Introduction 2002 2006 2005 2006 2004 2005 2006 2002 2006 2003 2001 2003 explicit declarative 2004 2001 2002 implicit procedural 1998 2000 Materials and Methods Computerized searches of the literature using the databases of PubMed and PsycLIT were conducted spanning a 20-year period, from 1985 up to and including 2005. The search terms (any field) used were procedural learning, sequence learning, motor-skill learning, or motor learning in combination with Alzheimer’s disease. Only reports published in English were considered. For inclusion in this review the studies had to meet the following criteria: (a) a clinical diagnosis of Alzheimer’s disease based on specified and generally accepted criteria; (b) a procedural task with motor responses; and (c) task performance expressed in time or error measures, and not only in fMRI or other imaging data. Ultimately, 23 studies were included in this review. Three studies will only be discussed in the second part of the review since they explicitly examined the role of feedback and type of practice. Experimental Research of Implicit Motor-Skill Learning in Alzheimer’s Disease Implicit Learning Ability 1 1999 1995 1997 1998 1995 1994 1995 2001 1988 1989 1999 1998 1997 1997 2002 1990 1987 1991 1997 1997 1991 1993 Table 1 Summary of results of experimental studies on motor-skill learning in Alzheimer’s disease Author Year Sample size and types Task(s) a Results on learning capacity Sabe, L., et al. 1995 20 AD with co-morbid depression, 35 AD without co-morbid depression, 14 depressive, non-demented patients, 16 healthy controls Maze test AD: 19%Co: 22% The AD patients showed significant deficits in declarative learning but only a minor (although statistically significantly) drop in procedural learning. The AD group with comorbid depression showed a similar learning pattern as the non-depressed AD group. p Starkstein, S.E., et al. 1997 55 AD (13 with mild, 12 with severe and 30 without anosognosia) Maze test AD no: 48% There was no group difference in declarative learning. As to procedural learning, the patients with severe anosognosia showed a significantly poorer performance whereas the patients with mild or no anosognosia showed no deficits. AD mild: 39% AD severe: −16% – Taylor, R. 1998 58 AD, 58 multi-infarct dementia Maze test – When age and overall neuropsychological functioning were taken into account, Maze performance was better in the AD patients than in the patients with multi-infarct dementia – Kuzis, G., et al. 1999 15 AD, 15 PD, 10 PD and dementia, 24 healthy controls Maze test AD: 10% The AD group showed deficits on all measures of explicit memory. There were no significant between-group differences in the measures of implicit memory between the AD, control, and PD groups. Co: 39% – Heidel, W.C., et al. 1988 10 AD, 10 HD, 4 amnestic 20 healthy controls t AD: 147% The AD patients showed preserved motor-skill learning while the patients with HD showed no motor learning. Co: 115% GroupxTrial: n.s. Heindel, W.C. et al. 1989 16 AD, 13 HD, 17 PD, 22 healthy controls Rotor Pursuit AD: 101% The AD patients showed preserved motor-skill learning while the patients with HD showed impaired motor learning. Co: 118% GroupxTrial: n.s. Beatty, W.W., et al. 1995 4 AD, 1 corticbasal degeneration Rotor Pursuit – The AD patients showed preserved motor skill learning – Deweer, B., et al. 1994 13 AD institutionalized, 10 healthy controls, 17 AD out patients, 9 healthy controls Rotor Pursuit AD in.:86% Explicit memory was severely impaired in the AD patients but they showed normal procedural learning. Co: 48% GroupxTrial: n.s. AD out: 161% Co: 139% GroupxTrial: n.s. Dick, M.B., et al. 1995 12 AD, 12 healthy controls Rotor Pursuit AD: 47% Performance significantly improved during the first 40 trials but additional practice provided no further beneficial effects. The AD patients showed minimal retention problems across four retention tests. Co: 81% GroupxTrial: n.s. Libon, D.J., et al. 1998 16 AD, 14 vascular dementia Rotor Pursuit AD: 60% The AD patients obtained a lower score on a verbal-learning task-recognition index and high scores on the Rotor Pursuit. – Jacobs, D.H., et al. 1999 12 AD, 12 healthy controls Rotor Pursuit AD: 124% The AD patients and the controls were able to learn the motor task. Co: 106% p Dick, M.B., et al. 2001 18 AD, 18 healthy controls Rotor Pursuit AD: 27% In normal-vision trials no differences in learning between the AD patients and the controls were found. Co: 36% GroupxTrial: n.s. Dick, M.B., et al. 2003 99 AD, 100 healthy controls Rotor Pursuit  The AD patients and controls receiving constant practice outperformed those in the blocked and random conditions. The AD patients only benefited from constant practice. Poe, M.K. et al. 1997 9 AD, 14 healthy controls Puzzle Assembly – Even when the subjects had no explicit memory of practicing the task, they all demonstrated savings upon relearning.   GroupxTrial: n.s. Rouleau, I., et al. 2002 12 AD, 12 healthy controls Mirror Tracing AD: 44% Those AD patients that were able to perform the basic mirror-tracing task did not differ from the controls in level of performance, learning over trails, retention over a delay interval and generalization to other tasks Co: 49% GroupxTrial: n.s. Knopman, D.S., et al. 1987 35 AD, 13 healthy controls SRTT AD: 22% The AD patients showed learning of the repeated sequence, although they responded more slowly. Co: 38% GroupxTrial: n.s. Graftman, J., et al. 1990 42 AD, 7 PSP, 44 healthy controls SRTT AD: 36% The AD patients and controls showed motor-skill learning while the PSP patients did not. – Knopman, D. 1991 16 AD, 17 healthy controls SRTT AD: 37% The AD patients showed learning of the sequence but they showed an inferior level of learning when the data were log-transformed. Co: 33% Ferraro, F.R., et al. 1993 27 very mild AD, 15 mild AD, 17 PD, 26 healthy controls SRTT AD mild: 11% The very mildly AD patients showed preserved learning comparable with the controls. The mildly AD patients and PD patients showed less implicit learning. AD very mild: 22% Co: 20% Willingham, D.B., et al. 1997 20 AD, 20 healthy controls SRTT, Incompatible SRTT, Pursuit Tracking (randomized and repetitive pattern) SRTT: The dementia ratings predicted the ability to perform tasks but not the ability to learn them. AD patients can have a performance deficit but they have no general deficit in motor-skill learning. AD: 52% Co: 60% GroupXTrial: p > 0.2 Pursuit: AD: 12% Co: 17% GroupxTrial: p > 0.2 Hirono, N., et al. 1997 36 AD, 19 healthy controls Bi-manual coordinated Tracing task AD: 37% Skill learning in those AD patients that completed the tasks was as good as in the controls.   Co: 39%  p Dick, M.B., et al. 1996 23 AD, 22 healthy controls Tossing  The AD patients given constant practice were able to learn and retain the tossing task similarly well as the controls. The AD patients showed less improvement when practicing at various distances. Dick, M.B., et al. 2006 58 AD, 58 healthy controls Tossing  The AD patients showed significant improvements under constant practice only. None of the practice conditions facilitated intermediate transfer in the AD patients whereas constant practice did benefit them on tests assessing near transfer. AD HD PD PSP a Thus, irrespective of the task used, the studies assessing implicit motor-skill learning in AD we reviewed yielded positive outcomes. Indeed, in their 1997 study, Hirono and colleagues found that patients with mild AD were able to acquire motor and perceptual as well as cognitive skills in various procedural learning tasks. 1997 Performance and Amount of Learning 1997 1995 1990 1998 1997 1998 1993 1987 1991 1997 1994 1995 2001 1988 1989 1997 1999 2002 1997 1999 1995 1996 Training Patients with Alzheimer’s Disease: Variables in Motor Learning practice feedback 1967 1998 1999 Practice: Theory and Outcome Studies with AD Patients 1995 1999 1995 2000 1988 2000 1988 1996 2000 2003 1996 2003 1975 2003 1996 2003 1988 1995 1993 1988 Feedback: Theory and Outcome Studies with AD Patients 2000 1988 1995 1988 1995 1999 1994 1995 1999 1998 2001 It can be tentatively concluded that for AD patients, constant visual feedback is important in learning motor skills, but more research is needed to confirm this hypothesis. We did not find any studies that were concerned with the frequency of external feedback, and whether knowledge of results and knowledge of performance makes a difference in this patient group. Based on the results cited above, it may be hypothesized that both forms of feedback knowledge probably place too much weight on the cognitive abilities in AD patients and therefore contribute little to successful performance. Conclusions and Recommendations People with Alzheimer’s disease are able to implicitly (re)learn motor skills to a certain extent and under specific conditions. The experimental research to date shows preserved implicit motor learning irrespective of the task used. Patients are capable of acquiring motor skills without awareness simply by repeated exposure, although their performances will not reach normal levels. This is expressed in their protracted performance relative to that of unimpaired controls. Moreover, extent of learning will differ depending on the task to be mastered. 2003 1993 The studies we reviewed showed that in (re)learning motor skills, constant, or rather frequent and consistent practice is important in AD patients. This way of learning draws less on episodic memory and other cognitive functions compromised in AD patients. These data also suggest that practice under dual-task conditions should also be avoided. Because AD patients have difficulty in generalizing the motor skills learned during the sessions, training has to take place in an environment that closely resembles the one in which the skill is going to be used and presumably with tools used by the AD patient in his or her daily life. If, for instance, an AD patient is trained in the use of a microwave, the device used during the training should be the same as the one available in the patient’s household. The amount of training a patient needs will depend on the task being trained. The role of fatigue is also important in this respect. The effects of massed and distributed practice in this generally older patient group need to be addressed in future investigations. 2004 In the introduction of our review we asked whether patients with Alzheimer’s disease might have intact motor-skill learning abilities. The answer is twofold. Clearly, AD patients show preserved implicit learning abilities that can be utilized in teaching (motor) skills, yet transfer to other skills is minimal. Accordingly, the professionals delivering the training programs should tailor the contents to the particular needs and abilities of this patient group or the individual patient. When the above guidelines are kept in mind and when our knowledge on this topic are widened, non-pharmacological interventions might contribute significantly in helping elderly people suffering from dementia to keep their autonomy. The extent to which pharmacological intervention may enhance these behavioral mechanisms and foster independent living in AD patients has yet to be determined.