Mild Cognitive Impairment Sample Research Articles

Informing etiological heterogeneity of mild cognitive impairment and risk for progression to dementia with plasma p-tau217.

Mild cognitive impairment (MCI) is a clinical diagnosis representing early symptom changes with preserved functional independence. There are multiple potential etiologies of MCI. While often presumed to be related to Alzheimer's disease (AD), other neurodegenerative and non-neurodegenerative causes are common. Wider availability of relatively non-invasive plasma AD biomarkers, such as p-tau217, can provide invaluable insights into MCI clinico-pathology and the associated implications for symptom etiology, prognosis (e.g., risk for progression to dementia), and treatment options. The main goal of this study was to evaluate differences between individuals with MCI with and without plasma p-tau217 biomarker evidence of AD (MCIAD+ and MCIAD-) as well as a control group of clinically normal older adults with negative AD biomarkers (CNAD-). We evaluated group differences in demographics, recruitment, clinical scales, fluid biomarkers, and brain imaging. We further probed these factors as independent contributors to symptoms among MCIAD- participants, for whom symptom etiology is most poorly understood. Lastly, in a subset of participants followed longitudinally, we investigated how these factors related to odds of clinical progression to dementia. We conducted an observational cross-sectional and longitudinal clinical research study. Study groups were compared cross-sectionally on demographics, recruitment, clinical measures, and biomarkers (chi square analyses, analyses of covariance). Contributors to functional changes were evaluated with multiple linear regression. Factors associated with the odds of progression from MCI to dementia longitudinally were evaluated with binary logistic regression. 1Florida Alzheimer's Disease Research Center. Cross-sectional analyses included 378 older adults classified as CNAD- (N = 76, age 66.1 ± 7.2, 63.2% female, 23.7% non-Hispanic/White), MCIAD- (N = 198, age 68.9 ± 7.9, 51.5% female, 29.3% non-Hispanic/White), or MCIAD+ (N = 104, age 73.9 ± 7.4, 52.9% female, 49.0% non-Hispanic/White). Longitudinal analyses focused on 207 participants with MCI (68.5% of cross-sectional MCI sample) followed for an average of 3 years. Demographics (age, sex, years of education, self-identified race and ethnicity, primary spoken language), National Alzheimer's Coordinating Center-defined clinical phenotypes (Clinically Normal, Impaired - Not MCI, Amnestic MCI, Nonamnestic MCI, Dementia), recruitment source (clinic-based versus community-based), genetics (APOE genotype), functional evaluation (Clinical Dementia Rating scale), global cognition (Mini Mental State Exam), vascular history (Vascular Burden Score), neuropsychiatric symptoms (NPI-Q Total score), plasma biomarkers (ALZPath p-tau217, Quanterix Simoa-based GFAP and NfL), and brain imaging (grey matter volume in select AD-relevant regions of interest, global white matter hyperintensity volume). Among those with MCI, 104 (34.4%) had plasma biomarker evidence of AD. MCIAD+ participants were more frequently recruited from clinic-based settings than MCIAD- (74.8% vs. 47.5%, p<.001). Over half (51.5%) of MCIAD+ carried at least one APOE e4 allele compared to 26.6% of MCIAD- and 29.4% of CNAD- (p<.001). Both MCIAD+ (p<.001, Cohen's d = 0.93) and MCIAD- (p<.001, d = 0.75) reported more severe neuropsychiatric symptoms than CNAD. MCIAD+ had higher plasma GFAP and NfL than both MCIAD- (GFAP: p<.001, d = 0.88, NfL: p<.001, d = 0.86) and CNAD- (GFAP: p<.001, d = 0.80; NfL: p<.001, d = 0.89). For the AD signature region of interest, MCIAD+ had lower volume than both CNAD- (p<.001, d = 0.78) and MCIAD- (p=.018, d = 0.39). For the hippocampus, both MCIAD+ (p<.001, d = 0.87) and MCIAD- (p<.001, d = 0.64) had lower volume than CNAD-. Longitudinally, older age (OR=1.14 [1.06-1.22], p<.001), higher levels of p-tau217 (OR=10.37 [3.00-35.02], p<.001) and higher neuropsychiatric symptoms (OR=1.19 [1.02-1.39], p=.023) were associated with higher odds of progression to dementia. MCI is etiologically heterogeneous. The presence of Alzheimer's pathology defined by elevated plasma p-tau217 in individuals with MCI significantly worsens prognosis. Neuropsychiatric symptoms may contribute to cognitive complaints and risk for progressive decline irrespective of AD pathology. Plasma p-tau217 can inform our understanding of base rates of different MCI phenotypes on a larger scale. As with other AD biomarkers, frequency of elevated plasma p-tau217 and odds of progression to dementia requires careful consideration of recruitment source (clinic- vs. community-based), especially across ethno-racially diverse older adults. Ongoing integration of emerging neurodegenerative disease biomarkers with detailed clinical evaluations will continue to improve treatment specificity and prognosis.

Amyloid profile is associated with sleep quality in preclinical but not in prodromal Alzheimer’s disease older adults

BackgroundFew studies have assessed whether neuropathological markers of AD in the preclinical and prodromal stages are associated with polysomnographic changes and obstructive sleep apnea (OSA). MethodsThis was a cross-sectional, case-control study of older adults (≥60 years) without relevant clinical and psychiatric comorbidities selected randomly from a cohort of individuals without dementia in a tertiary university hospital in São Paulo, Brazil. They underwent neuropsychological evaluation for clinical diagnosis and were allocated into two samples: cognitively unimpaired (CU) and mild cognitive impairment (MCI). Also, they underwent PET-PiB to determine the amyloid profile and all-night in-lab polysomnography. For each sample, we compared polysomnographic parameters according to the amyloid profile (A+ vs A-). ResultsWe allocated 67 participants (mean age 73 years, SD 10,1), 70 % females, 14 ± 5 years of education, into two samples: CU (n = 28, 42.4 %) and MCI (n = 39, 57.6 %). In the CU sample, the group A+ (n = 9) showed worse sleep parameters than A- (n = 19) (lower total sleep time (p = 0.007), and sleep efficiency (p = 0.005); higher sleep onset latency (p = 0.025), wake time after sleep onset (p = 0.011), and arousal index (AI) (p = 0.007)), and changes in sleep structure: higher %N1 (p = 0.005), and lower %REM (p = 0.006). In the MCI sample, MCI A-had higher AI (p = 0.013), respiratory disturbance index (p = 0.025, controlled for age), and higher rates of severe OSA than A+. DiscussionThe amyloid profile was associated with polysomnographic markers of worse sleep quality in individuals with preclinical AD but not with prodromal AD, probably due to the higher frequencies of severe OSA.

Ketogenic Dietary Effects on Sleep, Cognition and Behavior in MCI: Baseline Sleep Results

AbstractBackgroundSleep disturbances in dementia occur often, are reported as neuropsychiatric symptoms, and are associated with higher caregiver burden and institutionalization. In mild cognitive impairment (MCI), sleep changes co‐occur with increasing neuropsychiatric symptoms and cognitive decline. Diet quality, like sleep, is a modifiable risk factor for Alzheimer’s disease. It is unknown how dietary interventions may impact sleep quality. This controlled clinical trial investigates for the first time a modified Mediterranean ketogenic diet (MMKD) compared to a low‐fat American Heart Association diet (AHAD) over 4 months on multiple sleep indices in adults with amnestic MCI. Here we report our baseline sleep findings.MethodThe WatchPAT Central Plus, an FDA approved home sleep test, was used to assess sleep quality. The WatchPAT quantifies numerous measures including total sleep time, pulse and sleep efficiency. Sleep‐disordered breathing is measured via the apnea‐hypopnea index (AHI) and oxygen‐desaturation index (ODI). Time spent in sleep stages is also quantified along with full night oxygen saturation and pulse rate. Independent samples t‐tests compared baseline sleep differences among male and female MCI participants.ResultA total of 64 MCI participants completed the baseline sleep assessments (mean age 70.2±7.0, BMI 27.0±4.3; 64.1% women). Mean sleep duration was 6 hrs46 min and 83.9% sleep efficiency. Mean AHI was 17.3±12.2 and mean ODI was 8.2±7.5 measured as &gt;3% 02 desaturations, indicating on average moderate severity sleep apnea (AHI&gt;15). Overnight sleep percentage by sleep stage (estimated from heart rate and accelerometer) averaged 15.4% in deep sleep and 22.3% in REM sleep. Mean REM latency was 105 minutes. Oxygen saturation averaged 94% and pulse, 61 bpm. Women had higher resting pulse (64.3bpm, p&lt;.001). Sleep measures did not significantly differ by sex.ConclusionThe MCI sample, on average, had moderate severity sleep apnea at baseline, with sleep duration and efficiency slightly below standard recommendations of 7‐8 hours and efficiency &gt; 85%, respectively. Future work will compare longitudinal changes in sleep quality across diet intervention groups. Understanding potential therapeutic effects of the MMKD on sleep quality and cognitive change will be vital in adding to the portfolio of targeted non‐pharmacological interventions for Alzheimer’s disease prevention.

Neuropsychological change in Mild Cognitive Impairment using estimated standardized regression‐based formulas

AbstractBackgroundNeuropsychological change in Mild Cognitive Impairment (MCI) can be tracked with repeated assessments to determine if an individual remains stable or progresses to dementia. However, few studies have quantified these cognitive changes over time, especially using standardized regression‐based (SRB) change formulae.MethodParticipants included 283 MCI patients from a cognitive disorders clinic who were assessed twice with a comprehensive neuropsychological battery across approximately one‐ and one‐half years. SRB z‐scores were calculated for each of 17 test scores this battery for each participant. Change on these 17 z‐scores were examined for the entire sample, as well as between two subgroups: those who remained MCI on follow‐up (i.e., MCI‐Stable) and those who progressed to dementia (i.e., MCI‐Decline).ResultFor the entire MCI sample, significant declines were observed on all 17 z‐scores (p&lt;0.001), with the largest declines occurring on memory tests. When the two subgroups were compared, significant differences were observed between these two groups across nearly all cognitive domains, with the largest differences being on tests of attention and processing speed. For these group differences, those in the MCI‐Decline group showed the most decline compared to the MCI‐Stable participants. However, notable cognitive decline was also observed in the MCI‐Stable group.ConclusionThis study highlights the degree of cognitive decline that occurs in MCI across time, even among those who remain “stable” on follow‐up. It also highlights the value of the SRB method in more accurately capturing and quantifying cognitive decline, which may help identify individuals most vulnerable to MCI progression.

Applicability of an actuarial neuropsychological method to diagnose mild cognitive impairment in a diverse sample

AbstractBackgroundThe Jak/Bondi actuarial neuropsychological method for detection of mild cognitive impairment (MCI) has been shown to identify subjects less likely to revert to normal and more likely to have Alzheimer’s Disease (AD) biomarkers compared to conventional clinical methods. Various iterations of this method have been applied to datasets of predominately White, highly‐educated participants, limiting generalizability to more diverse cohorts. This project investigated the applicability of the actuarial MCI diagnostic method to the Texas Alzheimer’s Research and Care Consortium (TARCC) cohort.MethodAll subjects from the TARCC cohort with expert consensus diagnoses of normal control (NC) and MCI at baseline (n = 1911; 65.72% female; 47.11% Hispanic; Mage = 67.49; Medu = 12.80) were re‐classified as NC or MCI using actuarial criteria of 2 impaired (&gt;1 SD below normative mean) tests in any of 4 cognitive domains OR 1 impaired test in at least 3 cognitive domains. The clinically‐diagnosed MCI (MCIc) sample (n = 655; 58.47% female; 42.44% Hispanic; Mage = 71.34; Medu = 13.01) and the actuarially‐diagnosed MCI (MCIa) sample (n = 837; 71.21% female; 68.82% Hispanic; Mage = 66.30; Medu = 10.87) were separately submitted to cluster analysis. McNemar’s test was used to investigate frequency of APOE4 allele by diagnostic group.ResultCluster analysis of the MCIa group yielded 3 distinct clusters: a purely amnestic cluster (n = 332), a primary language‐impaired cluster (n = 381), and a multidomain/mixed cluster (n = 124). The MCIc group yielded 2 clusters: a multidomain/mixed cluster (n = 538), and a cognitively normal cluster (n = 117). The MCIc cases were significantly more likely to have APOE4 alleles (33% vs. 28% of MCIa group).ConclusionSimilar to previous research, the MCIa group fell into 3 distinct cognitively‐impaired groups. Despite 18% of MCIc participants falling in a “cognitively‐normal” cluster, MCIc subjects were more likely to have the AD biomarker APOE4. These findings warrant further investigation, particularly in relation to ethnicity, as individuals of Hispanic origin are less likely to carry APOE4 alleles, and APOE4 confers less AD risk in Hispanics compared to non‐Hispanic Whites. Future research will investigate the prognostic utility of the actuarial method for racial/ethnic minorities using cognitive and functional longitudinal data.

The effect of Mild Cognitive Impairment (MCI) on psychological distress among older adults in Ukraine

ObjectivesUnderstanding the negative consequences of Mild Cognitive Impairment (MCI) in Ukraine among a population who have collectively experienced difficult life events, provided the impetus for the current study which analyzed whether the perception of psychological distress differed among older adults with two types of MCI (amnestic MCI [aMCI] & nonamnestic MCI [naMCI]) compared to their cognitively intact peers.MethodA sample of 132 older adults were selected from an outpatient regional hospital in Lviv, Ukraine and assigned into either an MCI or non-MCI control group. A demographic survey, and the Symptom Questionnaire (SQ) were administered to both groups.ResultsResults of an ANOVA comparing the SQ sub-scales between the Ukrainian MCI and control groups were analyzed. A multiple hierarchical regression analysis assessed the predictive value of MoCA scores on the SQ sub-scales. Compared to adults in the MCI group, adults in the control group reported significantly lower rates of anxiety, somatic, depressive symptoms, and total psychological distress.DiscussionWhile the level of cognitive impairment was a significant predictor for each sub-type of distress, the explained variance was minimal suggesting that other factors also played a role. Reference was made to a similar MCI sample in the U.S. which had lower SQ psychological distress scores than the Ukraine sample, further suggesting possible environmental effects on symptoms. The importance of depression and anxiety screening and treatment for older adults with MCI was also discussed.

Psychosocial profiles within community-dwelling older adults with Mild Cognitive Impairment: A prevalence and latent profile analysis study.

Mild Cognitive Impairment (MCI) is an at-risk stage for dementia and accurate prevalence studies are lacking in Singapore. From the literature, it is evident that psychosocial factors increase the risk of conversion to dementia. In this study, we sought to establish the prevalence of MCI in Singapore and study the associated psychosocial factors using latent profile analysis. 902 community-dwelling older adults, aged between 60 and 99 years old (Mage = 70.48 years), were recruited as part of the Community Health and Intergenerational Study (CHI). They completed neurocognitive assessments and questionnaires on depression and anxiety symptoms, quality of life, social support, satisfaction with life, and social connectivity. Petersen's criteria was used to diagnose MCI. Within the MCI sample, 166 subjects' psychosocial scores were entered into a latent profile analysis to identify profiles of psychosocial functioning. The prevalence of MCI in our sample was 21.5%. They had significantly lower years of education and perceived social support and higher depressive symptoms than the normal ageing group. Three distinct profiles emerged within the MCI group corresponding to a positive (45.2%), neutral (38.5%), and negative (16.3%) pattern of psychosocial scores. These profiles did not differ significantly in terms of demographic or cognitive variables. The three psychosocial profiles might reflect the differing implications of MCI on a person's well-being and the negative psychosocial profile might likely be most at risk of conversion to dementia. Future longitudinal studies are required to confirm these implications.

Sex-specific differences in neuropsychological profiles of mild cognitive impairment in a hospital-based clinical sample.

Mild cognitive impairment (MCI) is an etiologically nonspecific diagnosis including a broad spectrum of cognitive decline between normal aging and dementia. Several large-scale cohort studies have found sex effects on neuropsychological test performance in MCI. The primary aim of the current project was to examine sex differences in neuropsychological profiles in a clinically diagnosed MCI sample using clinical and research diagnostic criteria. The current study includes archival data from 349 patients (age M = 74.7; SD = 7.7) who underwent an outpatient neuropsychological evaluation and were diagnosed with MCI. Raw scores were converted to z-scores using normative datasets. Sex differences in neurocognitive profiles including severity, domain-specific composites (memory, executive functioning/information processing speed, and language), and modality-specific learning curves (verbal, visual) were examined using Analysis of Variance, Chi-square analyses, and linear mixed models. Post hoc analyses examined whether sex effects were uniform across age and education brackets. Females exhibit worse non-memory domain and test-specific cognitive performances compared to males with otherwise comparable categorical MCI criteria and global cognition measured via screening and composite scores. Analysis of learning curves showed additional sex-specific advantages (visual Males>Females; verbal Females >Males) not captured by MCI subtypes. Our results highlight sex differences in a clinical sample with MCI. The emphasis of verbal memory in the diagnosis of MCI may result in diagnosis at more advanced stages for females. Additional investigation is needed to determine whether these profiles confer greater risk for progressing to dementia or are confounded by other factors (e.g., delayed referral, medical comorbidities).

A graph theoretic approach to neurodegeneration: five data-driven neuropsychological subtypes in mild cognitive impairment

ABSTRACT Mild cognitive Impairment (MCI) is notoriously heterogenous in terms of clinical presentation, neuroimaging correlates, and subsequent progression. Predicting who will progress to dementia, which type of dementia, and over what timeframe is challenging. Previous work has attempted to identify MCI subtypes using neuropsychological measures in an effort to address this challenge; however, there is no consensus on approach, which may account for some of the variability. Using a hierarchical community detection approach, we examined cognitive subtypes within an MCI sample (from the Alzheimer’s Disease Neuroimaging Initiative [ADNI] study). We then examined whether these subtypes were related to biomarkers (e.g., cortical volumes, fluorodeoxyglucose (FDG)-positron emission tomography (PET) hypometabolism) or clinical progression. We identified five communities (i.e., cognitive subtypes) within the MCI sample: 1) predominantly memory impairment, 2) predominantly language impairment, 3) cognitively normal, 4) multidomain, with notable executive dysfunction, 5) multidomain, with notable processing speed impairment. Community membership was significantly associated with 1) cortical volume in the hippocampus, entorhinal cortex, and fusiform cortex; 2) FDG PET hypometabolism in the posterior cingulate, angular gyrus, and inferior/middle temporal gyrus; and 3) conversion to dementia at follow up. Overall, community detection as an approach appears a viable method for identifying unique cognitive subtypes in a neurodegenerative sample that were linked to several meaningful biomarkers and modestly with progression at one year follow up.

A Direct Comparison of 10 WAIS-IV Digit Span Embedded Validity Indicators among a Mixed Neuropsychiatric Sample with Varying Degrees of Cognitive Impairment.

Reliable Digit Span (RDS), RDS-Revised (RDS-R), and age-corrected scaled score (ACSS) have been previously validated as embedded performance validity tests (PVTs) from the Wechsler Adult Intelligence Scale-IV Digit Span subtest (WAIS-IV DS). However, few studies have directly compared the relative utility of these and other proposed WAIS-IV DS validity indicators within a single sample. This study compared classification accuracies of 10 WAIS-IV DS indices in a mixed neuropsychiatric sample of 227 outpatients who completed a standardized neuropsychological battery. Participants with ≤1 PVT failures of the four, freestanding criterion PVTs constituted the valid group (n = 181), whereas those with ≥2 PVT failures formed the invalid group (n = 46). Among the valid group, 113 met criteria for mild cognitive impairment (MCI). Classification accuracies for all DS indicators were statistically significant across the overall sample and subsamples with and without MCI, apart from indices derived from the Forward trial in the MCI sample. DS Sequencing ACSS, working memory RDS (wmRDS), and DS ACSS emerged as the most effective predictors of validity status, with acceptable to excellent classification accuracy for the overall sample (AUCs = 0.792-0.816; 35%-50% sensitivity/88%-96% specificity). Although most DS indices demonstrated clinical utility as embedded PVTs, DS Sequencing ACSS, wmRDS, and DS ACSS may be particularly robust to cognitive impairment, minimizing risk of false positive errors while identifying noncredible performance. Moreover, DS indices incorporating data from multiple trials (i.e., wmRDS, DS ACSS) also generally yielded greater classification accuracy than those derived from a single trial.

Practice Effects in Mild Cognitive Impairment Increase Reversion Rates and Delay Detection of New Impairments.

ObjectiveCognitive practice effects (PEs) can delay detection of progression from cognitively unimpaired to mild cognitive impairment (MCI). They also reduce diagnostic accuracy as suggested by biomarker positivity data. Even among those who decline, PEs can mask steeper declines by inflating cognitive scores. Within MCI samples, PEs may increase reversion rates and thus impede detection of further impairment. Within an MCI sample at baseline, we evaluated how PEs impact prevalence, reversion rates, and dementia progression after 1 year.MethodsWe examined 329 baseline Alzheimer’s Disease Neuroimaging Initiative MCI participants (mean age = 73.1; SD = 7.4). We identified test-naïve participants who were demographically matched to returnees at their 1-year follow-up. Since the only major difference between groups was that one completed testing once and the other twice, comparison of scores in each group yielded PEs. PEs were subtracted from each test to yield PE-adjusted scores. Biomarkers included cerebrospinal fluid phosphorylated tau and amyloid beta. Cox proportional models predicted time until first dementia diagnosis using PE-unadjusted and PE-adjusted diagnoses.ResultsAccounting for PEs increased MCI prevalence at follow-up by 9.2% (272 vs. 249 MCI), and reduced reversion to normal by 28.8% (57 vs. 80 reverters). PEs also increased stability of single-domain MCI by 12.0% (164 vs. 147). Compared to PE-unadjusted diagnoses, use of PE-adjusted follow-up diagnoses led to a twofold increase in hazard ratios for incident dementia. We classified individuals as false reverters if they reverted to cognitively unimpaired status based on PE-unadjusted scores, but remained classified as MCI cases after accounting for PEs. When amyloid and tau positivity were examined together, 72.2% of these false reverters were positive for at least one biomarker.InterpretationEven when PEs are small, they can meaningfully change whether some individuals with MCI retain the diagnosis at a 1-year follow-up. Accounting for PEs resulted in increased MCI prevalence and altered stability/reversion rates. This improved diagnostic accuracy also increased the dementia-predicting ability of MCI diagnoses.

Accounting for practice effects improves stability of MCI diagnosis and uncovers new impairments

AbstractBackgroundWe previously showed that failure to account for practice effects (PEs) delays detection of conversion from unimpaired to mild cognitive impairment (MCI) and reduces diagnostic accuracy based on biomarker positivity data. Even among those who decline, PE can mask steeper declines by inflating cognitive scores. Within MCI samples, PEs may increase reversion rates and impede detection of new impairments. Here, within a baseline MCI sample, we evaluated how PEs affect prevalence, reversion rates, and progression from single‐domain to multi‐domain MCI at follow‐up.MethodWe examined 347 baseline Alzheimer’s Disease Neuroimaging Initiative MCI participants (mean age=73.2; SD=7.4). We used Jak/Bondi diagnostic criteria (6 tests). We also calculated PEs on a cognitive composite (ADAS‐cog 11) and a cognitive screener (MMSE). We identified participants who were demographically matched to returning subjects at their 1‐year follow‐up. The only difference was that one group was tested once and the other had completed prior testing. We subtracted PEs—based on comparing these groups—from follow‐up scores and recalculated MCI diagnoses.ResultPEs were absent or small for 5 tests (Cohen’s d=.00‐.06) and medium for 1 (d=.50). There was a PE on the MMSE (Cohen’s d =.16), but none was found on the ADAS‐cog 11. Accounting for PEs increased MCI prevalence at follow‐up by 6% (252 vs 268), and reduced reversion rate by 15% (95 vs 79). PEs also masked progression from single‐domain to multi‐domain MCI: 24 vs 36 (+50.0% after accounting for PEs).ConclusionAlthough PEs were small, accounting for them in baseline MCI participants after 1‐year, increased MCI prevalence and progression from single‐domain to multi‐domain, and decreased reversion rates. PEs may be masked within a composite measures, but were present on a short cognitive screener. Failure to consider PEs reduces accuracy regarding conclusions about MCI stability/change and weakens our ability to determine when impairment spreads to new domains.

A Game a Day Keeps Cognitive Decline Away? A Systematic Review and Meta-Analysis of Commercially-Available Brain Training Programs in Healthy and Cognitively Impaired Older Adults.

The rising prevalence rates of age-related cognitive impairment are a worldwide public concern, bringing about a surge in the number of "brain training" programs commercially available to the general public. Numerous companies advertise that their products improve memory and protect against cognitive decline, though researchers have voiced concerns regarding the validity of such claims. To address this issue, the current meta-analytic investigation examined evidence from 43 studies (encompassing 2,636 participants) to evaluate the efficacy of commercial training programs within two separate populations: healthy older adults and older adults with mild cognitive-impairment (MCI). Seven programs were identified: BrainGymmer, BrainHQ, CogMed, CogniFit, Dakim, Lumosity, and MyBrainTrainer. Analyses yielded small, significant near-transfer effects for both healthy and MCI samples. Far-transfer was not observed for the MCI sample, whereas a small, significant effect was found for subjective but not objective measures of far-transfer in the healthy sample. Analyses of individual domains (combining near-and far-transfer outcomes) yielded significant transfer to executive-functioning, memory, and processing-speed in healthy older adults. After adjusting for publication bias, only the effect size for processing speed remained significant. Transfer to attention, objective everyday functioning, fluid-intelligence, and visuospatial domains was not significant. Thus, whilst "brain training" may be suitable for enjoyment and entertainment purposes, there is currently insufficient empirical evidence to support that such training can improve memory, general cognition, or everyday functioning. This area of research is still in its infancy and warrants further investigation to provide more substantial evidence regarding the efficacy of this rapidly expanding industry.

Longitudinal changes on the Independent Living Scale in amnestic mild cognitive impairment

The Independent Living Scales (ILS) is an objective measure of day-to-day functioning, which can be used to aid in diagnosing dementia in older adults with cognitive impairments. However, no studies have examined this measure longitudinally in individuals with mild cognitive impairment (MCI), a prodromal phase of dementia. Three subscales of the ILS (Managing Money, Managing Home and Transportation, Health and Safety) were administered to a sample of 94 individuals with amnestic MCI twice across 15 months. A measure of global cognition (Total Scale score on the Repeatable Battery for the Assessment of Neuropsychological Status [RBANS]) was also administered twice. In this MCI sample, two of the three subscales of the ILS showed a significant decline over time, where the third ILS subscale and the Total Scale score of the RBANS did not change. Regression-based change models showed that baseline ILS scores were most strongly predictive of follow-up ILS scores compared to RBANS scores at baseline and follow-up and demographic variables (age, education, and sex). These results provide additional information on the longitudinal change on the ILS in a sizeable cohort of older individuals with amnestic MCI, which may make this scale more useful in identifying progression to dementia.

Regression‐based normative data for the Rey Auditory Verbal Learning Test in Norwegian and Swedish adults ages 40 to 80

AbstractBackgroundAdequate memory assessment is important in neuropsychological evaluation of middle‐aged and older adults with suspected mild cognitive impairment (MCI) and/or Alzheimer’s disease. The Rey Auditory Verbal Learning Test (RAVLT) is a widely used measure of episodic verbal memory. To our knowledge, culturally adapted and demographically adjusted normative data for the RAVLT are currently not available for Scandinavian adults. The objective of this study was to develop regression‐based norms for the Rey Auditory Verbal Learning Test (RAVLT) for Scandinavian adults aged 40 to 80 years. We also test the validity and demographic adjustment of these norms in a clinical sample of participants with mild cognitive impairment.MethodsParticipants were cognitively normal healthy controls from the Norwegian Dementia Disease Initiation cohort (n=72), and the Swedish Gothenburg MCI study (n=124). Using a regression‐based norming procedure, we estimated effects of age, gender and years of education on RAVLT test scores. The newly developed norms were applied in an independent sample of adults with MCI (n=59) from the DDI cohort, and we compared performance between the two groups using independent t‐tests.ResultsLower age, female gender and more years of education predicted higher performance on the RAVLT. The norms successfully adjusted for the demographic variables in the MCI sample, and performance was significantly higher in the healthy control group (p&lt;.001).ConclusionWe propose regression‐based norms the RAVLT adjusting for the effects of age, gender and education. The norms may be used for assessment of Norwegian and Swedish adults between the ages of 40 and 80 years, with between 6 and 22 years of education.

A-02 Comparing Rate of Change in MoCA and MMSE Scores Over Time in an MCI and AD sample

Abstract Objective The Montreal Cognitive Assessment (MoCA) and Mini-Mental Status Exam (MMSE) are used for tracking cognitive change in mild cognitive impairment (MCI) and Alzheimer’s disease (AD), despite limited empirical support for this purpose. This study compared longitudinal change in MMSE and MoCA scores to investigate their applicability for tracking cognitive change. Method Inclusion criteria were: diagnosis of MCI or AD (CDR global = .5) by consensus conference, administration of the MoCA and MMSE across ≥3 visits, and no reversion to normal (n = 59; Mage = 70.81; Meducation = 14.97; 56% male; 76.3% Caucasian; 80% MCI at baseline). Testing sessions occurred ~ 12 months apart (M = 12.59, SD = 3.43, range 5–28 months). Change in MMSE and MoCA scores was modeled using multilevel regression. A 95% bootstrap confidence interval (BCI) for the slopes of both tests was computed and used to evaluate whether the tests measured significantly different change. Results Controlling for age and education, the MoCA demonstrated significantly more change over time (95% BCI [−0.06, −0.02]; MoCA Visit 1 M = 24.00, Visit 4 M = 21.88) than the MMSE (95% BCI [−0.03, 0.01]; MMSE Visit 1 M = 27.83, Visit 4 M = 27.50). MoCA scores significantly declined over the study period (but did not exceed the reliable change index), while MMSE scores did not. Conclusions The MMSE did not show significant change over time, while the MoCA did in this heavily MCI sample. Although statistically significant, clinical significance of change in the MoCA is unclear. Increasing MoCA use calls for additional research to understand what constitutes a clinically significant change and whether it is appropriate for tracking cognitive trajectories.

Validation of one-year reliable change in the RBANS for community-dwelling older adults with amnestic mild cognitive impairment

Objective The current study sought to externally validate previously published standardized regression-based (SRB) equations for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Indexes administered twice over a one-year period. Method: Hammers and colleagues’ SRB prediction equations were applied to two independent samples of community-dwelling older adults with amnestic Mild Cognitive Impairment (MCI), including those recruited from the community (n = 64) and those recruited from a memory disorders clinic (n = 58). Results: While Observed Baseline and Observed Follow-up performances were generally comparable for both MCI samples over one year, both samples possessed significantly lower Observed One-Year Follow-up scores than were predicted based on Hammers and colleagues' development sample across many RBANS Indexes. Relatedly, both amnestic MCI samples possessed a greater percentage of participants either “declining” or failing to exhibit a long-term practice effect over one year relative to expectation across most Indexes. Further, the clinic-recruited amnestic MCI sample displayed worse baseline performances, smaller long-term practice effects, and greater proportions of individual participants exhibiting a decline across one year relative to the community amnestic MCI sample. Conclusions: These findings validate Hammers and colleagues' SRB prediction equations by (1) indicating their ability to identify clinically meaningful change across RBANS Indexes in independent samples, and (2) discriminating rates of cognitive change among cognitively nuanced samples.

The independent living scale in amnestic mild cognitive impairment: Relationships to demographic variables and cognitive performance

ABSTRACT Introduction The Independent Living Scales (ILS) is an objective measure of day-to-day functioning, which can be used to aid in diagnosing dementia in older adults with cognitive impairments. However, no studies have examined this measure in individuals with Mild Cognitive Impairment (MCI), a prodromal phase of dementia. Method Therefore, we sought to examine three subscales of the ILS (Managing Money, Managing Home and Transportation, Health and Safety) in a sample of 132 individuals with amnestic MCI, focusing on the relationship of the ILS with demographic variables (age, education, sex) and cognitive abilities (assessed with the Repeatable Battery for the Assessment of Neuropsychological Status [RBANS]). Results This MCI sample showed intact daily functioning on the three ILS subscales. In a series of three, separate hierarchical linear regression models, the Managing Money, Managing Home and Transportation, and Health and Safety subscales were all significantly related to demographic variables, and the RBANS Total Scale score significantly added to all models. These models would also allow one to predict an ILS score based on demographic and cognitive data, which could be compared to an observed ILS score to see if it meets expectations. Conclusions Overall, these results indicate that daily functioning, as measured with the ILS, is related to cognitive abilities in amnestic MCI, and that demographic variables also influenced ILS scores in this cohort. Although the ILS may be appropriate for identifying functional abilities in MCI, the consideration of these moderating variables seems necessary.

Patterns of longitudinal cortical atrophy over 3 years in empirically derived MCI subtypes

We previously identified 4 empirically derived mild cognitive impairment (MCI) subtypes via cluster analysis within the Alzheimer's Disease Neuroimaging Initiative (ADNI) and demonstrated high correspondence between patterns of cortical thinning at baseline and each cognitive subtype. We aimed to determine whether our MCI subtypes demonstrate unique longitudinal atrophy patterns. ADNI participants (295 with MCI and 134 cognitively normal [CN]) underwent annual structural MRI and neuropsychological assessments. General linear modeling compared vertex-wise differences in cortical atrophy rates between each MCI subtype and the CN group. Linear mixed models examined trajectories of cortical atrophy over 3 years within lobar regions of interest. Compared to the CN group, those with amnestic MCI (memory deficit) initially demonstrated greater atrophy rates within medial temporal lobe regions that became more widespread over time. Those with dysnomic/amnestic MCI (naming/memory deficits) showed greater atrophy rates largely localized to temporal lobe regions. The mixed MCI (impairment in all cognitive domains) group showed greater atrophy rates in widespread regions at all time points. The cluster-derived normal group, who had intact neuropsychological performance and normal cortical thickness at baseline despite their MCI diagnosis via conventional diagnostic criteria, continued to show normal cognition and minimal cortical atrophy over 3 years. ADNI's purported amnestic MCI sample produced more refined cognitive subtypes with unique longitudinal cortical atrophy rates. These novel MCI subtypes reliably reflect underlying atrophy, reduce false-positive diagnostic errors, and improve prediction of clinical course. Such improvements have implications for the selection of participants for clinical trials and for providing more precise risk assessment for individuals diagnosed with MCI.

Social Cognition in Rehabilitation Context: Different Evolution of Affective and Cognitive Theory of Mind in Mild Cognitive Impairment.

Maintaining social skills such as Theory of Mind (ToM) competences is important to counteract the conversion into dementia in Mild Cognitive Impairment (MCI). Multidimensional nonpharmacological interventions demonstrated their potential in improving cognitive and behavioral abilities; however, little is known about the long-term effect of such interventions on social skills in people with MCI. The aim of this longitudinal study was to monitor ToM competences considering both cognitive and affective domains in an amnestic MCI (aMCI) sample involved in a home-based multistimulation treatment (MST@H). 30 aMCI subjects (M : F = 15 : 15; mean age ± SD = 77.00 ± 4.60) were enrolled, and three steps of evaluation with neuropsychological tests and ToM tasks have been implemented. 21 healthy controls (HC) were also included (M : F = 9 : 12; mean age ± SD = 74.95 ± 3.88) to characterize the aMCI sample regarding differences in ToM performance compared to HC at the baseline evaluation. Our results show that the aMCI group statistically significantly underperformed the HC group only in the advanced ToM tasks, confirming an initial decline of high-level ToM competences in this population. The longitudinal evaluation revealed time changes not only in some subcognitive domains of MoCA (memory and executive functions) but also in cognitive and affective ToM dimensions in aMCI subjects. Our findings suggest that cognitive and affective ToM can be considered useful outcome measures to test the long-term effect of treatment over time.