Objectives: To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia.

Design: Validation study.

Setting: A community clinic and an academic center.

Participants: Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score≥17), and 90 healthy elderly controls (NC).

Measurements: The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD.

Results: Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively).

Conclusion: MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.

/pdf/the-montreal-cognitive-assessment-moca-a-brief-screening-4w06t9e7qy.pdf

The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

/pdf/the-diagnosis-of-dementia-due-to-alzheimer-s-disease-w5k0egjbz5.pdf

The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease

Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.

Neuropathological stageing of Alzheimer-related changes.

Background Subjects with a mild cognitive impairment (MCI) have a memory impairment beyond that expected for age and education yet are not demented. These subjects are becoming the focus of many prediction studies and early intervention trials. Objective To characterize clinically subjects with MCI cross-sectionally and longitudinally. Design A prospective, longitudinal inception cohort. Setting General community clinic. Participants A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn. Main Outcome Measures The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination, Wechsler Adult Intelligence Scale–Revised, Wechsler Memory Scale–Revised, Dementia Rating Scale, Free and Cued Selective Reminding Test, and Auditory Verbal Learning Test. Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, respectively. Results The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable. However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well. Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD. Conclusions Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD. They appear to constitute a clinical entity that can be characterized for treatment interventions.

/pdf/mild-cognitive-impairment-clinical-characterization-and-294aut8v7m.pdf

Mild Cognitive Impairment: Clinical Characterization and Outcome

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Tetanus toxin: evidence for binding at presynaptic nerve endings

Biochemical and genetic abnormalities of alpha-synuclein (alpha-Syn) are implicated in the pathogenesis of Parkinson's disease (PD) and other alpha-synucleinopathies. The abnormal intraneuronal accumulations of alpha-Syn in Lewy bodies (LBs) and Lewy neurites (LNs) have implicated defects in axonal transport of alpha-Syn in the alpha-synucleinopathies. Using human (Hu) alpha-Syn transgenic (Tg) mice, we have examined whether familial PD (FPD)-linked mutations (A30P and A53T) alter axonal transport of Hualpha-Syn. Our studies using peripheral nerves show that Hualpha-Syn and Moalpha-Syn are almost exclusively transported in the slow component (SC) of axonal transport and that the FPD-linked alpha-Syn mutations do not have obvious effects on the axonal transport of alpha-Syn. Moreover, older pre-symptomatic A53T Hualpha-Syn Tg mice do not show gross alterations in the axonal transport of alpha-Syn and other proteins in the SC, indicating that the early stages of alpha-synucleinopathy in A53T alpha-Syn Tg mice are not associated with gross alterations in the slow axonal transport. However, the axonal transport of alpha-Syn slows significantly with aging. Because the rate of axonal transport affects the stability and accumulation of proteins in axons, age-dependent-slowing alpha-Syn is a likely contributor to axonal aggregation of alpha-Syn in alpha-synucleinopathy.

Axonal transport of human α‐synuclein slows with aging but is not affected by familial Parkinson's disease‐linked mutations

Alzheimer disease and the prion disorders/spongiform encephalopathies share many common features. These chronic, progressive, sometimes familial diseases of the central nervous system are characterized by the presence of different types of amyloid deposits in the brain. This review provides a perspective on these two types of neurodegenerative disorders.

Donald L. Price

Papers

Tetanus toxin: evidence for binding at presynaptic nerve endings

Axonal transport of human α‐synuclein slows with aging but is not affected by familial Parkinson's disease‐linked mutations

Alzheimer disease and the prion disorders amyloid beta-protein and prion protein amyloidoses.

Age-associated inclusions in normal and transgenic mouse brain

Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APPSWE