31 Aug 2022

Part 2 of 2

Alzheimer’s and related dementias are diseases of aging, yet the oldest among us tend to be excluded from most studies aiming to find treatments for them. Either directly, via exclusion criteria in drug trials, or indirectly, because they are homebound, frail, or lack family members to drive them to appointments, people older than 80 are both the most cut off from interventions to delay dementia, and arguably in greatest need of them. The I-CONECT project, led by Hiroko Dodge of Oregon Health and Science University in Portland, arose in response.

This internet-based conversational engagement trial gave people older than 75 easy-to-use tablets, through which they held regular video chats for a year. A control group received a brief weekly phone call to check in. At the Alzheimer’s Association International Conference, held July 31 to August 4 in San Diego, Dodge and other OHSU scientists reported that cognitive scores improved in people with mild cognitive impairment who chatted regularly via video, while feelings of social connectedness grew among all participants, even those who received only a weekly call.

The findings support the idea that social contact can stave off cognitive decline, said Dodge. She believes social engagement delays cognitive decline not by thwarting neuropathology, but by bolstering cognitive reserve. Functional MRI scans from a small subset of I-CONECT participants hint that a boost in synaptic connectivity may underlie this.

Other findings presented at AAIC supported the benefit of exercise, and of multimodal lifestyle interventions, in warding off cognitive deterioration (see Part 1 of this story). Even among these more intense interventions, it seemed that social engagement played a part. Might a simple conversation via video chat four times per week provide some benefit on its own? In a session dedicated to I-CONECT at AAIC, researchers presented findings on primary, secondary, and exploratory endpoints of this Phase 2 trial.

I-CONECT targeted socially isolated people with normal cognition, or with MCI, older than 75. The experimental group took 30-minute video calls for 12 months. Participants chatted with trained interviewers who used images and prompts to stimulate a free-flowing conversation. They occurred four times per week for the first six months, and twice weekly after that. This group also received once-weekly 10-minute phone calls to monitor their social activities, health, and mood. The control group only received these weekly check-in calls. A quick screen of cognition, as per the Montreal Cognitive Assessment (MoCA), served as the primary outcome. Secondary outcomes included measures of executive function, emotional well-being, and episodic memory, while changes in speech, medication adherence, brain connectivity, and cerebral blood flow were among exploratory outcomes.

Prescribed Chatting. I-CONECT participants talked with conversation staff several times per week for a year. The staff used images and prompts to break the ice, then let conversations flow naturally. [Courtesy of Hiroko Dodge, OHSU.]

Out of more than 1,100 telephone screenings, the researchers managed to recruit 186 people—86 who were cognitively normal and 100 with MCI—into the trial. Dodge said that the trial aimed to recruit African Americans, and that this group was particularly reticent to join. Ultimately, the trial enrolled 20 percent black participants, a higher proportion than most prior clinical trials.

What did the scientists find? First, the COVID pandemic interfered with the trial. Though its intervention was via video chat, the cognitive assessments were being conducted in person before the pandemic started, and over the phone after that. However, the telephone version of the MoCA—called “blind MoCA”—eliminates all items that require visual engagement, therefore its scores are not directly comparable to the in-person test, Dodge explained. Following recommendations from their data safety monitory board, the researchers limited assessment of the primary outcome to findings from 56 people who had finished their six-month assessment before the pandemic.

Among this much smaller group, which included 25 people with normal cognition and 31 with MCI, the researchers found a benefit of video chats among participants with MCI. While MoCA scores declined in the control group over six months, scores in the video chat group improved, resulting in a 1.75-point higher six-month score relative to controls. This difference is equivalent to the effect of 10 years of aging, Dodge said. At 0.73, the Cohen’s d value—a measure of effect size—was quite high. A boost in the memory domain drove this MoCA result, Dodge reported. Participants with normal cognition did not benefit.

Due to the MoCA mismatch, Dodge did not present 12-month MoCA scores. She did report outcomes on secondary measures of category fluency, immediate recall, and delayed recall among the 186 people who completed the trial. Among the 100 with MCI, Dodge reported a 2-point bump in immediate recall scores at 12 months in people who received the video chats relative to weekly calls. Among cognitively normal participants, Dodge reported a 2.56-point benefit of the video chat intervention at six months (but not at 12 months) in category fluency, a measure of executive function. Not all cognitive measures improved at both time points, nor were they corrected for multiple comparisons. Still, Dodge believes the findings suggest a benefit of social contact for older people, particularly those with MCI. OHSU’s Meysam Asgari reported a boost in the complexity of speech used by participants in the video chat group.

OHSU's Kexin Yu presented findings on psychosocial well-being, a secondary outcome measured using the NIH Toolbox Emotional Battery. Yu reported that neither video chatting nor phone calls influenced the participants’ negative affect, which includes feelings of anger, sadness, stress, and fear. However, measures of social satisfaction improved in both over the course of the 12-month trial. Yu interpreted the findings as indicating that even a weekly 10-minute phone call can boost feelings of connectedness.

Patrick Pruitt of OHSU presented functional connectivity findings collected from a small subset of I-CONECT participants. He hypothesized that social engagement influences network connectivity in the brain. If true, this could be picked up via fMRI. After excluding low-quality scans caused by participants wiggling in the scanner, the analysis netted 50 fMRI scans at baseline but just 15—six in the weekly call group and nine in the video chat group—at both baseline and six months. Pruitt detected an uptick in connectivity within the dorsal attention network (DAN) in the video chat group relative to the weekly phone call group. Connectivity in other networks, including the default mode, executive control, and salience networks, did not differ between groups. Furthermore, Pruitt reported that at baseline, the level of connectivity within the DAN, but not any other network, correlated with scores on participants' delayed and immediate story recall.

In discussion, David Morgan of Michigan State University in Grand Rapids said he was impressed that MoCA scores rose with social engagement. “As someone who’s been working to reduce the neuropathology of AD, my expectation is more of a stabilization of the disease symptoms, rather than an improvement,” Morgan said. That participants improved suggests that non-pathological effects, such as a boost in network connectivity, might underlie the benefit, he added. 

Barry Greenberg of Johns Hopkins University in Baltimore, agreed. He added that behavioral and lifestyle interventions should be considered in conversations about combination therapy, which typically focus on different drugs. “A combination therapy could include cardiovascular health, an anti-pathology medication, together with these types of social interactions,” he said.

Morgan raised the idea of one day using robots to provide the social stimulus instead of live human beings, but Greenberg was skeptical. “We’re a social species,” he said. “The benefit of this intervention comes from the human interaction, with the full range of emotional expressions,” he said. For her part, Dodge agreed that artificial intelligence has come a long way in mimicking human interactions. It remains to be seen if the technology would be “human-like enough” to benefit socially isolated older people.

Whether delivered by a person or artificial intelligence, social interactions could prove to be a cost-effective way to delay the onset of dementia in populations most at risk for imminent decline, Dodge said. “Even delaying the onset of symptoms by a year would have an enormous impact,” she said. —Jessica Shugart

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References

News Citations

1. Lifestyle Interventions May Fend Off Decline; Social Contact Helps 31 Aug 2022

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