You will be provided with the titles and abstracts of a collection of medical RCT reports studying a clinical question -- for instance, the efficacy of an intervention on some medical outcome. Please write a few sentences synthesizing the findings of these reports, which could serve as a conclusion section for a systematic review article. Your response should not include any other text. The RCT reports are below.



Title 1:
Transcutaneous electrical nerve stimulation (TENS) improves the rest-activity rhythm in midstage Alzheimer's disease.
Abstract 1:
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.


Title 2:
Effects of transcutaneous electrical nerve stimulation on memory and behavior in Alzheimer's disease may be stage-dependent.
Abstract 2:
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.
                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.
                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.
                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.


Title 3:
Effects of "isolated" transcutaneous electrical nerve stimulation on memory and affective behavior in patients with probable Alzheimer's disease.
Abstract 3:
In previous studies, transcutaneous electrical nerve stimulation (TENS), tactile stimulation, and a combination of the two resulted in cognitive and affective improvements in patients with Alzheimer's disease (AD). As in those studies the therapist was present during the treatment of the experimental and control group (sham stimulation), a positive effect of the combination of TENS with interpersonal communication could not be excluded. Therefore, the effects of "isolated" TENS, i.e., in the absence of the therapist, on memory and affective disturbances in AD patients were examined.
                Eighteen subjects (78-92 years old) met the NINCDS-ADRDA criteria for the clinical diagnosis of probable AD. To evaluate treatment effects, the experimental group (9) and the control group (9) underwent a number of neuropsychological tests and two observation scales.
                Treatment effects were observed for nonverbal short-term (Visual Memory) and long-term (Face Recognition) memory, word fluency (Verbal Fluency), and need of help, whereas patients' affective behavior did not improve.
                The results of the present study show that isolated TENS has a positive effect on patients' cognitive and independent functioning; however, isolated TENS appeared not to have a therapeutic effect on patients' affective behavior.


Title 4:
Favorable effect of transcranial electrostimulation on behavior disorders in elderly patients with dementia: a double-blind study.
Abstract 4:
The efficacy of transcranial electrostimulation for sleep-wake and behavior disorders in elderly patients with dementia was tested in a double-blind study. The subjects were 27 inpatients with multi-infarct dementia (12 males and 15 females, aged 58-86). They were randomly divided into two groups: active treatment (n = 14) and placebo treatment (n = 13). For electrostimulation, a device (HESS-100) was used which delivered repetitive rectangular electric pulses of 6-8 V at increasing frequencies from 6 to 80 Hz, each pulse lasting 0.2 ms and with a root mean square value of 256-530 microA. Electrostimulation was performed for 20 minutes from 10:00 h every morning. The active or placebo treatment was performed for 2 weeks in each group. The electrostimulation was significantly effective in behavior disorders such as wandering or nocturnal delirium, and decreased motivation during the daytime. It was also effective in improving night sleep. Electroencephalograms confirmed increased vigilance levels in the daytime both during and after the treatment.


Title 5:
Cranial electrostimulation (CES) in patients with probable Alzheimer's disease.
Abstract 5:
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.


Title 6:
Effects of low-frequency cranial electrostimulation on the rest-activity rhythm and salivary cortisol in Alzheimer's disease.
Abstract 6:
In previous studies, cranial electrostimulation (CES) had positive effects on sleep in depressed patients and in patients with vascular dementia. The present study examined the effects of low-frequency CES on the rest-activity rhythm and cortisol levels of patients with probable Alzheimer's disease (AD).
                It was hypothesised that a decreased level of cortisol would parallel a positive effect of low-frequency CES on nocturnal restlessness. Sixteen AD patients were randomly assigned to an experimental group (n = 8) or a control group (n = 8). The experimental group was treated with CES, whereas the control group received sham stimulation, for 30 minutes a day, during 6 weeks. The rest-activity rhythm was assessed by actigraphy. Cortisol was measured repeatedly in the saliva throughout the day by means of salivette tubes.
                Low-frequency CES did not improve the rest-activity rhythm in AD patients. Moreover, both groups showed an increase instead of a decrease in the level of cortisol.
                These preliminary results suggest that low-frequency CES has no positive effect on the rest-activity rhythm in AD patients. An alternative research design with high-frequency CES in AD is discussed.


Title 7:
Effects of transcutaneous electrical nerve stimulation (TENS) on cognition and behaviour in aging.
Abstract 7:
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.


Title 8:
Transcutaneous electrical nerve stimulation (TENS) improves circadian rhythm disturbances in Alzheimer disease.
Abstract 8:
In patients with Alzheimer disease (AD), an irregular day-night rhythm with behavioral restlessness during the night makes a strong demand on caregivers and is among the most important reasons for institutionalization. A dysfunctioning circadian timing system is supposed to underlie the disturbance or at least to contribute to it. The disturbance improves with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. Because recent studies have indicated both direct and indirect spinal projections to the SCN, we investigated whether excitation of spinal neurons by means of transcutaneous electrical nerve stimulation (TENS) could also improve circadian rhythm disturbances in AD patients. The actigraphically obtained rest-activity rhythm of 14 AD patients showed an improvement in its coupling to Zeitgeber after TENS treatment but not after placebo treatment.
Although a number of studies suggest that TENS may produce short lived improvements in some neuropsychological or behavioural aspects of dementia, the limited presentation and availability of data from these studies does not allow definite conclusions on the possible benefits of this intervention. Since most of the currently published studies are well designed, although the numbers of subjects in each study is small, analysis of the complete original data from these and/or future studies may allow more definitive conclusions to be drawn.