Alzheimer Disease: Scherder EJ

van Halteren-van Tilborg IA, Scherder EJ, Hulstijn W. · Elkerliek Hospital, P.O. Box 98, 5700 AB, Helmond, The Netherlands. · Neuropsychol Rev. · Pubmed #17680369 links to  free full text

Abstract: Since elderly people suffering from dementia want to go on living independently for as long as possible, they need to be able to maintain familiar and learn new practical skills. Although explicit or declarative learning methods are mostly used to train new skills, it is hypothesized that implicit or procedural techniques may be more effective in this population. The present review discusses 23 experimental studies on implicit motor-skill learning in patients with Alzheimer's disease (AD). All studies found intact implicit motor-learning capacities. Subsequently, it is elaborated how these intact learning abilities can be exploited in the patients' rehabilitation with respect to the variables 'practice' and 'feedback.' Recommendations for future research are provided, and it is concluded that if training programs are adjusted to specific needs and abilities, older people with AD are well able to (re)learn practical motor skills, which may enhance their autonomy.

Scherder EJ, Luijpen MW, van Dijk KR. · Department of Clinical Neuropsychology, Vrije Universiteit, Van der Boechorststraat 1, 1081 BTAmsterdam, The Netherlands. · Chin J Physiol. · Pubmed #15074834 No free full text.

Abstract: In 1990 a series of studies started in which the effects of Transcutaneous Electrical Nerve Stimulation (TENS) was examined on cognition, behaviour, and the rest-activity rhythm of patients with Alzheimer's disease (AD). In these studies, TENS aimed primarily at stimulating the dorsal raphe nucleus (DRN) and the locus coeruleus (LC) by a combination of low- and high-frequency stimulation (2 Hz and 160 Hz, respectively), a pulse width of 0.1 ms, and an intensity that provokes muscular twitches. TENS was applied 30 min a day, during a six-week period. In order to make reliable comparisons between studies, identical stimulation-parameters were used in all studies thus far. TENS appeared to have a positive effect on cognition, behaviour, and the rest-activity rhythm but the effects disappeared after cessation of stimulation. In order to optimise TENS treatment in AD, the present paper is meant to reconsider the once selected stimulation-parameters by reviewing the relevant literature published since 1991. The results derived from animal experimental studies show that for an optimal stimulation of the LC and DRN, the pulse width should be more than 0.1 ms. Limitations and suggestions for future research will be discussed.

Swaab DF, Dubelaar EJ, Scherder EJ, van Someren EJ, Verwer RW. · Netherlands Institute for Brain Research, Amsterdam, The Netherlands. · Alzheimer Dis Assoc Disord. · Pubmed #14512817 No free full text.

Abstract: Based on several lines of evidence, it has been hypothesized that decreased neuronal metabolic rate may precede cognitive impairment, contributing to neuronal atrophy as well as reduced neuronal function in Alzheimer disease (AD). Additionally, studies have shown that stimulation of neurons through different mechanisms may protect those cells from the deleterious effects of aging and AD, a phenomenon we paraphrased as "use it or lose it." Therefore, it is attractive to direct the development of therapeutic strategies toward stimulation of metabolic rate/neuronal activity to improve cognition and other symptoms in AD. A number of pharmacological and nonpharmacological approaches discussed here support the concept that stimulation of the brain has beneficial effects and may, to a certain degree, restore several aspects of cognition and other central functions. For instance, the circadian system, which controls the sleep/wake cycle, may be stimulated in AD patients by exposing them to more light or transcutaneous nerve stimulation. We will also discuss a procedure that has been developed to culture human postmortem brain tissue, which allows testing of the efficacy of putative stimulatory compounds.

Swaab DF, Dubelaar EJ, Hofman MA, Scherder EJ, van Someren EJ, Verwer RW. · Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands. · Prog Brain Res. · Pubmed #12432778 No free full text.

Abstract: (1) Alzheimer's disease is a multifactorial disease in which age and APOE-epsilon 4 are important risk factors. (2) The neuropathological hallmarks of AD, i.e. amorphous plaques, neuritic plaques (NPs), pretangles, neurofibrillary tangles (NFT) and cell death are not part of a single pathogenetic cascade but may occur independently. (3) In brain areas where classical AD changes, i.e. NPs and NFTs, are present, such as the CA1 area of the hippocampus, the nucleus basalis of Meynert and the tuberomamillary nucleus, a decreased metabolic rate is found. The decreased metabolic rate appears not to be induced by the presence of pretangles, NFT or NPs. (4) Decreased metabolic rate may precede cognitive impairment and is thus an early occurring hallmark of AD, which, in principle, may be reversible. The observation that the administration of glucose or insulin enhances memory in AD patients also supports the view that AD has a metabolic basis. (5) Moreover, several observations in postmortem brain indicate that activated neurons are better able to withstand aging and AD, a phenomenon paraphrased by us as 'use it or lose it'. (6) It is, therefore, attractive to direct the development of therapeutic strategies towards restimulation of neuronal metabolic rate in order to improve cognition and other symptoms in AD. A number of pharmacological and non-pharmacological studies support the concept that activation of the brain has beneficial effects and may, to a certain degree, restore several aspects of cognition and other central functions. For instance, the circadian system may be restimulated in AD patients by exposing them to more light or transcutaneous nerve stimulation. A procedure has been developed to culture human postmortem brain tissue that allows testing of the efficacy of putative stimulatory compounds such as neurotrophins.

van Dijk KR, Scherder EJ, Scheltens P, Sergeant JA. · Department of Clinical Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands. · Rev Neurosci. · Pubmed #12405228 No free full text.

Abstract: An extensive search through nine electronic bibliographic databases (PubMed, Cochrane Library, Web of Science, ERIC, PsychINFO, Psyndex, Cinahl, Biological Abstracts, Rehabdata) was performed in order to review the effects of Transcutaneous Electrical Nerve Stimulation (TENS) on non-pain related cognitive and behavioural functioning. Eight studies were identified on neglect due to stroke, six studies on Alzheimer's disease (AD), one study on aging, and two studies on coma due to traumatic brain injury. The results of the various studies revealed that TENS has a variety of effects. These consist of enhancement of somatosensory functioning, visuo-spatial abilities and postural control in neglect, improved memory, affective behaviour and rest-activity rhythm in AD and acceleration of awakening in coma. Effectiveness of TENS is discussed in relation to various stimulation parameters: duration, frequency, pulse width and intensity. It is argued that arousal may underlie the beneficial influence of TENS in various conditions. Finally, suggestions are offered for future research.

Scherder EJ. · Department of Clinical Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands. · Psychiatry. · Pubmed #10855753 No free full text.

Abstract: This article discusses three possible mechanisms that might underlie the often observed low use of nonsteroidal anti-inflammatory drugs (NSAIDs) and other analgesics in patients with Alzheimer's disease (AD), compared with nondemented elderly: (a) AD patients are progressively less able to communicate about pain; (b) AD patients suffer from fewer painful conditions than nondemented elderly subjects; and (c) considering the neuropathology, AD patients might actually experience pain to a lesser extent. Suggestions for future pain assessment in AD are made.

van Dijk KR, Scheltens P, Luijpen MW, Sergeant JA, Scherder EJ. · Department of Clinical Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands. · Dement Geriatr Cogn Disord. · Pubmed #15802911 No free full text.

Abstract: In a number of studies, peripheral electrical nerve stimulation has been applied to Alzheimer's disease (AD) patients who lived in a nursing home. Improvements were observed in memory, verbal fluency, affective behavior, activities of daily living and on the rest-activity rhythm and pupillary light reflex. The aim of the present, randomized, placebo-controlled, parallel-group clinical trial was to examine the effects of electrical stimulation on cognition and behavior in AD patients who still live at home. Repeated measures analyses of variance revealed no effects of the intervention in the verum group (n = 32) compared with the placebo group (n = 30) on any of the cognitive and behavioral outcome measures. However, the majority of the patients and the caregivers evaluated the treatment procedure positively, and applying the daily treatment at home caused minimal burden. The lack of treatment effects calls for reconsideration of electrical stimulation as a symptomatic treatment in AD.

Scherder EJ, Deijen JB, Vreeswijk SH, Sergeant JA, Swaab DF. · Department of Clinical Neuropsychology, Vrije Universiteit, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. · Behav Brain Res. · Pubmed #11796166 No free full text.

Abstract: In one study, behavioral disorders of patients with vascular dementia reacted positively to cranial electrostimulation (CES). In the present study, it was examined whether CES could improve cognition and (affective) behavior in patients with probable Alzheimer's disease (AD). Eighteen AD patients, divided into an experimental and a placebo group, were treated for 30 min per day, 5 days a week, for 6 weeks. No improvements in cognition and (affective) behavior were found after CES.

Scherder EJ, Van Someren EJ, Bouma A, v d Berg M. · Department of Clinical Neuropsychology, Vrije Universiteit, De Boelelaan 1109, 1081 HV, Amsterdam, The Netherlands. · Behav Brain Res. · Pubmed #10840147 No free full text.

Abstract: In previous studies, transcutaneous electrical nerve stimulation (TENS) improved cognition and behaviour in patients with Alzheimer's disease (AD). The rationale underlying these studies was that TENS could activate, e.g. the septo-hippocampal region and the hypothalamus through direct and indirect pathways. As these areas are also affected in normal aging, the present study examined the effects of TENS on cognition and behaviour in nondemented elderly persons. The results suggest an improvement in visual short-term and verbal long-term (recognition) memory, and semantic verbal fluency. Moreover, stimulated elderly persons felt less depressed. Limitations are discussed.

Scherder EJ, Van Someren EJ, Swaab DF. · Free University, Department of Clinical Psychology, Amsterdam, The Netherlands. · Behav Brain Res. · Pubmed #10342404 No free full text.

Abstract: Nightly restlessness in patients with Alzheimer's disease (AD) is probably due to a disorder of circadian rhythms. Transcutaneous electrical nerve stimulation (TENS) was previously reported to increase the strength of coupling of the circadian rest activity rhythm to Zeitgebers in early stage Alzheimer's disease (AD) patients. It was investigated in the present study whether TENS could also improve the rest activity rhythm of patients in a midstage. Sixteen patients who met the NINCDS ADRDA criteria for probable AD, and the stage 6 criteria of the Global Deterioration Scale were treated with TENS or placebo. Rest activity rhythm was assessed using actigraphy. Compared to the control group, stimulated patients showed an improvement in the rest activity rhythm of similar magnitude as observed previously in patients in an early stage. It is concluded that TENS increased the coupling between the rest activity rhythm and supposedly stable Zeitgebers in an advanced stage of AD.

Scherder EJ, Bouma A. · Department of Clinical Psychology, Vrije Universiteit, Amsterdam, The Netherlands. · Biol Psychiatry. · Pubmed #10188004 No free full text.

Abstract: BACKGROUND: In previous studies, transcutaneous electrical nerve stimulation (TENS) was shown to result in improvements in nonverbal short-term and long-term memory, verbal long-term memory, and verbal fluency in patients in an early stage of Alzheimer's disease (AD). In addition, the patients' physical, social, and affective functioning improved. As AD is a progressive disease, it was examined in the present study whether TENS would still be effective in the midstage of AD. METHODS: Sixteen subjects (70-91 years old) met the NINCDS-ADRDA criteria for probable AD, as well as the criteria for stage 6 of the Global Deterioration Scale (midstage AD). To evaluate treatment effects, the subjects underwent a number of neuropsychological tests and two observation scales. RESULTS: Compared to TENS in an early stage, TENS in the midstage of AD appears to yield less beneficial effects, i.e., as for cognition only nonverbal short-term memory improved. No treatment effects were observed for the patients' physical, social, and affective functioning. CONCLUSIONS: In view of the small number of patients, the clinical relevance of TENS in patients in a midstage of AD remains to be confirmed in a larger group, after which more definite conclusions about the stage-dependency of TENS in AD can be drawn.

Oosterman JM, van Someren EJ, Vogels RL, Van Harten B, Scherder EJ. · Experimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, The Netherlands. · J Sleep Res. · Pubmed #19250179 No free full text.

Abstract: Aging affects both cognitive performance and the sleep-wake rhythm. The recent surge of studies that support a role of sleep for cognitive performance in healthy young adults suggests that disturbed sleep-wake rhythms may contribute to 'age-related' cognitive decline. This relationship has however not previously been extensively investigated. The present correlational study integrated a battery of standardized cognitive tests to investigate the association of mental speed, memory, and executive function with actigraphically recorded sleep-wake rhythms in 144 home-dwelling elderly participants aged 69.5 +/- 8.5 (mean +/- SD). Multiple regression analyses showed that the partial correlations of the fragmentation of the sleep-wake rhythm with each of the three cognitive domains (r = -0.16, -0.19, and -0.16 respectively) were significant. These associations were independent from main effects of age, implying that a unique relationship between the rest-activity rhythm and cognitive performance is present in elderly people.

Scherder EJ, Eggermont L, Plooij B, Oudshoorn J, Vuijk PJ, Pickering G, Lautenbacher S, Achterberg W, Oosterman J. · Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands. · Gerontology. · Pubmed #18185014 links to  free full text

Abstract: BACKGROUND: Brain areas that are involved in cognition and mood also play a role in pain processing. OBJECTIVE: The goal of the present study was to examine the relationship between chronic pain and cognition [executive functions (EF) and memory], while controlling for mood, in cognitively intact older persons and in patients with Alzheimer's disease (AD). METHODS: Two groups of subjects participated: 20 older persons without dementia and 19 patients in an early stage of probable AD who suffered from arthrosis/arthritis. Pain intensity and pain affect were assessed by the Colored Analogue Scale for Pain Intensity and for Pain Affect, the Faces Pain Scale (FPS) and the Number of Words Chosen-Affective (NWC-A). Level of depression and anxiety were evaluated by questionnaires. EF and memory were assessed by neuropsychological tests. RESULTS: The results show that significant correlations between specific cognitive functions, pain intensity and pain affect were lacking in the cognitively intact older persons. Cognition, in particular memory, appeared to be related to depressive symptoms. In contrast, a significant positive correlation was observed between EF, pain intensity and pain affect measured by the FPS in the AD group. CONCLUSIONS: Although older persons with depression were excluded, in studies on pain and cognition one should control for the presence of depressive symptoms in older persons with and without dementia.

Scherder EJ, Vuijk PJ, Swaab DF, van Someren EJ. · Department of Clinical Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands. · Exp Aging Res. · Pubmed #17364906 No free full text.

Abstract: The goal of the present study was to examine possible effects of right median nerve stimulation (RMNS) on memory in patients in a relatively early stage of probable Alzheimer's disease (AD). Seventeen AD patients were randomly assigned to an experimental group (n = 8) and a control group (n = 9) and treated with RMNS and sham RMNS, respectively, for 30 min a day, 5 days a week, for 6 weeks. Neuropsychological tests were used to assess memory processes. The results show that the various aspects of memory did not respond positively to RMNS. A study with a much longer treatment period is suggested before firm conclusions about the ineffectiveness of RMNS on memory in AD can be drawn.

Van Dijk KR, Luijpen MW, Van Someren EJ, Sergeant JA, Scheltens P, Scherder EJ. · Department of Neurocognition, Faculty of Psychology, Maastricht University, Maastricht, The Netherlands. · J Sleep Res. · Pubmed #17118098 No free full text.

Abstract: Rest-activity rhythm disruption is a prominent clinical feature of Alzheimer's disease (AD). The origin of the altered rest-activity rhythm is believed to be degeneration of the suprachiasmatic nucleus (SCN). In accordance with the 'use it or lose it' hypothesis of Swaab [Neurobiol Aging 1991, 12: 317-324] stimulation of the SCN may prevent age-related loss of neurons and might reactivate nerve cells that are inactive but not lost. Previous studies with relatively small sample sizes have demonstrated positive effects of peripheral electrical nerve stimulation on the rest-activity rhythm in AD patients. The present randomized, placebo-controlled, parallel-group study was meant to replicate prior findings of electrical stimulation in AD in a substantially larger group of AD patients. The experimental group (n = 31) received peripheral electrical nerve stimulation and the placebo group (n = 31) received sham stimulation. Effects of the intervention on the rest-activity rhythm were assessed by using wrist-worn actigraphs. Near-significant findings on the rest-activity rhythm partially support the hypothesis that neuronal stimulation enhances the rest-activity rhythm in AD patients. Interestingly, post-hoc analyses revealed significant treatment effects in a group of patients who were not using acetylcholinesterase inhibitors concomitantly. We conclude that more research is needed before firm general conclusions about the effectiveness of electrical stimulation as a symptomatic treatment in AD can be drawn. In addition, the present post-hoc findings indicate that future studies on non-pharmacological interventions should take medication use into account.

Oosterman JM, Scherder EJ. · Department of Clinical Neuropsychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. · J Clin Exp Neuropsychol. · Pubmed #16840242 No free full text.

Abstract: This study was intended to, meta-analytically, review whether the subtests of the Wechsler Adult Intelligence Scale are useful in differentiating between vascular dementia and Alzheimer's disease. We expected the Alzheimer's disease group to outperform the vascular dementia group on those subtests that require executive functions, whereas inferior performance of the Alzheimer's disease patients was expected on memory tests. Two steps in the analysis were undertaken in an attempt to clarify this issue. The first step consisted of including all studies examining Wechsler Adult Intelligence Scale subtest performance in vascular dementia and Alzheimer's disease patients. Secondly, a subcortical vascular dementia subgroup was distinguished and performance of this subgroup was compared to that of the Alzheimer's disease group.Overall, the analyses showed that both the vascular dementia and, more strongly, the subcortical vascular dementia group revealed decreased executive functions on several subtests compared to the Alzheimer's disease group. The Alzheimer's disease group showed inferior performance on a single semantic memory test only compared to both the vascular dementia and the subcortical vascular dementia groups. These results indicate that several subtests of the Wechsler Adult Intelligence Scale can differentiate between these two clinical groups, and that most of these tests reveal more impaired performance in the vascular dementia group.

Scherder EJ, van Tol MJ, Swaab DF. · Institute of Human Movement Sciences, University of Groningen, Groningen, The Netherlands. · Am J Phys Med Rehabil. · Pubmed #16788393 No free full text.

Abstract: In a previous study, low-frequency cranial electrostimulation did not improve cognition and (affective) behavior in patients with probable Alzheimer's disease. In the present study, 21 Alzheimer's disease patients, divided into an experimental (n = 11) and a control group (n = 10), were treated for 30 mins/day, 5 days/wk, for 6 wks with high-frequency cranial electrostimulation. Similar to the previous study, no improvements on cognition and (affective) behavior were found.

Cooper EB, Scherder EJ, Cooper JB. · Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA. · Neuropsychol Rehabil. · Pubmed #16350980 No free full text.

Abstract: The right median nerve can be stimulated electrically to help arouse the central nervous system for persons with reduced levels of consciousness. The mechanisms of central action include increased cerebral blood flow and raised levels of dopamine. There is 11 years of experience in the USA of using nerve stimulation for acute coma after traumatic brain injury. There is a much longer period of experience by neurosurgeons in Japan with implanted electrodes on the cervical spinal cord for persons in the persistent vegetative state (PVS). But the use of right median nerve electrical stimulation (RMNS) for patients in the subacute and chronic phases of coma is relatively new. Surface electrical stimulation to treat anoxic brain injury as well as traumatic brain injury is evolving. Novel applications of electrical stimulation in Amsterdam have produced cognitive behavioural effects in persons with early and mid-stage Alzheimer's disease employing transcutaneous electrical nerve stimulation (TENS). Improvements in short-term memory and speech fluency have also been noted. Regardless of the aetiology of the coma or reduced level of awareness, electrical stimulation may serve as a catalyst to enhance central nervous system functions. It remains for the standard treatments and modalities to retrain the injured brain emerging from reduced levels of consciousness.

Luijpen MW, Swaab DF, Sergeant JA, van Dijk KR, Scherder EJ. · Department of Clinical Neuropsychology, Vrije Universiteit, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. · Behav Brain Res. · Pubmed #15698902 No free full text.

Abstract: In previous studies, transcutaneous electrical nerve stimulation (TENS) was shown to have a positive effect on memory in Alzheimer's disease (AD) patients. Moreover, the reported effects appeared to be more beneficial in early stages of Alzheimer's disease compared to later stage intervention. Based on this stage-dependency, the present study examined the effects of TENS on memory in a preclinical stage of AD, i.e. in subjects with mild cognitive impairment (MCI). Our results suggest that TENS did not improve memory in a MCI population. Mechanisms that might underlie the absence of positive effects of the TENS treatment in a MCI population are discussed.

Scherder EJ, Bouma A. · Department of Clinical Psychology, Vrije Universiteit, The · Gerontology. · Pubmed #11111229 No free full text.

Abstract: BACKGROUND: In earlier studies, pain assessment in patients with Alzheimer's disease (AD) was conducted by interview, for which reliability is questionable considering the decline in expressive and receptive language abilities in AD. As similar language problems occur in young children, the reliability of pain assessment in this latter population is increased by employing visual analogue scales. OBJECTIVE: By employing visual analogue scales, the current study investigated whether (1) nondemented elderly persons and AD patients comprehend the purpose of the scales and (2) AD patients, compared to nondemented elderly persons, report suffering less pain intensity and pain affect. Methods: Three visual analogue scales, i.e. the Colored Analogue Scale (CAS), the Faces Pain Scale (FPS), and the Facial Affective Scale (FAS) were administered to patients in an early and midstage of AD and to nondemented elderly persons. RESULTS: The results show that the percentage of subjects who comprehended the CAS, FAS and FPS was for the nondemented elderly persons 100, 75 and 100%, respectively, for the early AD group 100, 50 and 60%, respectively, and for the midstage AD group 80, 20 and 30%, respectively. Furthermore, elderly persons without dementia reported experiencing more intense pain and pain affect than the early and midstage AD group. Interestingly, the early and midstage AD patients did not differ in reporting pain affect. CONCLUSION: Visual analogue scales may improve pain assessment in those AD patients who fully comprehend the meaning of the scales. As only the minority of midstage AD patients understood the purpose of the FAS and FPS, the search for tools, particularly to assess pain affect in this population, must continue.

Scherder EJ, Bouma A. · Department of Clinical Psychology, Vrije Universiteit, Amsterdam, The Netherlands. · Dement Geriatr Cogn Disord. · Pubmed #10629356 No free full text.

Abstract: The low use of analgesics in patients with Alzheimer's disease (AD), compared to nondemented elderly persons, is generally explained by (1) a lower prevalence of painful conditions in the former group and (2) undertreatment of pain due to a decrease in communicative abilities in AD. However, considering the neuropathology in limbic areas in this disorder, a decline in pain affect may also explain this phenomenon. In the present study, a newly developed questionnaire was applied to 20 elderly persons without dementia, 20 patients in an early stage and 20 patients in a midstage of AD. The questionnaire includes 10 pairs of painful situations, each pair consisting of an acute and a chronic affective painful situation. It was hypothesized that, compared to controls, AD patients during the course of the disease would report to suffer increasingly more from an acute than from a chronic, affective painful situation. The results support our hypothesis. Limitations of the present study are discussed.