Dementia is characterized by impairments in an individual's cognitive and functional abilities. Digital cognitive assessments have been shown to be effective in detecting mild cognitive impairment and dementia, but whether they can stage the disease remains to be studied.

In this study, we examined (1) the correlation between scores obtained from BrainCheck standard battery of cognitive assessments (BC-Assess), a digital cognitive assessment, and scores obtained from the Dementia Severity Rating Scale (DSRS), and (2) the accuracy of using the BC-Assess score to predict dementia stage delineated by the DSRS score. We also explored whether BC-Assess can be combined with information from the Katz Index of Independence in activities of daily living (ADL) to obtain enhanced accuracy.

Retrospective analysis was performed on a BrainCheck dataset containing 1751 patients with dementia with different cognitive and functional assessments completed for cognitive care planning, including the DSRS, the ADL, and the BC-Assess. The patients were staged according to their DSRS total score (DSRS-TS): 982 mild (DSRS-TS 10-18), 656 moderate (DSRS-TS 19-26), and 113 severe (DSRS-TS 37-54) patients. Pearson correlation was used to assess the associations between BC-Assess overall score (BC-OS), ADL total score (ADL-TS), and DSRS-TS. Logistic regression was used to evaluate the possibility of using patients' BC-OS and ADL-TS to predict their stage.

We found moderate Pearson correlations between DSRS-TS and BC-OS (r=-0.53), between DSRS-TS and ADL-TS (r=-0.55), and a weak correlation between BC-OS and ADL-TS (r=0.37). Both BC-OS and ADL-TS significantly decreased with increasing severity. BC-OS demonstrated to be a good predictor of dementia stages, with an area under the receiver operating characteristic curve (ROC-AUC) of classification using logistic regression ranging from .733 to .917. When BC-Assess was combined with ADL, higher prediction accuracies were achieved, with an ROC-AUC ranging from 0.786 to 0.961.

Our results suggest that BC-Assess could serve as an effective alternative tool to DSRS for grading dementia severity, particularly in cases where DSRS, or other global assessments, may be challenging to obtain due to logistical and time constraints.

Executive dysfunction is characteristic of behavioral variant frontotemporal dementia (bvFTD) but can be challenging to detect. Dispersion-based intraindividual variability (IIV-d) is hypothesized to reflect a sensitive index of executive dysfunction and has demonstrated relevance to functional decline but has not been evaluated in bvFTD.

We report on 477 demographically matched participants (159 cognitively healthy [CH], 159 clinical Alzheimer's disease [AD], 159 clinical bvFTD/prodromal bvFTD) who completed the Uniform Data Set 3.0 Neuropsychological Battery. IIV-d was measured using the coefficient of variance (CoV; raw and demographically adjusted) across 12 Uniform Data Set 3.0 Neuropsychological Battery indicators and the informant-rated Functional Activities Questionnaire assessed daily functioning.

Analysis of covariance showed that participants in the bvFTD/prodromal bvFTD group exhibited higher raw and demographically adjusted CoV compared to CH participants, at a very large effect size (d = 1.28-1.47). Demographically adjusted (but not raw) CoV was lower in the bvFTD/prodromal bvFTD group than the AD group, though the effect size was small (d = .38). Both CoV metrics accurately differentiated the bvFTD/prodromal bvFTD and CH groups (areas under the curve = .84), but not bvFTD/prodromal bvFTD and AD groups (areas under the curve = .59). Regression analyses in the bvFTD/prodromal bvFTD group indicated that higher IIV-d on both metrics was associated with greater daily functioning impairment, over and above covariates.

Compared to healthy adults, individuals with bvFTD/prodromal bvFTD show greater levels of performance variability across a battery of neuropsychological measures, which interferes with everyday functioning. These data demonstrate the clinical utility and ecological validity of IIV-d in bvFTD/prodromal bvFTD, though these findings should be replicated in more diverse samples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

We investigated whether quantitative electroencephalography (qEEG) correlates with cognition and cortical superficial siderosis (cSS) in cerebral amyloid angiopathy.

We included patients with sporadic (sCAA) and hereditary Dutch-type CAA (D-CAA). Spectral measures and the phase lag index (PLI) were analyzed on qEEG. Cognition was assessed with the MoCA and cSS presence was scored on 3T-MRI. Linear regression analyses were performed to investigate these qEEG measures and cognition. Independent samples T-tests were used to analyze the qEEG measure differences between participants with and without cSS.

We included 92 participants (44 D-CAA; 48 sCAA). A lower average peak frequency (β[95 %CI] = 0.986[0.252-1.721]; P = 0.009) and a higher spectral ratio (β[95 %CI] = -0.918[-1.761--0.075]; P = 0.033) on qEEG correlated with a lower MoCA score, irrespective of a history of symptomatic intracerebral hemorrhage (sICH). The PLI showed no correlation to the MoCA. qEEG slowing was not different in those with or without cSS.

Spectral qEEG (but not PLI) reflects cognitive performance in patients with CAA with and without a history of sICH. We found no association between qEEG slowing and cSS.

qEEG could be a valuable biomarker, especially in challenging cognitive testing situations in CAA, and a potential predictive tool in future studies.

Methods of evaluating clinically meaningful decline are critical in research on Alzheimer's disease. A common method of quantifying clinically meaningful change is to calculate an anchor-based minimal clinically important difference (MCID) score. In this approach, individuals who report a meaningful change serve as the "anchors", and the mean level of change for this group serves as the MCID. In research on Alzheimer's disease, there are several possible anchors, including patients, knowledgeable observers (e.g., a family member), and clinicians. The goal of this study was to examine the extent to which agreement among anchors impacts MCID estimation and whether this relationship is moderated by cognitive severity status.

Analyses were completed on a longitudinal sample of 2247 adults, aged 50-103, from the Uniform Data Set. Outcome measures included the Montreal Cognitive Assessment, Clinical Dementia Rating-Sum of Boxes, and Functional Activities Questionnaire.

For all of the outcomes, the MCID estimate was significantly higher when meaningful decline was endorsed by all of the anchors compared to when there was disagreement among the anchors. In addition, the MCID estimate was higher with increasing severity of cognitive impairment. Finally, cognitive severity status moderated the influence of agreement among anchors on MCID estimation; as disease severity increased, anchor agreement demonstrated less influence on the MCID.

MCID estimates based on one anchor may underestimate meaningful change, and researchers should consider the viewpoints of multiple anchors in constructing MCIDs, particularly in the early stages of cognitive decline.

Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB.

The study sample included 97 participants with consensus-defined DLB from the National Alzheimer's Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual's performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual's performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ).

Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores).

Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.

A clinical diagnosis of Alzheimer's disease dementia (ADD) encompasses considerable pathological and clinical heterogeneity. While Alzheimer's disease patients typically show a characteristic temporo-parietal pattern of glucose hypometabolism on 18F-fluorodeoxyglucose (FDG)-PET imaging, previous studies have identified a subset of patients showing a distinct posterior-occipital hypometabolism pattern associated with Lewy body pathology. Here, we aimed to improve the understanding of the clinical relevance of these posterior-occipital FDG-PET patterns in patients with Alzheimer's disease-like amnestic presentations. Our study included 1214 patients with clinical diagnoses of ADD (n = 305) or amnestic mild cognitive impairment (aMCI, n = 909) from the Alzheimer's Disease Neuroimaging Initiative, who had FDG-PET scans available. Individual FDG-PET scans were classified as being suggestive of Alzheimer's (AD-like) or Lewy body (LB-like) pathology by using a logistic regression classifier trained on a separate set of patients with autopsy-confirmed Alzheimer's disease or Lewy body pathology. AD- and LB-like subgroups were compared on amyloid-β and tau-PET, domain-specific cognitive profiles (memory versus executive function performance), as well as the presence of hallucinations and their evolution over follow-up (≈6 years for aMCI, ≈3 years for ADD). Around 12% of the aMCI and ADD patients were classified as LB-like. For both aMCI and ADD patients, the LB-like group showed significantly lower regional tau-PET burden than the AD-like subgroup, but amyloid-β load was only significantly lower in the aMCI LB-like subgroup. LB- and AD-like subgroups did not significantly differ in global cognition (aMCI: d = 0.15, P = 0.16; ADD: d = 0.02, P = 0.90), but LB-like patients exhibited a more dysexecutive cognitive profile relative to the memory deficit (aMCI: d = 0.35, P = 0.01; ADD: d = 0.85 P < 0.001), and had a significantly higher risk of developing hallucinations over follow-up [aMCI: hazard ratio = 1.8, 95% confidence interval = (1.29, 3.04), P = 0.02; ADD: hazard ratio = 2.2, 95% confidence interval = (1.53, 4.06) P = 0.01]. In summary, a sizeable group of clinically diagnosed ADD and aMCI patients exhibit posterior-occipital FDG-PET patterns typically associated with Lewy body pathology, and these also show less abnormal Alzheimer's disease biomarkers as well as specific clinical features typically associated with dementia with Lewy bodies.

We examined the impact of conventional versus robust normative approaches on cognitive characterization and clinical classification of MCI versus dementia. The sample included participants from the National Alzheimer's Coordinating Center Uniform Data Set. Separate demographically adjusted z-scores for cognitive tests were derived from conventional (n = 4273) and robust (n = 602) normative groups. To assess the impact of deriving scores from a conventional versus robust normative group on cognitive characterization, we examined likelihood of having a low score on each neuropsychological test. Next, we created receiver operating characteristic (ROC) curves for the ability of normed scores derived from each normative group to differentiate between MCI (n = 3570) and dementia (n = 1564). We examined the impact of choice of normative group on classification accuracy by comparing sensitivity and specificity values and areas under the curves (AUC). Compared with using a conventional normative group, using a robust normative group resulted in a higher likelihood of low cognitive scores for individuals classified with MCI and dementia. Comparison of the classification accuracy for distinguishing MCI from dementia did not suggest a statistically significant advantage for either normative approach (Z = -0.29, p = .77; AUC = 0.86 for conventional and AUC = 0.86 for robust). In summary, these results indicate that using a robust normative group increases the likelihood of characterizing cognitive performance as low. However, there is not a clear advantage of using a robust over a conventional normative group when differentiating between MCI and dementia.

Cognitive fluctuations are characteristic of dementia with Lewy bodies (DLB) but challenging to measure. Dispersion-based intra-individual variability (IIV-d) captures neurocognitive performance fluctuations across a test battery and may be sensitive to cognitive fluctuations but has not been studied in DLB.

We report on 5,976 participants that completed the uniform data set 3.0 neuropsychological battery (UDS3NB). IIV-d was calculated via the intra-individual standard deviation across 12 primary UDS3NB indicators. Separate models using mean USD3NB score and the Montreal cognitive assessment (MoCA) total score tested the reproducibility of the incremental value of IIV-d over-and-above global cognition. Binary logistic regressions tested whether IIV-d could classify individuals with and without clinician-rated cognitive fluctuations. Multinomial logistic regressions tested whether IIV-d could differentiate participants with DLB, participants with Alzheimer's disease (AD), and participants with healthy cognition (CH), as well as the incremental diagnostic utility of IIV-d over-and-above clinician-rated cognitive fluctuations.

IIV-d exhibited large univariate associations with clinician-rated and non-clinician-informant reported cognitive fluctuations, which persisted when adjusting for MoCA but not the full battery mean. Of diagnostic relevance, greater IIV-d was consistently associated with DLB and AD relative to CH over-and-above global cognition and clinician-rated cognitive fluctuations. Greater IIV-d was less consistently associated with an increased probability of DLB relative to AD when controlling for global cognition.

IIV-d accurately differentiates DLB from CH over-and-above global cognition and clinician-rated cognitive fluctuations. IIV-d may supplement a thorough clinical interview of cognitive fluctuations and serve as a standardized performance-based indicator of this transdiagnostic phenomenon. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The aim was to set syndrome stage-specific (eg, cognitively unimpaired, severe dementia) metrics for functional change.

We selected 18,097 individuals who participated in 2 National Alzheimer's Coordinating Center visits between June 2005 and May 2020, with completed collateral rating of functioning on activities of daily living assessed by the Functional Activities Questionnaire.Both distribution-based (ie, regression-based reliable change indices) and anchor-based (ie, typical change associated with advancing a syndromal stage for clinically meaningful difference) methods were applied for individuals classified as: unimpaired cognition, mild cognitive impairment, mild dementia, moderate dementia, or severe dementia.

There were marked differences in the distribution of functional ratings depending on their syndromal stage. There were also differences in the functional change associated with advancing across different syndromal stages. These informed stage-specific metrics for reliable change indices and clinically meaningful differences.

Our indices provide a hitherto unavailable method that allows clinicians to determine whether observed functional change is reliable or meaningful based on syndromal stage.