中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

(1998). Human cognitive abilities: A survey of factor analytic studies. Gifted and Talented International: Vol. 13, No. 2, pp. 97-98.

Human cognitive abilities: A survey of factor analytic studies

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Applied Longitudinal Data Analysis Modeling Change And Event Occurrence

Definition: To what extent does the study allow us to draw conclusions about a causal effect between two or more constructs? Issues: Selection, maturation, history, mortality, testing, regression towrd the mean, selection by maturation, treatment by mortality, treatment by testing, measured treatment variables Increase: Eliminate the threats, above all do experimental manipulations, random assignment, and counterbalancing.

Reliability and validity

Mini Mental State

A software package with a modular architecture has been developed to support perceptual modeling of the fine‐grain spectro‐temporal information observed in the auditory nerve. The package contains both functional and physiological modules to simulate auditory spectral analysis, neural encoding, and temporal integration, including new forms of periodicity‐sensitive temporal integration that generate stabilized auditory images. Combinations of the modules enable the user to approximate a wide variety of existing, time‐domain, auditory models. Sequences of auditory images can be replayed to produce cartoons of auditory perceptions that illustrate the dynamic response of the auditory system to everyday sounds.

Time‐domain modeling of peripheral auditory processing: A modular architecture and a software platform

In recent years, there has been a growing interest in the perception of complex sounds, and a growing interest in models that attempt to explain our perception of these sounds in terms of peripheral processes involving the interaction of neighbouring frequency bands and/or more central processes involving the combination of information across distant frequency bands. In this paper we review the perception of four types of complex sound, two traditional (pulse trains and vowels), and two novel (Profile Analysis, PA, and Comodulation Masking Release, CMR). The review is conducted with the aid of a general purpose model of peripheral auditory processing that produces ‘auditory images’ of the sounds. The model includes the interactions associated with adaptation and suppression as observed in the auditory nerve, and it includes the phase alignment and temporal integration which take place before the formation of our initial images of the sounds, but it does not include any of the processes that combine information across widely separated frequency bands. The auditory images assist the discussion of complex sounds by indicating which effects might be explained peripherally and which effects definitely require central processing.

Complex Sounds and Auditory Images

UK Biobank includes 502,649 middle- and older-aged adults from the general population who have undergone detailed phenotypic assessment. The majority of participants completed tests of cognitive functioning, and on average four years later a sub-group of N = 20,346 participants repeated most of the assessment. These measures will be used in a range of future studies of health outcomes in this cohort. The format and content of the cognitive tasks were partly novel. The aim of the present study was to validate and characterize the cognitive data: to describe the inter-correlational structure of the cognitive variables at baseline assessment, and the degree of stability in scores across longitudinal assessment. Baseline cognitive data were used to examine the inter-correlational/factor-structure, using principal components analysis (PCA). We also assessed the degree of stability in cognitive scores in the subsample of participants with repeat data. The different tests of cognitive ability showed significant raw inter-correlations in the expected directions. PCA suggested a one-factor solution (eigenvalue = 1.60), which accounted for around 40% of the variance. Scores showed varying levels of stability across time-points (intraclass correlation range = 0.16 to 0.65). UK Biobank cognitive data has the potential to be a significant resource for researchers looking to investigate predictors and modifiers of cognitive abilities and associated health outcomes in the general population.

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Cognitive Test Scores in UK Biobank: Data Reduction in 480,416 Participants and Longitudinal Stability in 20,346 Participants.

Objective: To determine the magnitude of potentially causal relationships among vascular risk factors (VRFs), large-artery atheromatous disease (LAD), and cerebral white matter hyperintensities (WMH) in 2 prospective cohorts. Methods: We assessed VRFs (history and measured variables), LAD (in carotid, coronary, and leg arteries), and WMH (on structural MRI, visual scores and volume) in: (a) community-dwelling older subjects of the Lothian Birth Cohort 1936, and (b) patients with recent nondisabling stroke. We analyzed correlations, developed structural equation models, and performed mediation analysis to test interrelationships among VRFs, LAD, and WMH. Results: In subjects of the Lothian Birth Cohort 1936 (n = 881, mean age 72.5 years [SD ±0.7 years], 49% with hypertension, 33% with moderate/severe WMH), VRFs explained 70% of the LAD variance but only 1.4% to 2% of WMH variance, of which hypertension explained the most. In stroke patients (n = 257, mean age 74 years [SD ±11.6 years], 61% hypertensive, 43% moderate/severe WMH), VRFs explained only 0.1% of WMH variance. There was no direct association between LAD and WMH in either sample. The results were the same for all WMH measures used. Conclusions: The small effect of VRFs and LAD on WMH suggests that WMH have a large “nonvascular,” nonatheromatous etiology. VRF modification, although important, may be limited in preventing WMH and their stroke and dementia consequences. Investigation of, and interventions against, other suspected small-vessel disease mechanisms should be addressed.

https://n.neurology.org/content/neurology/82/15/1331.full.pdf

Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities

Background Maintaining cognitive function is an important aspect of healthy ageing. In this study, we examined age trajectories of cognitive decline in a large nationally representative sample of older people in England. We explored the factors that influence such decline and whether these differed by gender. Methods Latent growth curve modelling was used to explore age-specific changes, and influences on them, in an 8-year period in memory, executive function, processing speed and global cognitive function among 10 626 participants in the English Longitudinal Study of Ageing. We run gender-specific models with the following exposures: age, education, wealth, childhood socioeconomic status, cardiovascular disease, diabetes, physical function, body mass index, physical activity, alcohol, smoking, depression and dementia. Results After adjustment, women had significantly less decline than men in memory (0.011, SE 0.006), executive function (0.012, SE 0.006) and global cognitive function (0.016, SE 0.004). Increasing age and dementia predicted faster rates of decline in all cognitive function domains. Depression and alcohol consumption predicted decline in some cognitive function domains in men only. Poor physical function, physical inactivity and smoking were associated with faster rates of decline in specific cognitive domains in both men and women. For example, relative to study members who were physically active, the sedentary experienced greater declines in memory (women −0.018, SE 0.009) and global cognitive function (men −0.015, SE 0.007 and women −0.016, SE 0.007). Conclusions The potential determinants of cognitive decline identified in this study, in particular modifiable risk factors, should be tested in the context of randomised controlled trials.

https://jech.bmj.com/content/jech/72/8/685.full.pdf

Michael Allerhand

Papers

Time‐domain modeling of peripheral auditory processing: A modular architecture and a software platform

Complex Sounds and Auditory Images

Cognitive Test Scores in UK Biobank: Data Reduction in 480,416 Participants and Longitudinal Stability in 20,346 Participants.

Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities

Cognitive function trajectories and their determinants in older people: 8 years of follow-up in the English Longitudinal Study of Ageing