Declarative Learning, Priming, and Procedural Learning Performances comparing Individuals with Amnestic Mild Cognitive Impairment, and Cognitively Unimpaired Older Adults.

OBJECTIVE: While declarative learning is dependent on the hippocampus, procedural learning and repetition priming can operate independently from the hippocampus, making them potential targets for behavioral interventions that utilize non-declarative memory systems to compensate for the declarative learning deficits associated with hippocampal insult. Few studies have assessed procedural learning and repetition priming in individuals with amnestic mild cognitive impairment (aMCI). METHOD: This study offers an overview across declarative, conceptual repetition priming, and procedural learning tasks by providing between-group effect sizes and Bayes Factors (BFs) comparing individuals with aMCI and controls. Seventy-six individuals with aMCI and 83 cognitively unimpaired controls were assessed. We hypothesized to see the largest differences between individuals with aMCI and controls on declarative learning, followed by conceptual repetition priming, with the smallest differences on procedural learning. RESULTS: Consistent with our hypotheses, we found large differences between groups with supporting BFs on declarative learning. For conceptual repetition priming, we found a small-to-moderate between-group effect size and a non-conclusive BF somewhat in favor of a difference between groups. We found more variable but overall trivial differences on procedural learning tasks, with inconclusive BFs, in line with expectations. CONCLUSIONS: The current results suggest that conceptual repetition priming does not remain intact in individuals with aMCI while procedural learning may remain intact. While additional studies are needed, our results contribute to the evidence-base that suggests that procedural learning may remain spared in aMCI and helps inform behavioral interventions that aim to utilize procedural learning in this population.

Procedural learning, declarative learning, and working memory as predictors of learning the use of a memory compensation tool in persons with amnestic mild cognitive impairment.

Persons with amnestic Mild Cognitive Impairment (aMCI) are at risk for experiencing changes in their daily functioning due to their memory impairment. The Memory Support System (MSS), a compensatory calendaring system, was developed to support functional independence in persons with aMCI (pwaMCI). This cross-sectional study examined procedural learning, declarative learning, and working memory as predictors of MSS learning efficiency in pwaMCI. Sixty pwaMCI participated in MSS training. The Serial Reaction Time Test and Mirror Tracing Test were used to assess procedural learning. The Rey Auditory Verbal Learning Test and CogState One Card Learning were used to assess declarative learning and the CogState One Back task was used to assess working memory. Multiple regression analyses were conducted to assess if procedural learning, declarative learning, and working memory predicted MSS learning efficiency. This study showed that declarative learning predicted MSS learning efficiency in pwaMCI, with less consistent results for procedural learning and non-significant results for working memory. Findings suggest that success in teaching compensatory tools is greater when training is offered in early aMCI before declarative learning skill is fully lost. Future studies should assess additional strategies to facilitate MSS learning in advanced aMCI.

The impact of patient and partner personality traits on learning success for a cognitive rehabilitation intervention for patients with MCI.

The Memory Support System (MSS) is the memory compensation tool used in the HABIT Healthy Action to Benefit Independence and Thinking® Program. People diagnosed with mild cognitive impairment (pwMCI; n = 153) participated in this cognitive rehabilitative programme with a partner. We first aimed to determine if prior research on the positive impact of higher baseline cognitive status on successful MSS learning would be replicated in a new sample. We further evaluated the impact of the pwMCI's and partner's personality traits, as measured by the Ten Item Personality Inventory, on successful learning. Better global cognitive status was again shown to increase the odds for MSS learning success. In terms of personality, the highest odds of learning success occurred when the pwMCI was high in Openness to Experience (OR = 5.43), followed by high partner Openness (OR = 2.53) or high Openness in both the pwMCI and partner (OR = 2.31). In sum, when the pwMCI possessed both better cognitive status and openness to new experience they were better able to master a cognitive rehabilitation tool for MCI.

Computerized Cognitive Training (CCT) versus Yoga Impact on 12 Month Post Intervention Cognitive Outcome in Individuals with Mild Cognitive Impairment.

There is currently limited and mixed evidence for the cognitive benefits of Computerized Cognitive Training (CCT) and yoga in persons with Mild Cognitive Impairment (pwMCI). The objective of this study was to investigate the benefit of computerized cognitive training (CCT) vs. physical (yoga) intervention on cognitive abilities. Participants in this study were part of the larger Mayo Clinic's Healthy Action to Benefit Independence and Thinking (HABIT) program comparative effectiveness trial. The HABIT program is designed for pwMCI and their care partner and consists of five behavioral interventions: CCT, Memory Support System-Calendar (MSS-Calendar), wellness education, support groups, and yoga. The subtractive study design randomly withheld one of the interventions for a total of five study arms. Longitudinal mixed-effects regression models were used to investigate the hypothesis that CCT and yoga has a greater positive impact on psychomotor and basic attention abilities at 12 months post-intervention as compared to the other HABIT interventions. Findings showed CCT had a positive impact compared to yoga on the Cogstate psychomotor/attention composite at 12 months post-intervention (ES = 0.54; unadjusted p value = 0.007, adjusted p value = 0.021). The impact of yoga or combining CCT with yoga did not show statistically significant improvement. Continued CCT practice at home showed further benefit on psychomotor/attention at 12 months post-intervention. There was no significant benefit of CCT or yoga on Cogstate learning/working memory composite.

Innovation Inspired by COVID: A Virtual Treatment Program for Patients With Mild Cognitive Impairment at Mayo Clinic.

Limited access to mental health and behavioral interventions is a public health issue that predated and is further worsened by coronavirus disease 2019 (COVID-19) social distancing restrictions. The Healthy Action to Benefit Independence and Thinking (HABIT) program is a cognitive rehabilitation and wellness program for patients with a diagnosis of mild cognitive impairment and their partners that involves groups of up to 32 people (16 dyads) at a time. Thus, the public health recommendation to avoid groups at the start of the COVID-19 pandemic immediately impacted our ability to offer this treatment protocol. This brief report provides patient and partner satisfaction data as well as clinical outcomes with a virtual adaptation of the HABIT program developed because of the COVID-19 pandemic. At the time of their participation, patients who attended in-person sessions had an average age of 74.4 years and those who attended virtual sessions had an average age of 75.4 years (P=.60). Both groups had an average of 16.3 years of education (P=.95). Approximately half of the patients in both groups were male (30 of 57 [53%]), most were White (54 of 57 [95%]) and were accompanied to the program by a spouse (50 of 57 [88%]). Overall, patient and partner satisfaction with the HABIT program remained high, ranging from a mean score of 5.8 to 6.6 on a rating scale of 1 to 7 for patients and partners, and clinical outcomes remained consistent with our face-to-face formatting when compared with pre-COVID pandemic sessions. The most notable changes across both formats were improvements in patient anxiety (Cohen's d=0.25 face-to-face; d=0.39 virtual), partner anxiety (d=0.37 face-to-face; d=0.34 virtual), and partner depression (d=0.37 face-to-face; d=0.35 virtual). This preliminary program evaluation suggests that transitioning the HABIT program to virtual formatting provides high-quality care similar to our in-person care models. Ongoing program evaluation is planned as we continue using virtual treatment for safety. Even after COVID-19 pandemic public health restrictions are lifted, these findings will have continued relevance to ongoing demand for telehealth.

Comparative Effects of Physical Exercise and Other Behavioral Interventions on Functional Status Outcomes in Mild Cognitive Impairment.

OBJECTIVES: Lifestyle modifications for those with mild cognitive impairment (MCI) may promote functional stability, lesson disease severity, and improve well-being outcomes such as quality of life. The current analysis of our larger comparative effectiveness study evaluated which specific combinations of lifestyle modifications offered as part of the Mayo Clinic Healthy Action to Benefit Independence in Thinking (HABIT) program contributed to the least functional decline in people with MCI (pwMCI) over 18 months. METHODS: We undertook to compare evidence-based interventions with one another rather than to a no-treatment control group. The interventions were five behavioral treatments: computerized cognitive training (CCT), yoga, Memory Support System (MSS) training, peer support group (SG), and wellness education (WE), each delivered to both pwMCI and care partners, in a group-based program. To compare interventions, we randomly withheld one of the five HABIT® interventions in each of the group sessions. We conducted 24 group sessions with between 8 and 20 pwMCI-partner dyads in a session. RESULTS: Withholding yoga led to the greatest declines in functional ability as measured by the Functional Activities Questionnaire and Clinical Dementia Rating. In addition, memory compensation (calendar) training and cognitive exercise appeared to have associations (moderate effect sizes) with better functional outcomes. Withholding SG or WE appeared to have little effect on functioning at 18 months. CONCLUSIONS: Overall, these results add to the growing literature that physical exercise can play a significant and lasting role in modifying outcomes in a host of medical conditions, including neurodegenerative diseases.

Comparative Effectiveness of Behavioral Interventions on Quality of Life for Older Adults With Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Recommendations to engage in behavioral strategies to combat clinically significant cognitive and behavioral symptoms are routinely given to persons with mild cognitive impairment (MCI). The comparative effectiveness of these behavioral interventions is not well understood. Objective: To compare the incremental effects of combinations of 5 behavioral interventions on outcomes of highest importance to patients with MCI. Design, Setting, and Participants: In this multisite, cluster randomized, multicomponent comparative effectiveness trial, 272 patients from 4 academic medical outpatient centers (Mayo Clinic, Rochester, Minnesota; Mayo Clinic, Scottsdale, Arizona; Mayo Clinic, Jacksonville, Florida; and University of Washington, Seattle) were recruited from September 1, 2014, to August 31, 2016, with last follow-up March 31, 2019. All participants met the National Institute on Aging-Alzheimer's Association criteria for MCI. Interventions: The intervention program was modeled on the Mayo Clinic Healthy Action to Benefit Independence and Thinking (HABIT) program, a 50-hour group intervention conducted during 2 weeks, including memory compensation training, computerized cognitive training, yoga, patient and partner support groups, and wellness education. In our study, 1 of 5 interventions was randomly selected to be withheld for each intervention group. Participants and their partners had 1-day booster sessions at 6 and 12 months after intervention. Main Outcomes and Measures: Quality-of-life measurement of participants with MCI at 12 months was the primary outcome, selected based on the preference rankings of previous program participants. Mood, self-efficacy, and memory-based activities of daily living were also highly ranked. Results: A total of 272 participants (mean [SD] age, 75 [8] years; 160 [58.8%] male and 112 [41.2%] female) were enrolled in this study, with 56 randomized to the no yoga group, 54 to no computerized cognitive training, 52 to no wellness, 53 to no support, and 57 to no memory support system. The greatest effect size for quality of life was between the no computerized cognitive training and no wellness education groups at 0.34 (95% CI, 0.05-0.64). In secondary analyses, wellness education had a greater effect on mood than computerized cognitive training (effect size, 0.53; 95% CI, 0.21-0.86), and yoga had a greater effect on memory-related activities of daily living than support groups (effect size, 0.43; 95% CI, 0.13-0.72). Conclusions and Relevance: These results provide further support for behavioral interventions for persons with MCI. Different outcomes were optimized by different combinations of interventions. These findings provide an initial exploration of the effect of behavioral interventions on patient-advocated outcomes in persons with MCI. Trial Registration: ClinicalTrials.gov identifier: NCT02265757.

Computer versus Compensatory Calendar Training in Individuals with Mild Cognitive Impairment: Functional Impact in a Pilot Study.

This pilot study examined the functional impact of computerized versus compensatory calendar training in cognitive rehabilitation participants with mild cognitive impairment (MCI). Fifty-seven participants with amnestic MCI completed randomly assigned calendar or computer training. A standard care control group was used for comparison. Measures of adherence, memory-based activities of daily living (mADLs), and self-efficacy were completed. The calendar training group demonstrated significant improvement in mADLs compared to controls, while the computer training group did not. Calendar training may be more effective in improving mADLs than computerized intervention. However, this study highlights how behavioral trials with fewer than 30-50 participants per arm are likely underpowered, resulting in seemingly null findings.

Three-word recall in normal aging.

Three-word recall tasks are widely used as brief measures of verbal memory function, although interpretation of performance is complicated by variations in test instructions and procedures. The purpose of this study was to examine 3-word recall performance in samples of healthy subjects aged 5275 (M age = 70) and age 7692 (M age = 82) compared to patients with Alzheimer's Disease (AD) when explicit prompts to remember the words were given. Those in the younger aging group remembered significantly more words than those in the older sample after a brief delay (M= 2.8 and 2.3, respectively). However, the majority of control subjects recalled 2 or 3 words after the delay, with only 3% of the 5075 year old group and 17% of the 76+ year old group recalling 0 or 1 word on delayed recall. This is in stark contrast to the 87% of individuals with AD who recalled 0 or 1 word. Even though 3-word recall performance decreases with age, good recall (2 or 3 words) can be expected in most cases of normal aging.

Association between Dementia Rating Scale performance and neurocognitive domains in Alzheimer's disease.

The Dementia Rating Scale (DRS; Mattis, 1976, 1988) is commonly used in the assessment of dementia, although little is known about the relationship of performance on this test to specific cognitive deficits in Alzheimer's disease (AD). Additionally, cognitive profiles have not been investigated across different levels of dementia as determined by the DRS. A sample of 133 individuals diagnosed with possible or probable AD was administered the DRS as part of a comprehensive neuropsychological evaluation. Composite scores for the cognitive domains of attention, executive functioning, visuospatial skills, language abilities, immediate recall, and delayed memory were derived by averaging demographically corrected T scores of key measures. Individual domain scores were also averaged to develop a global index score. Pearson correlations between composite and total DRS scores were highly significant (p<.001) for all domains and the global index score, with the exception of delayed memory, which showed a floor effect. When the sample was divided into mild and moderate-to-severe groups to examine the effects of disease severity on the relationship between the DRS and standard neurocognitive domain scores, the resulting mean neuropsychological profile scores were significantly different while maintaining a parallel pattern of impairment across domains. Results demonstrate the relationship between the DRS and standard cognitive domain functions, which appears to underscore the validity and robustness of the DRS in characterizing patterns of cognitive impairment across the AD spectrum.