Neurology May 2009 Volume 72 Issue 20

Objective: To test the hypothesis that use of antihypertensive medication is associated with lower Alzheimer disease (AD) neuropathology.Methods: This was a postmortem study of 291 brains limited to those with normal neuropathology or with uncomplicated AD neuropathology (i.e., without other dementia-associated neuropathology) in persons with or without hypertension (HTN) who were and were not treated with antihypertensive medications. Neuritic plaque (NP) and neurofibrillary tangle (NFT) densities, quantified in selected brain regions according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathologic criteria, with additional cortical NP counts, yielded 24 neuropathologic regional measures or summaries. Medicated hypertension (HTN-med; n = 77), nonmedicated HTN (HTN-nomed; n = 42), and non-HTN (no-HTN; n = 172) groups were compared by analyses of variance.Results: The HTN-med group had significantly less neuropathology than the no-HTN group. The no-HTN group averaged over 50% higher mean NP and NFT ratings, and double the mean NP count, of the HTN-med group. The HTN-nomed group had significantly more neuropathology than the HTN-med group, but not significantly less than the no-HTN group.Conclusions: There was substantially less Alzheimer disease (AD) neuropathology in the medicated hypertension group than the nonhypertensive group, which may reflect a salutary effect of antihypertensive medication against AD-associated neuropathology.(C)2009AAN Enterprises, Inc.

Objective: The need for biological markers of Alzheimer disease (AD) is constantly increasing. Proton magnetic resonance spectroscopy (1H-MRS) studies have provided consistent evidence for a reduction of the neuronal marker N-acetylaspartate (NAA) in patients with AD. Within the German Competence Network on Dementia, we conducted a 1H-MRS study in patients with mild dementia and mild cognitive impairment (MCI) at four sites to investigate the multicenter feasibility of 1H-MRS.Methods: In total, 130 patients with dementia (98 AD, 32 non-AD), 136 subjects with MCI (70 of AD type, 66 of non-AD type), and 45 unimpaired control subjects were included. Single-volume 1H-MRS of the left medial temporal lobe was performed at long and short echo times. Metabolites were quantified and metabolic ratios were determined.Results: We found a significant reduction of NAA concentration in patients with AD as compared to healthy volunteers and compared to patients with MCI of AD type. NAA/Cr (creatine/phosphocreatine) was also lower in patients with AD compared to control subjects. NAA, choline compounds, and Cr were lower in patients with AD compared to patients with non-AD dementia.Conclusions: We demonstrated the multicenter feasibility of proton magnetic resonance spectroscopy (1H-MRS) of the medial temporal lobe in mild dementia and mild cognitive impairment, which is a prerequisite for the application of 1H-MRS in large-scale clinical trials. Since the concentration measures of the metabolites are adjusted for brain tissue volume, these findings are indicators of biochemical pathology beyond brain atrophy.(C)2009AAN Enterprises, Inc.

Background: Whether recurrent epileptic seizures induce brain damage is debated. Disease progression in epilepsy has been evaluated only in a few community-based studies involving patients with seizures well controlled by medication. These studies concluded that epilepsy does not inevitably lead to global cerebral damage.Objective: To track the progression of neocortical atrophy in pharmacoresistant temporal lobe epilepsy (TLE) using longitudinal and cross-sectional designs.Methods: Using a fully automated measure of cortical thickness on MRI, we studied a homogeneous sample of patients with pharmacoresistant TLE. In the longitudinal analysis (n = 18), fixed-effect models were used to quantify cortical atrophy over a mean interscan interval of 2.5 years (range = 7 to 90 months). In the cross-sectional analysis (n = 121), we correlated epilepsy duration and thickness. To dissociate normal aging from pathologic progression, we compared aging effects in TLE to healthy controls.Results: The longitudinal analysis mapped progression in ipsilateral temporopolar and central and contralateral orbitofrontal, insular, and angular regions. In patients with more than 14 years of disease, atrophy progressed more rapidly in frontocentral and parietal regions that in those with shorter duration. The cross-sectional study showed progressive atrophy in the mesial and superolateral frontal, and parietal cortices.Conclusions: Our combined cross-sectional and longitudinal analysis in patients with pharmacoresistant temporal lobe epilepsy demonstrated progressive neocortical atrophy over a mean interval of 2.5 years that is distinct from normal aging, likely representing seizure-induced damage. The cumulative character of atrophy underlies the importance of early surgical treatment in this group of patients.(C)2009AAN Enterprises, Inc.

Background: Health-related quality of life (HRQOL) is reduced in multiple sclerosis (MS). It is unclear whether HRQOL is associated with white matter lesion burden or measures of brain atrophy.Methods: A cross-sectional baseline analysis of 507 patients with MS in a prospective cohort study at the University of California, San Francisco was performed. Multivariate linear regression models were used to determine whether MRI measures were associated with the Emotional Well-Being and Thinking/Fatigue subscale scores of the Functional Assessment in Multiple Sclerosis, a validated HRQOL measure in MS. The difference in each MRI metric associated with a minimal clinically important difference in each HRQOL subscale was calculated.Results: Higher T1 lesion load (15 mL; p = 0.024), normalized T1 lesion volume (20 mL; p = 0.016), or T2 lesion load (25 mL; p = 0.028) was associated with worse scores for Emotional Well-Being. Meaningfully lower scores on this subscale were correlated with lower normalized gray matter volume (118 mL; p = 0.037). Reduced Thinking/Fatigue scores were associated with higher normalized T1 lesion volume (21 mL; p = 0.024), or T2 lesion load (22 mL; p = 0.010) and with lower normalized gray matter (87 mL; p = 0.004), white matter (85 mL; p = 0.025), or brain parenchymal (98 mL; p = 0.001) volume.Conclusions: Aspects of health-related quality of life (HRQOL) in multiple sclerosis are associated with MRI evidence of white matter lesions and brain atrophy. These findings strengthen the argument for the use of HRQOL outcome measures in trials and suggest that lesion burden on conventional MRI is important for HRQOL.(C)2009AAN Enterprises, Inc.

Background: Lacunar stroke is common, but the etiology of the small vessel abnormality is unknown. Retinal vessels share ontogeny, size, and physiologic characteristics with cerebral small vessels, and retinopathy is associated with stroke. We compared retinal microvessel appearance as a surrogate for cerebral small vessels in patients with lacunar and large artery cortical ischemic stroke.Methods: We prospectively recruited patients with lacunar ischemic stroke and cortical stroke controls. We took digital retinal photographs of each eye. We assessed central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) diameters and arteriovenous ratios (AVRs) using semiautomated computer software methods and quantified arteriovenous nicking and focal arteriolar narrowing.Results: Among 212 patients (105 lacunar, 107 cortical strokes) of mean age 68 years (SD 12 years), AVR was decreased (0.76 vs 0.78, p = 0.03) and CRVE was increased (44.9 pixels/218 [mu]m vs 42.8 pixels/208 [mu]m, p = 0.01) in lacunar patients compared with cortical patients, but CRAE did not differ (33.2 pixels/161 [mu]m vs 33.7 pixels/163 [mu]m, p = 0.4). On multivariable analysis, increased CRVE was associated with lacunar stroke subtype (p = 0.03) and younger age (p < 0.001) after correcting for other vascular risk factors. Arteriovenous nicking and focal arteriolar narrowing did not differ between ischemic stroke subtypes.Conclusions: Retinal venules are wider and arteriovenous ratios are smaller in patients with lacunar strokes compared with those in patients with cortical strokes.(C)2009AAN Enterprises, Inc.