraines, 19/39 (49%) of the test group experienced a migraine in the study time window, compared with 1/21 (5%) of the control group. Binary logistic regression analysis confirmed that vestibular testing was associated (p < 0.05) with migraine attacks.Conclusions: The results indicate that induced vertigo can act as a migraine trigger, a finding with implications for the diagnosis of patients with episodic vertigo and migraine headache. While such patients may well have basilar migraine or migrainous vertigo, alternatively, another disorder causing episodic vertigo (e.g., benign paroxysmal positional vertigo or Meniere disease) may be triggering migraine headaches.(C)2009AAN Enterprises, Inc.