Hippocampal connectivity and memory decline in cognitively intact APOE ε4 carriers.

INTRODUCTION: Resting-state functional magnetic resonance imaging (fMRI) graph theory may help detect subtle functional connectivity changes affecting memory prior to impairment. METHODS: Cognitively normal apolipoprotein E (APOE) ε4 carriers/noncarriers underwent longitudinal cognitive assessment and one-time MRI. The relationship of left/right hippocampal connectivity and memory trajectory were compared between carriers/noncarriers. RESULTS: Steepness of verbal memory decline correlated with decreased connectivity in the left hippocampus, only among APOE ε4 carriers. Right hippocampal metrics were not correlated with memory and there were no significant correlations in the noncarriers. Verbal memory decline correlated with left hippocampal volume loss for both carriers and noncarriers, with no other significant volumetric findings. DISCUSSION: Findings support early hippocampal dysfunction in intact carriers, the AD disconnection hypothesis, and left hippocampal dysfunction earlier than the right. Combining lateralized graph theoretical metrics with a sensitive measure of memory trajectory allowed for detection of early-stage changes in APOE ε4 carriers before symptoms of mild cognitive impairment are present. HIGHLIGHTS: Graph theory connectivity detects preclinical hippocampal changes in APOE ε4 carriers. The AD disconnection hypothesis was supported in unimpaired APOE ε4 carriers. Hippocampal dysfunction starts asymmetrically on the left.

Cognition Before and After COVID-19 Disease in Older Adults: An Exploratory Study.

BACKGROUND: Older age is a major risk factor for severe COVID-19 disease which has been associated with a variety of neurologic complications, both acutely and chronically. OBJECTIVE: We sought to determine whether milder COVID-19 disease in older vulnerable individuals is also associated with cognitive and behavioral sequelae. METHODS: Neuropsychological, behavioral, and clinical outcomes before and after contracting COVID-19 disease, were compared in members of two ongoing longitudinal studies, the Arizona APOE Cohort and the national Alzheimer's Disease Research Center (ADRC). RESULTS: 152 APOE and 852 ADRC cohort members, mean age overall roughly 70 years, responded to a survey that indicated 21 APOE and 57 ADRC members had contracted COVID-19 before their ensuing (post-COVID) study visit. The mean interval between test sessions that preceded and followed COVID was 2.2 years and 1.2 years respectively for the APOE and ADRC cohorts. The magnitude of change between the pre and post COVID test sessions did not differ on any neuropsychological measure in either cohort. There was, however, a greater increase in informant (but not self) reported cognitive change in the APOE cohort (p = 0.018), but this became nonsignificant after correcting for multiple comparisons. CONCLUSION: Overall members of both cohorts recovered well despite their greater age-related vulnerability to more severe disease.

Behavioral Interventions in Mild Cognitive Impairment (MCI): Lessons from a Multicomponent Program.

Comparative effectiveness of behavioral interventions to mitigate the impacts of degeneration-based cognitive decline is not well understood. To better address this gap, we summarize the studies from the Healthy Action to Benefit Independence & Thinking (HABIT®) program, developed for persons with mild cognitive impairment (pwMCI) and their partners. HABIT® includes memory compensation training, computerized cognitive training (CCT), yoga, patient and partner support groups, and wellness education. Studies cited include (i) a survey of clinical program completers to establish outcome priorities; (ii) a five-arm, multi-site cluster randomized, comparative effectiveness trial; (iii) and a three-arm ancillary study. PwMCI quality of life (QoL) was considered a high-priority outcome. Across datasets, findings suggest that quality of life was most affected in groups where wellness education was included and CCT withheld. Wellness education also had greater impact on mood than CCT. Yoga had a greater impact on memory-dependent functional status than support groups. Yoga was associated with better functional status and improved caregiver burden relative to wellness education. CCT had the greatest impact on cognition compared to yoga. Taken together, comparisons of groups of program components suggest that knowledge-based interventions like wellness education benefit patient well-being (e.g., QoL and mood). Skill-based interventions like yoga and memory compensation training aid the maintenance of functional status. Notably, better adherence produced better outcomes. Future personalized intervention approaches for pwMCI may include different combinations of behavioral strategies selected to optimize outcomes prioritized by patient values and preferences.

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.

Compensatory and Lifestyle-Based Brain Health Program for Subjective Cognitive Decline: Self-Implementation versus Coaching.

Although recent studies have explored the potential of multidomain brain health programs, there is a dearth of literature on operationalizing this research to create a clinical treatment program specifically for subjective cognitive decline (SCD). Patients seen by geriatricians in primary care and by behavioral neurology services at our institution presenting with SCD were recruited via a patient-appropriate flyer. After all participants had a 1-h brain health consultation with a neuropsychologist and were provided with program materials, they were randomized to attend a 10-week intervention designed to support program implementation (N = 10) or the control group of implementing the program on their own (N = 11). The program included (1) a calendar-based executive and memory support system for compensatory training and (2) training in healthy lifestyle. There were no significant differences between groups for any outcomes. Participants across both groups showed significant improvements with moderate effect sizes in compensatory strategy use, anxiety symptoms, and daily functioning, which were sustained through 6-month follow-up. They also increased physical activity by the end of the intervention period but did not sustain this through 6-month follow-up. Our pilot study demonstrates preliminary feasibility of a cognitive compensatory and lifestyle-based brain health program. Additional research is recommended to further develop two potentially scalable implementation strategies-coaching and self-implementation after brief consultation.

Latent Factor Structure of Outcome Measures Used in the HABIT® Mild Cognitive Impairment Intervention Programs.

BACKGROUND: In Alzheimer's disease and related disorders (ADRD) research, common outcome measures include cognitive and functional impairment, as well as persons with mild cognitive impairment (pwMCI) and care partner self-reported mood and quality of life. Studies commonly analyze these measures separately, which potentially leads to issues of multiple comparisons and/or multicollinearity among measures while ignoring the latent constructs they may be measuring. OBJECTIVE: This study sought to examine the latent factor structure of a battery of 12-13 measures of domains mentioned above, used in a multicomponent behavioral intervention (The HABIT® program) for pwMCI and their partners. METHODS: Exploratory factor analysis (EFA) involved 214 pwMCI-partner pairs. Subsequent Confirmatory factor analyses (CFA) used 730 pairs in both pre- and post-intervention conditions. RESULTS: EFA generated a three-factor model. Factors could be characterized as partner adjustment (29.9%), pwMCI adjustment (18.1%), and pwMCI impairment (12.8%). The subsequent CFA confirmed our findings, and the goodness-of-fit for this model was adequate in both the pre- (CFI = 0.937; RMSEA = 0.057, p = 0.089) and post-intervention (CFI = 0.942; RMSEA = 0.051, p = 0.430) groups. CONCLUSION: Results demonstrated a stable factor structure across cohorts and intervention conditions suggesting that three broad factors may provide a straightforward and meaningful model to assess intervention outcome, at least during the MCI phase of ADRD.

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.

Improved Prediction of Imminent Progression to Clinically Significant Memory Decline Using Surface Multivariate Morphometry Statistics and Sparse Coding.

BACKGROUND: Besides their other roles, brain imaging and other biomarkers of Alzheimer's disease (AD) have the potential to inform a cognitively unimpaired (CU) person's likelihood of progression to mild cognitive impairment (MCI) and benefit subject selection when evaluating promising prevention therapies. We previously described that among baseline FDG-PET and MRI measures known to be preferentially affected in the preclinical and clinical stages of AD, hippocampal volume was the best predictor of incident MCI within 2 years (79%sensitivity/78%specificity), using standard automated MRI volumetric algorithmic programs, binary logistic regression, and leave-one-out procedures. OBJECTIVE: To improve the same prediction by using different hippocampal features and machine learning methods, cross-validated via two independent and prospective cohorts (Arizona and ADNI). METHODS: Patch-based sparse coding algorithms were applied to hippocampal surface features of baseline TI-MRIs from 78 CU adults who subsequently progressed to amnestic MCI in approximately 2 years ("progressors") and 80 matched adults who remained CU for at least 4 years ("nonprogressors"). Nonprogressors and progressors were matched for age, sex, education, and apolipoprotein E4 allele dose. We did not include amyloid or tau biomarkers in defining MCI. RESULTS: We achieved 92%prediction accuracy in the Arizona cohort, 92%prediction accuracy in the ADNI cohort, and 90%prediction accuracy when combining the two demographically distinct cohorts, as compared to 79%(Arizona) and 72%(ADNI) prediction accuracy using hippocampal volume. CONCLUSION: Surface multivariate morphometry and sparse coding, applied to individual MRIs, may accurately predict imminent progression to MCI even in the absence of other AD biomarkers.

Memory Support System training in mild cognitive impairment: Predictors of learning and adherence.

This study aimed to identify predictors of learning and adherence to a previously validated compensatory calendar and note-taking system (Memory Support System; MSS) in persons with amnestic mild cognitive impairment (aMCI). Age, education, global cognition, depression, and memory-related self-efficacy were studied as predictors of individuals' ability to learn the use of the MSS during the two-week training and of their adherence to the MSS 6, 12, and 18 months after training. How well an individual was able to learn the use of the MSS was itself examined as a predictor of adherence. Two-hundred-and-fifteen older adults with aMCI and their study partners (e.g., spouse, adult child) received MSS training one-hour daily for 10 days. Ordinal logistic regression analyses indicated that (1) global cognition predicted MSS learning at end of training, and (2) MSS learning at end of trainng predicted MSS adherence at 6, 12, and 18 months post-training. The current study suggests that offering compensatory strategies as early as possible for those with MCI might be of most benefit, and might have implications for long-term adherence.

Psychometric properties of the self-efficacy for managing mild cognitive impairment scale.

OBJECTIVES: We adapted a self-efficacy measure for managing chronic illness to be specific to persons with mild cognitive impairment (pwMCI). The aim of this study was to investigate the psychometric properties of the scale, the self-efficacy for managing MCI scale, for use in research. METHODS: Analyses involved data from pwMCI enrolled in a behavioral intervention study that completed the measure five times from intervention enrollment to 18-month post-intervention. Factor structure, construct validity, internal consistency, and test-retest reliability were analyzed. RESULTS: Factor analysis identified two factors, related to self-efficacy for daily activities and managing MCI, which corresponded with domains from the original chronic illness self-efficacy scale. Consistent with prior research, construct validity analysis suggested an association between memory-loss self-efficacy and psychosocial distress, but not cognitive or functional ability. Further analyses supported the scale's internal and test-retest reliability. CONCLUSIONS: Currently, no "gold standard" scale of memory-loss self-efficacy for pwMCI exists, despite the positive impact self-efficacy may have on modifiable health behaviors. Overall, results supported the notion that the scale is a valid and reliable measure of memory-loss self-efficacy for pwMCI.

Interaction Between BDNF Val66Met and APOE4 on Biomarkers of Alzheimer's Disease and Cognitive Decline.

BACKGROUND: Whether brain-derived neurotrophic factor (BDNF) Met carriage impacts the risk or progression of Alzheimer's disease (AD) is unknown. OBJECTIVE: To evaluate the interaction of BDNF Met and APOE4 carriage on cerebral metabolic rate for glucose (CMRgl), amyloid burden, hippocampus volume, and cognitive decline among cognitively unimpaired (CU) adults enrolled in the Arizona APOE cohort study. METHODS: 114 CU adults (mean age 56.85 years, 38% male) with longitudinal FDG PET, magnetic resonance imaging, and cognitive measures were BDNF and APOE genotyped. A subgroup of 58 individuals also had Pittsburgh B (PiB) PET imaging. We examined baseline CMRgl, PiB PET amyloid burden, CMRgl, and hippocampus volume change over time, and rate of change in cognition over an average of 15 years. RESULTS: Among APOE4 carriers, BDNF Met carriers had significantly increased amyloid deposition and accelerated CMRgl decline in regions typically affected by AD, but without accompanying acceleration of cognitive decline or hippocampal volume changes and with higher baseline frontal CMRgl and slower frontal decline relative to the Val/Val group. The BDNF effects were not found among APOE4 non-carriers. CONCLUSION: Our preliminary studies suggest that there is a weak interaction between BDNF Met and APOE4 on amyloid-ß plaque burden and longitudinal PET measurements of AD-related CMRgl decline in cognitively unimpaired late-middle-aged and older adults, but with no apparent effect upon rate of cognitive decline. We suggest that cognitive effects of BDNF variants may be mitigated by compensatory increases in frontal brain activity-findings that would need to be confirmed in larger studies.

Impact of Zumba on Cognition and Quality of Life is Independent of APOE4 Carrier Status in Cognitively Unimpaired Older Women: A 6-Month Randomized Controlled Pilot Study.

OBJECTIVE: To investigate the association of a 6-month Zumba intervention with cognition and quality of life among older cognitively unimpaired apolipoprotein ∊4 (APOE4) carrier and noncarrier women. METHODS: Fifty-three women were randomly assigned to either twice-weekly Zumba group classes or maintenance of habitual exercise (control group) for 6 months. At baseline, 3, and 6 months, all participants underwent neuropsychological, physical activity, and quality-of-life assessments. RESULTS: Overall, neuropsychological test scores and level of physical activity did not differ between intervention and control groups at any time. However, compared to the control group, quality of life was higher at 3 months, and visuospatial working memory and response inhibition improved more in the intervention group by 6 months. Apolipoprotein ∊4 status did not affect the results. DISCUSSION: Zumba may strengthen performance on visuospatial working memory among cognitively unimpaired older women but this needs to be tested in a larger clinical trial.

Functional ability is associated with higher adherence to behavioral interventions in mild cognitive impairment.

Objective: Behavioral interventions during early memory decline hold promise in delaying the development of dementia. In the present study, participants in a multimodal behavioral intervention study were assessed for post-intervention adherence and predictors of adherence.Methods: Participants (N = 272, mean age = 75.04 ± 7.54) diagnosed with amnestic Mild Cognitive Impairment (aMCI) were assigned to intervention groups receiving four out of five behavioral intervention components, including yoga, memory compensation training, computerized cognitive training, support groups, and/or wellness education. Length of the intervention was 10 days, 4 h per day, with post-intervention follow-up at 6, 12, and 18 months.Results: Two-hundred and thirty-seven participants completed the 6-month post-intervention follow-up measures, 228 participants completed the 12-month measures, and 218 participants completed the 18-month measures. Participants fully adhered to a mean of 2 out of the 4 taught intervention components. Eighty-nine percent of participants were at least partially adherent to one or more taught intervention components at 6-, 12-, and 18-month post-intervention follow-up. Physical activity was the most adhered to intervention while group support was the least adhered to intervention across all three follow-up time-points. Higher educational level, higher baseline depressive symptoms, higher baseline global cognitive functioning, and better baseline and concurrent functional abilities were associated post-intervention adherence.Conclusion: Changes in functional abilities are associated with disease progression among persons with aMCI. In the present study, individuals with aMCI who have higher education, higher depressive symptoms, and better baseline functioning abilities are more likely to adhere to behavioral intervention components over time. Post-intervention adherence also associates with concurrent daily function.

Neuropsychological decline up to 20 years before incident mild cognitive impairment.

INTRODUCTION: Some Alzheimer's disease biomarker studies found amyloid changes 20 years or more in advance of expected symptoms, while cognitive changes lagged for more than a decade, but this apparent lag might reflect the sensitivities of the biomarker and cognitive assays used. How far in advance of incident amnestic mild cognitive impairment (MCI) does cognition begin to decline? METHODS: Longitudinal neuropsychological study of an apolipoprotein E e4 enriched cohort of cognitively normal individuals at entry. Linear mixed models for MCI converters (n = 65) and nonconverters (n = 719) fitted for each neuropsychological measure; annual changes compared between groups before and after linear model intersections (inflection points). RESULTS: 34 of 35 cognitive measures and 9 of 18 behavioral measures declined faster post-inflection in the MCI converters; the earliest cognitive inflection point was nearly 20 years in advance of MCI diagnosis. DISCUSSION: The preclinical duration of cognitive and behavioral changes approaches the earliest reported biomarker changes.

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.

Self-Efficacy Mediates the Association Between Physical Function and Perceived Quality of Life in Individuals with Mild Cognitive Impairment.

BACKGROUND: Research has shown that individuals with mild cognitive impairment (MCI) value quality of life (QoL) above and beyond cognitive function or other potential outcomes in MCI. There is evidence supporting the negative impact of poor physical function on QoL ratings. OBJECTIVE: The study explored whether a modified measure of self-efficacy for managing MCI and education mediated and/or moderated the relationship between physical function and QoL in persons with MCI. METHODS: Baseline data from 200 participants with MCI were obtained from a larger study assessing the effectiveness of a behavioral intervention. Physical function was assessed by the Short Physical Performance Battery. QoL was assessed with the Quality of Life in Alzheimer's Disease scale. Memory-related self-efficacy was assessed using a modified 9-item version of the Chronic Disease Self-Efficacy Scales. Mediation and moderation analyses tested the hypotheses that self-efficacy and education alter the association between physical function and QoL in individuals with MCI. All analyses were adjusted for age, cognitive severity, and sex. RESULTS: Self-efficacy for managing MCI was a significant mediator of the association between physical function and perceived QoL. Individuals with better physical function reported higher self-efficacy which was associated with higher QoL ratings. CONCLUSIONS: Greater self-efficacy for managing MCI mediated the negative association between physical function and quality of life in this exploratory study. Interventions aimed at enhancing memory self-efficacy in MCI may improve perceived QoL, even in the presence of poor physical function. Future research is needed to investigate this further.

Neuropsychological comparison of incident MCI and prevalent MCI.

INTRODUCTION: Little empirical work has been done to examine differences between mild cognitive impairment (MCI) diagnosed in research settings with longitudinal data (incident MCI) and MCI diagnosed in clinical settings (prevalent MCI). Because Alzheimer's disease progresses over a clinicopathological continuum, we examined the cognitive differences between these two different sources of MCI patients. METHODS: We compared 52 consecutively identified patients with prevalent amnestic MCI with 53 incident amnestic MCI participants from the Arizona APOE study. Neuropsychological data from common tests were compared encompassing four cognitive domains and one global indicator. RESULTS: Prevalent MCI cases performed significantly worse than incident MCI cases on global as well as domain-specific measures. DISCUSSION: By the time patients seek evaluation for memory loss, they have more severe single domain, amnestic MCI than research subjects with incident MCI. Studies of MCI should distinguish incident and prevalent not just single- and multiple-domain MCI.