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This Month in Archives of Neurology |

This Month in Archives of Neurology FREE

Arch Neurol. 2012;69(7):813-814. doi:10.1001/archneurol.2011.1464.
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PLASMA AMYLOID-Β AS A PREDICTOR OF DEMENTIA AND COGNITIVE DECLINE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Koyama and colleaguesArticle conduct a systematic review and meta-analysis of relevant prospective studies to determine whether plasma amyloid-β levels may predict development of dementia, Alzheimer disease (AD), and cognitive decline. They find that the literature indicates that plasma Aβ42:Aβ40 ratios predict development of AD and dementia. However, significant heterogeneity in the meta-analysis underlines the need for substantial further investigation of plasma amyloid-β levels as a preclinical biomarker.

ANTIOXIDANTS FOR ALZHEIMER DISEASE: A RANDOMIZED CLINICAL TRIAL WITH CEREBROSPINAL FLUID BIOMARKER MEASURES

Galasko et alArticle evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers. They report that antioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in subjects treated for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted.

LONG-TERM OUTCOMES OF CHRONIC LYMPHOCYTIC INFLAMMATION WITH PONTINE PERIVASCULAR ENHANCEMENT RESPONSIVE TO STEROIDS (CLIPPERS) IN A CONSECUTIVE SERIES OF 12 PATIENTS

Taieb and colleaguesArticle describe the disease course of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). They indicate that CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged prednisolone therapy prevents further relapses. Editorial perspective is provided by B. Mark Keegan, MD, FRCPC, and Sean J. Pittock, MDArticle.

SHAPES OF THE TRAJECTORIES OF 5 MAJOR BIOMARKERS OF ALZHEIMER DISEASE

Jack et alArticle characterize the shape of the trajectories of Alzheimer disease biomarkers as a function of Mini-Mental State Examination (MMSE) score. They show that biomarker trajectory shapes by MMSE score were complex and were affected by interactions with age and APOE status. Nonlinearity was found in several baseline effects models. Nonconstant within-subject rates of biomarker change were found in only 1 model, likely owing to limited within-subject longitudinal follow-up. Creating reliable models that describe the full trajectories of Alzheimer disease biomarkers will require significant additional longitudinal data in individual participants.

PROGRESSIVE GAIT DETERIORATION IN ADOLESCENTS WITH DRAVET SYNDROME

Rodda et alArticle characterize changes in gait by age in patients with Dravet syndrome. They indicate that children with Dravet syndrome show progressive gait deterioration in the second decade of life, with crouch gait and skeletal malalignment comprising increased femoral neck anteversion, external tibial torsion, and pes valgus. These age-related changes have a significant impact on mobility and independence in the community setting.

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Crouch gait is characterized by increased hip and knee flexion and ankle dorsiflexion in the sagittal plane throughout the stance phase and is accompanied by bony malalignment in the transverse plane of medial femoral torsion, lateral tibial torsion, and planoabductovalgus of the feet.

CONTRIBUTION OF CEREBROSPINAL FLUID THYMOSIN Β4 LEVELS TO THE CLINICAL DIFFERENTIATION OF CREUTZFELDT-JAKOB DISEASE

Le Pera and colleaguesArticle assess thymosin β4 specificity as relevant to the diagnosis of Creutzfeldt-Jakob disease (CJD). Their findings indicate that cerebrospinal fluid levels of thymosin β4 protein measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry may effectively contribute to discriminate CJD from other forms of dementia.

AGE AND RATE OF COGNITIVE DECLINE IN ALZHEIMER DISEASE: IMPLICATIONS FOR CLINICAL TRIALS

Bernick et alArticle determine the influence of age on Alzheimer disease (AD) course in a clinical trial setting. They report that subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.

PRESERVATION OF NEURONS OF THE NUCLEUS BASALIS IN SUBCORTICAL ISCHEMIC VASCULAR DISEASE

Jung and colleaguesArticle investigate loss of neurons in the nucleus basalis of Meynert in patients with subcortical ischemic vascular disease (SIVD) compared with healthy controls, patients with Alzheimer disease (AD), and patients with mixed AD and SIVD. Their findings inveigh against primary loss of cholinergic neurons in SIVD patients but do not rule out the possibility of secondary cholinergic deficits due to disruptions of cholinergic projections to cerebral cortex.

ALTERATIONS IN BRAIN TRANSITION METALS IN HUNTINGTON DISEASE: AN EVOLVING AND INTRICATE STORY

Rosas et alArticle evaluate and validate the distribution of metal deposition in the brain using advanced magnetic resonance imaging methods from the premanifest through symptomatic stages of Huntington disease (HD). They report that an important and early role of altered metal homeostasis is suggested in the pathogenesis of HD.

EFFECT OF GENETIC VARIATION IN LRRTM3 ON RISK OF ALZHEIMER DISEASE

Reitz and colleaguesArticle explore the role of leucine-rich repeat transmembrane 3 (LRRTM3) in late-onset Alzheimer disease (AD) by independent genetic epidemiologic and functional studies. Their complementary findings support the notions that genetic variation in LRRTM3 is associated with AD risk and that LRRTM3 may modulate γ-secretase processing of amyloid precursor protein.

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Crouch gait is characterized by increased hip and knee flexion and ankle dorsiflexion in the sagittal plane throughout the stance phase and is accompanied by bony malalignment in the transverse plane of medial femoral torsion, lateral tibial torsion, and planoabductovalgus of the feet.

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