阿尔茨海默病生物学标志物研究进展

阿尔茨海默病（AD）是常见的中枢神经系统变性疾病,是痴呆最常见的病因,发病率高.病理特征为老年斑及神经元纤维缠结.AD的确诊有赖病理学,临床诊断极其耗时.由于尚无准确的早期诊断方法,常使AD患者错过早期治疗的时机,这成为制约有效防控AD的瓶颈问题.因此寻找高敏感性、特异性、无创性的生物学标志物对AD的早期诊断至关重要.本文仅将目前较为广泛研究的生物学标志物及其研究现状作一概述.分别对脑脊液、血液、尿液及唾液中的AD标志物作逐一介绍.     

Subjective states associated with retrieval failures in Parkinson’s disease

Instances in which we cannot retrieve information immediately but know that the information might be retrieved later are subjective states that accompany retrieval failure. These are expressed in feeling-of-knowing (FOK) and Tip-of-the-tongue (TOT) experiences. In Experiment 1, participants with Parkinson’s disease (PD) and older adult controls were given general questions and asked to report when they experienced a TOT state and to give related information about the missing word. The PD group experienced similar levels of TOTs but provided less correct peripheral information related to the target when in a TOT state. In Experiment 2, participants were given a Semantic (general knowledge questions) and an Episodic (word pairs) FOK task. PD patients failed to accurately predict their future memory performance (FOK) in response to both episodic and semantic cues. Results are interpreted in the context of recent frameworks of memory and metacognition.     

Sense of identity in advanced Alzheimer’s dementia: A cognitive dissociation between sameness and selfhood?

We looked at whether sense of identity persists in patients with Alzheimer’s disease (AD) and if its profile remains the same between two examinations. A specifically designed protocol was administered to 16 AD patients in the mild to severe stages of dementia and to 16 matched healthy controls, both living in the same institution. We showed that sense of identity was broadly preserved in AD patients. The patterns of their responses were similar to those of controls, and remained consistent over a two-week period. However, some qualitative characteristics of sense of identity in AD patients differed significantly from those of controls, suggesting that AD patients may not be able to update their self-knowledge, probably because of their episodic memory deficit. These results are discussed in the light of both current models of the self and philosophical concepts such as sameness and selfhood.     

Transfer Variables in Tracking Skills

In the present work the effect of two task variables on transfer were studied: shape of the track-circular or triangular; and target speed-constant or variable. One or both of these variables was changed on transfer. Experimental conditions were (a) 10 preshift and 10 post-shift trials, and (b) 20 single-trial alternations of two tasks. 22 groups of 12 Ss each were tested. Condition (a) showed positive transfer with single variable change and zero or negative transfer with simultaneous change in two variables, and condition (b) annulled all transfer effects. Results are discussed in terms of commonality between tasks and receptor and perceptual anticipation.     

Evidence of Incomplete Motor Programming in Parkinson's Disease

One of the essential questions regarding movement deficits in Parkinson's disease (PD) is whether they stem from impaired selecting and switching among movements, impaired use of predictive information to prepare movement, or impaired execution of movement. PD subjects (n = 9) and age-matched control subjects (n = 8) performed a cued, sequential-response RT task. The cue provided either no information, accurate information, or inaccurate information about the upcoming response. PD subjects used predictive information to prepare and to switch among movement sequences normally, but second and third key press latencies were prolonged in comparison with the first key press latency. In Experiments 2 and 3, the effects of choice set and sequence length on key press latencies were examined. These results provide evidence that PD subjects initiate movement before the entire response sequence is prepared. PD does not impair motor programming or execution processes themselves but impairs the smooth coordination of those processes.     

Lower Extremity Kinetics for Balance Control in Children With Cerebral Palsy

The authors examined and compared the effect of support-surface perturbations of various magnitudes on lower extremity kinetics of 7 children with cerebral palsy (CP) and 8 typically developing (TD) children. Results showed that the highest velocity tolerated without stepping was slower in children with CP than in either age-matched TD or younger TD children. Multimodal torque profiles were more frequent in children with CP than in TD controls. TD groups temporally and spatially organized torque activation, whereas children with CP activated all joints simultaneously and showed altered torque contribution patterns among joints. Those results suggest that impairments in reactive postural control in children with CP result not only from developmental delay but also from pathology. Evidence for pathology included increased numbers of torque bursts required to regain stability and less efficient temporal and spatial organization of torque activation patterns.     

Processing Demands During Movement

Subjects made a speeded stylus movement along a track to a stop and simultaneously performed a simple reaction-time task designed to assess the processing demands of the movement task. Movement task variables were: (a) number of alternative ending positions — either one or two — with the choice executed during movement, and (b) presentation time for the endpoint signals in the two-choice conditions, either prior to movement initiation (immediate) or during movement execution (delay). Processing demands were higher during all movement conditions than in a control condition that did not require movement. Processing demands during execution of the one-and two-choice movement with immediate signals did not differ. However, processing demands during the two-choice movements with delayed signals were higher than demands during the two-choice movement with immediate signals.     

Handedness and Hemispheric Asymmetry in the Control Of Movements

This study investigated the influence of hemispheric specialization of function on the motor performance of the hands. Right-handed (n=17), ambidextral (n=21), and ambisinistral (n=12) subjects performed Fitts' (1954) reciprocal tapping task under two conditions with each hand. Conditions had the same index of difficulty but differed in movement precision. The left hand of righthanders was superior in the condition requiring the greatest amount of preprogramming. Conversely, the right hand was not superior in the condition having the greatest demand for feedback control. For ambidextrals, left-hand superiority in the relatively preprogrammed condition was also revealed. Ambisinistrals showed no significant difference between conditions with either hand. The results partially support the hypothesis that the motor performance of the hands mirrors the dominant processing mode of their contralateral hemisphere. Failure to find supportive evidence in ambisinistrals is consistent with the contention that they lack hemispheric specialization of function.     

Bilateral Transfer as a Function of Mental Imagery

Three experiments are reported which investigate the role of mental imagery in the bilateral transfer from right to left hand of rotary pursuit skill. In Experiment 1 both mental imagery and physical rehearsal showed significant positive transfer relative to a control condition. However, work decrement may have accumulated and transferred in the physical rehearsal group thereby depressing this group’s left-hand performance. Experiment 2 was conducted under conditions designed to allow work decrement to dissipate prior to transfer to the contralateral limb. The data still showed no difference between physical re-hearsal and mental imagery. One interpretation of these data is that work decrement was present under both the physical rehearsal and mental imagery manipulations in Experiment 1. The data from Experiment 3 confirmed this interpretation as well as replicated the positive transfer effects found for mental imagery in Experiments 1 and 2. The data are discussed in terms of central versus peripheral explanatory mechanisms.     

Context-Dependent Learning in People With Parkinson's Disease

Context-dependent learning is a phenomenon in which people demonstrate superior performance in the context in which they originally learned a skill but perform less well in a novel context. This study investigated context-dependent learning in people with Parkinson's disease (PD) and age-matched nondisabled adults. All participants practiced 3 finger sequences, each embedded within a unique context (colors and locations on a computer screen). One day after practice, the participants were tested either under the sequence-context associations remained the same as during practice, or the sequence-context associations were changed (SWITCH). Compared with nondisabled adults, people with PD demonstrated significantly greater decrement in performance (especially movement time) under the SWITCH condition, suggesting that individuals with PD are more context dependent than nondisabled adults.