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Background: Detecting early signs of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) during the pre-symptomatic phase is becoming increasingly important for cost-effective clinical trials and also for deriving maximum benefit from currently available treatment strategies. However, distinguishing early signs of MCI from normal cognitive aging is difficult. Biomarkers have been extensively examined as early indicators of the pathological process for AD, but assessing these biomarkers is expensive and challenging to apply widely among pre-symptomatic community dwelling older adults. Here we propose assessment of social markers, which could provide an alternative or complementary and ecologically valid strategy for identifying the pre-symptomatic phase leading to MCI and AD. Methods: The data came from a larger randomized controlled clinical trial (RCT), where we examined whether daily conversational interactions using remote video telecommunications software could improve cognitive functions of older adult participants. We assessed the proportion of words generated by participants out of total words produced by both participants and staff interviewers using transcribed conversations during the intervention trial as an indicator of how two people (participants and interviewers) interact with each other in one-on-one conversations. We examined whether the proportion differed between those with intact cognition and MCI, using first, generalized estimating equations with the proportion as outcome, and second, logistic regression models with cognitive status as outcome in order to estimate the area under ROC curve (ROC AUC). Results: Compared to those with normal cognitive function, MCI participants generated a greater proportion of words out of the total number of words during the timed conversation sessions (p=0.01). This difference remained after controlling for participant age, gender, interviewer and time of assessment (p=0.03). The logistic regression models showed the ROC AUC of identifying MCI (vs. normals) was 0.71 (95% Confidence Interval: 0.54 – 0.89) when average proportion of word counts spoken by subjects was included univariately into the model. Conclusion: An ecologically valid social marker such as the proportion of spoken words produced during spontaneous conversations may be sensitive to transitions from normal cognition to MCI.

Background Trials aimed at preventing cognitive decline through cognitive stimulation among those with normal cognition or mild cognitive impairment are of significant importance in delaying the onset of dementia and reducing dementia prevalence. One challenge in these prevention trials is sample recruitment bias. Those willing to volunteer for these trials could be socially active, in relatively good health, and have high educational levels and cognitive function. These participants’ characteristics could reduce the generalizability of study results and, more importantly, mask trial effects. We developed a randomized controlled trial to examine whether conversation-based cognitive stimulation delivered through personal computers, a webcam and the internet would have a positive effect on cognitive function among older adults with normal cognition or mild cognitive impairment. To examine the selectivity of samples, we conducted a mass mail-in survey distribution among community-dwelling older adults, assessing factors associated with a willingness to participate in the trial. Methods Two thousand mail-in surveys were distributed to retirement communities in order to collect data on demographics, the nature and frequency of social activities, personal computer use and additional health-related variables, and interest in the prevention study. We also asked for their contact information if they were interested in being contacted as potential participants in the trial. Results Of 1,102 surveys returned (55.1% response rate), 983 surveys had complete data for all the variables of interest. Among them, 309 showed interest in the study and provided their contact information (operationally defined as the committed with interest group), 74 provided contact information without interest in the study (committed without interest group), 66 showed interest, but provided no contact information (interest only group), and 534 showed no interest and provided no contact information (no interest group). Compared with the no interest group, the committed with interest group were more likely to be personal computer users (odds ratio (OR) = 2.78), physically active (OR = 1.03) and had higher levels of loneliness (OR = 1.16). Conclusion Increasing potential participants’ familiarity with a personal computer and the internet before trial recruitment could increase participation rates and improve the generalizability of future studies of this type. Trial registration The trial was registered on 29 March 2012 at ClinicalTirals.gov (ID number NCT01571427).

Introduction Increasing social interaction could be a promising intervention for improving cognitive function. We examined the feasibility of a randomized controlled trial to assess whether conversation-based cognitive stimulation through personal computers, webcams, and a user-friendly interactive Internet interface had high adherence and a positive effect on cognitive function among older adults without dementia. Methods Daily 30-minute face-to-face communications were conducted during a 6-week trial period in the intervention group. The control group received only a weekly telephone interview. The cognitive status of normal subjects and those with mild cognitive impairment was operationally defined as a global clinical dementia rating of 0 and 0.5, respectively. Age, sex, education, mini mental state examination score, and clinical dementia rating score were balancing factors in randomization. The subjects were recruited using mass-mailing invitations. The pre- to postintervention differences in the cognitive test scores and loneliness scores were compared between the control and intervention groups using linear regression models. Results Eighty-three subjects participated (41 in the intervention group and 42 in the control group). Their mean ± standard deviation age was 80.5 ± 6.8 years. Adherence to the protocol was high. There was no dropout and mean percentage of days completed of the targeted trial days among the intervention group was 89% (range 77%–100%). Among the cognitively intact participants, the intervention group improved more than did the control group on a semantic fluency test ( P = .003) at the post-trial assessment and a phonemic fluency test ( P = .004) at the 18-week assessments. Among those with mild cognitive impairment, a trend ( P = .04) toward improved psychomotor speed was observed in the intervention group. Conclusion Daily conversations by way of user-friendly Internet communication programs demonstrated high adherence. Among the cognitively intact, the intervention group showed greater improvement in tests of language-based executive functions. Increasing daily social contacts through communication technologies could offer cost-effective home-based prevention methods. Additional studies with a longer follow-up duration are required to examine whether the intervention slows cognitive declines and delays the onset of dementia.