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This Month in Archives of Neurology
December 2009

This Month in Archives of Neurology

Arch Neurol. 2009;66(12):1442-1444. doi:10.1001/archneurol.2009.274
Mild Cognitive Impairment: 10 Years Later

Petersen and colleaguesArticle in this review summarize the progress that has been made, while recognizing the challenges that remain, in defining mild cognitive impairment. In the past 10 years, there has been a virtual explosion in the literature concerning the construct of mild cognitive impairment. The interest in this topic demonstrates the increasing emphasis on the identification of the earliest features of cognitive disorders such as Alzheimer disease and other dementias. Mild cognitive impairment represents the earliest clinical features of these conditions and, hence, has become a focus of clinical, epidemiological, neuroimaging, biomarker, neuropathological, disease mechanism, and clinical trials research.

Hypothetical temporal ordering of neuropathological processes in the course of Alzheimer disease and corresponding imaging and biomarker measures. Aβ indicates amyloid β; CSF, cerebrospinal fluid; 18FDG PET, fludeoxyglucose F 18–positron emission tomography; MCI, mild cognitive impairment; and MRI, magnetic resonance imaging.

Hypothetical temporal ordering of neuropathological processes in the course of Alzheimer disease and corresponding imaging and biomarker measures. Aβ indicates amyloid β; CSF, cerebrospinal fluid; 18FDG PET, fludeoxyglucose F 18–positron emission tomography; MCI, mild cognitive impairment; and MRI, magnetic resonance imaging.

Cellular Mechanisms of Central Nervous System Repair by Natural Autoreactive Monoclonal Antibodies

Wright and colleaguesArticle describe current research related to natural autoreactive monoclonal IgMs that have demonstrated potential as therapeutic agents for central nervous system disease. These antibodies bind surface antigens on specific central nervous system cells, activating intracellular repair-promoting signals. The IgMs that bind to surface antigens on oligodendrocytes enhanced remyelination in animal models of multiple sclerosis. The IgMs that bind to neurons stimulate neurite outgrowth and prevent neuron apoptosis. Neuron-binding IgMs may have utility in central nervous system axon- or neuron-damaging diseases such as amyotrophic lateral sclerosis, stroke, spinal cord injury, or secondary progressive multiple sclerosis.

Urate Predicts Rate of Clinical Decline in Parkinson Disease

Ascherio et alArticle report that higher serum and cerebrospinal fluid urate levels at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate and Parkinson disease and the rationale for considering central nervous system urate elevation as a potential strategy to slow Parkinson disease progression. Editorial perspective is provided by George Perry, PhD, et al.Article

Pittsburgh Compound B Imaging and Prediction of Progression From Cognitive Normality to Symptomatic Alzheimer Disease

Morris and colleaguesArticle have studied whether preclinical Alzheimer disease (AD), as detected by the amyloid imaging agent Pittsburgh Compound B (PiB) in cognitively normal older adults, is associated with risk of symptomatic AD. A longitudinal cohort study of cognitively normal older adults was assessed with positron emission tomography to determine the mean cortical binding potential for PiB and was followed up with annual clinical and cognitive assessments for progression to very mild dementia of the Alzheimer type. Preclinical AD, as detected by positron emission tomography PiB, is not benign, as it is associated with progression to symptomatic AD.

Cognitive Decline and Brain Volume Loss as Signatures of Cerebral Amyloid-β Peptide Deposition Identified With Pittsburgh Compound B

Storandt et alArticle have examined the relation of amyloid-β levels in the cerebral cortex with structural brain integrity and cognitive performance in older people with a Clinical Dementia Rating of 0 (cognitively normal). They report that carbon 11–labeled Pittsburgh Compound B, an in vivo measure of cerebral amyloidosis, is associated with regionally specific brain atrophy cross-sectionally as well as a pattern of longitudinal cognitive decline in multiple cognitive domains that occurs prior to the clinical diagnosis of Alzheimer disease. Their findings contribute to the understanding of the cognitive and structural consequences of amyloid-β levels in older adults with a Clinical Dementia Rating of 0.

Transactive Response DNA-Binding Protein 43 Burden in Familial Alzheimer Disease and Down Syndrome

Lippa and colleaguesArticle point out that transactive response DNA-binding protein 43 (TDP-43) has been described in neuronal and glial inclusions characteristic of primary TDP-43 proteinopathies including amyotrophic lateral sclerosis and some forms of frontotemporal dementia. However, they indicate that similar TDP-43 pathologies also have been described in secondary TDP-43 proteinopathies such as Alzheimer disease (AD) and age-associated cognitive impairment in which the burden of TDP-43 lesions correlates with the degree of cognitive loss. They have assessed TDP-43 burden in familial forms of AD and Down syndrome to determine whether TDP-43 inclusions are also present. They report that TDP-43 pathology occurs in familial AD and Down syndrome similar to that observed in sporadic AD. Thus, pathological TDP-43 may contribute the cognitive impairment in familial and sporadic forms of AD.

Surgical Outcome of Patients With Refractory Magnetic Resonance Imaging–Negative Epilepsies

Bien et alArticle indicate that patients with pharmacoresistant epilepsy without distinct magnetic resonance imaging lesions (MRI) account for a relevant proportion of presurgical patient cohorts. They report that patients with MRI epilepsy can be successfully treated with surgery. Improved sensitivity of MRI will improve outcome of presurgically studied patients. Surgical failures in patients without histopathological lesions mostly result from extensive epileptogenic areas.

Status Epilepticus Associated With Subtentorial Posterior Fossa Lesions

Grill and TreimanArticle have examined the prevalence, clinical features, potential risk factors, and outcomes of status epilepticus among patients presenting with subtentorial posterior fossa lesions. They report that status epilepticus can be a potential complication in patients with posterior fossa cranial lesions and can be seen in up to 2.6% of such patients. Most have an unfavorable outcome.

Functional and Cognitive Outcome in Prolonged Refractory Status Epilepticus

Cooper et alArticle have determined the functional and cognitive outcomes of patients with prolonged refractory status epilepticus lasting 7 or more days despite the use of anesthetic agents for seizure suppression. They find that, despite the high mortality rate, survival with meaningful functional and cognitive recovery is possible after prolonged refractory status epilepticus. Prolonged duration of status epilepticus alone should not be considered a reason to discontinue treatment.

Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Type 2 Caused by Mitofusin 2 Mutations

Calvo and colleaguesArticle describe mutations in the gene encoding mitofusin 2 (MFN2) and associated phenotypes in a sample of patients with hereditary motor and sensory neuropathy. They report that MFN2 mutations are a frequent cause of Charcot-Marie-Tooth disease type 2 with variable severity and either dominant or recessive inheritance. MFN2 gene testing must be a first-line analysis in axonal hereditary motor and sensory neuropathy irrespective of the mode of inheritance or severity of the peripheral neuropathy.

Motor Phenotype of LRRK2 G2019S Carriers in Early-Onset Parkinson Disease

Alcalay and colleaguesArticle determined the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor-dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability gait difficulty phenotype. They report that G2019S LRRK2 carriers with early-onset Parkinson disease are more likely to manifest the postural instability gait difficulty phenotype, which may have implications for disease course.

Heterogeneity in Infarct Patterns and Clinical Outcome Following Internal Carotid Artery Occlusion

Phan et alArticle have hypothesized that the extent of infarction and clinical outcome after internal carotid artery occlusion depends on the additional occlusion of the middle cerebral artery (MCA). They show that patients with internal carotid artery occlusion but without coexistent MCA occlusion have different infarct patterns, less extensive infarcts, and better clinical outcomes than those with coexistent MCA occlusion or MCA occlusion alone. Such patients may not warrant exclusion from acute stroke trials.

HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis

Sombekke et alArticle hypothesize that in multiple sclerosis variation in lesion location between brain and spinal cord might be (partially) genetically determined. They find that carriers of HLA-DRB1*1501 had a median of 4 spinal cord lesions compared with 2 lesions for noncarriers (P < .001). No significant association was present between the single-nucleotide polymorphisms and T2 lesion load in the brain.

High Striatal Amyloid-β Deposition Across Different Autosomal Alzheimer Disease Mutation Types

Villemagne and colleaguesArticle report, consistent with previous reports, that familial Alzheimer disease presents a different pattern of amyloid-β deposition than sporadic Alzheimer disease, with higher striatal and somewhat lower cortical Pittsburgh Compound B retention. The pattern and degree of amyloid-β deposition was not associated with mutation type nor with cognitive status.

Quantitative Template for Subtyping Primary Progressive Aphasia

Mesulam and colleaguesArticle have provided a quantitative algorithm for classifying primary progressive aphasia (PPA) into agrammatic, semantic, and logopenic variants, each of which is known to have a different probability of association with Alzheimer disease vs frontotemporal lobar degeneration. They indicate that once an accurate root diagnosis of PPA is made, subtyping can be quantitatively guided using a 2-dimensional template based on orthogonal tasks of grammatical competence and word comprehension.

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