Normative neuropsychological data are essential for interpretation of test performance in the context of demographic factors. The Mayo Normative Studies (MNS) aim to provide updated normative data for neuropsychological measures administered in the Mayo Clinic Study of Aging (MCSA), a population-based study of aging that randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. We examined demographic effects on neuropsychological measures and validated the regression-based norms in comparison to existing normative data developed in a similar sample.

The MNS includes cognitively unimpaired adults ≥30 years of age (n = 4,428) participating in the MCSA. Multivariable linear regressions were used to determine demographic effects on test performance. Regression-based normative formulas were developed by first converting raw scores to normalized scaled scores and then regressing on age, age2, sex, and education. Total and sex-stratified base rates of low scores (T < 40) were examined in an older adult validation sample and compared with Mayo’s Older Americans Normative Studies (MOANS) norms.

Independent linear regressions revealed variable patterns of linear and/or quadratic effects of age (r2 = 6–27% variance explained), sex (0–13%), and education (2–10%) across measures. MNS norms improved base rates of low performance in the older adult validation sample overall and in sex-specific patterns relative to MOANS.

Our results demonstrate the need for updated norms that consider complex demographic associations on test performance and that specifically exclude participants with mild cognitive impairment from the normative sample.

Despite recent advances in cross-cultural neuropsychological test development, suitable tests for cross-linguistic assessment of language functions are not widely available. The aims of this study were to develop and validate a brief naming test, the Copenhagen Cross-Linguistic Naming Test (C-CLNT), for the assessment of culturally, linguistically, and educationally diverse older adult populations in Europe.

The C-CLNT was based on a set of standardized color drawings. Items for the C-CLNT were selected by considering name agreement and frequency across five European and two non-European languages. Ambiguities in some of the selected items and scoring criteria were resolved after pilot testing in 10 memory clinic patients. The final 30-item C-CLNT was validated by verifying its psychometric properties in 24 controls and 162 diverse memory clinic patients with affective disorder, mild cognitive impairment, and with dementia.

The C-CLNT had acceptable scale reliability (coefficient alpha = .67) and good construct validity, with moderate to strong correlations with traditional language tests (r = .42– .75). Diagnostic accuracy for dementia was good and significantly better than that of the Boston Naming Test (areas under the curve of .80 vs .64, p < .001), but was poor for mild cognitive impairment. Only 3% of the variance in C-CLNT test scores was explained by immigrant background, while 6% was explained by age and years of education. In comparison, these proportions were 34 and 22% for the BNT.

The C-CLNT has promising clinical utility for cross-linguistic assessment of naming impairment in culturally, linguistically, and educationally diverse older adults.

Subjective cognitive decline (SCD) and how much cognitive decline impacts one’s ability to perform instrumental activities of daily living (iADLs) are necessary elements of neuropsychological assessment when diagnosing mild cognitive impairment (MCI) and dementia. Though limited, the literature suggests that culture and self-appraisal of cognitive abilities are related. However, it is unclear if differences exist in the subjective elements of neuropsychological assessments between patients born in Anglosphere countries (Canada, the USA, and the UK) versus immigrants born elsewhere (International Group).

We conducted a retrospective chart review of advanced Parkinson’s disease (PD) patients (n = 764). Reports of SCD and iADL difficulties were extracted from neuropsychological reports and coded by two independent raters. We also examined responses on self- and family-rated questionnaires of executive functioning and iADL difficulties.

Anglosphere and International patients did not differ on overall, memory, or attention SCD, or overall iADL difficulties based on interviews. Anglosphere patients reported more executive and language SCD during the interview but International care-partners reported more current executive dysfunction on a questionnaire. International patients and care-partners reported more iADL difficulties on a questionnaire, which they ascribed to motor (not cognitive) symptoms. The effects on questionnaires were small and persisted after accounting for depression severity ratings.

There were no consistent group differences in the number or pervasiveness of SCD or iADL difficulties reported by Anglosphere versus International groups. Immigration status has limited effect on these subjective elements and they should be given significant weight when diagnosing cognitive dysfunction in PD.

The INECO Frontal Screening (IFS) and the Frontal Assessment Battery (FAB) are executive dysfunction (ED) screening tools that can distinguish patients with neurodegenerative disorders from healthy controls and, to some extent, between dementia subtypes. This paper aims to examine the suitability of these tests in assessing early-onset cognitive impairment and dementia patients.

In a memory clinic patient cohort (age mean = 57.4 years) with symptom onset at ≤65 years, we analyzed the IFS and the FAB results of four groups: early-onset dementia (EOD, n = 49), mild cognitive impairment due to neurological causes (MCI-n, n = 34), MCI due to other causes such as depression (MCI-o, n = 99) and subjective cognitive decline (SCD, n = 14). Data were gathered at baseline and at 6 and 12 months. We also studied the tests’ accuracy in distinguishing EOD from SCD patients and ED patients from those with intact executive functioning. Correlations with neuropsychological measures were also studied.

The EOD group had significantly (p < .05) lower IFS and FAB total scores than the MCI-o and SCD groups. Compared with the FAB, the IFS showed more statistically significant (p < .05) differences between diagnostic groups, greater accuracy (IFS AUC = .80, FAB AUC = .75, p = .036) in detecting ED and marginally stronger correlations with neuropsychological measures. We found no statistically significant differences in the EOD group scores from baseline up to 6- or 12-months follow-up.

While both tests can detect EOD among memory clinic patients, the IFS may be more reliable in detecting ED than the FAB.

Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another.

Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort.

Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011).

Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.

Few studies have evaluated in-home teleneuropsychological (teleNP) assessment and none, to our knowledge, has evaluated the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study evaluates the reliability of the in-home UDS v3.0 t-cog with a prior in-person UDS v3.0 evaluation.

One hundred and eighty-one cognitively unimpaired or cognitively impaired participants from a longitudinal study of memory and aging completed an in-person UDS v3.0 and a subsequent UDS v3.0 t-cog evaluation (∼16 months apart) administered either via video conference (n = 122) or telephone (n = 59).

We calculated intraclass correlation coefficients (ICCs) between each time point for the entire sample. ICCs ranged widely (0.01–0.79) but were generally indicative of “moderate” (i.e., ICCs ranging from 0.5–0.75) to “good” (i.e., ICCs ranging from 0.75–0.90) agreement. Comparable ICCs were evident when looking only at those with stable diagnoses. However, relatively stronger ICCs (Range: 0.35–0.87) were found between similarly timed in-person UDS v3.0 evaluations.

Our findings suggest that most tests on the UDS v3.0 t-cog battery may serve as a viable alternative to its in-person counterpart, though reliability may be attenuated relative to the traditional in-person format. More tightly controlled studies are needed to better establish the reliability of these measures.

People with neurodegenerative disease and mild cognitive impairment (MCI) may have an elevated risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may be disproportionally affected by coronavirus disease 2019 (COVID-19) once infected.

To review all eligible studies and quantify the strength of associations between various pre-existing neurodegenerative disorders and both SARS-CoV-2 susceptibility and COVID-19 illness course and outcome.

Pre-registered systematic review with frequentist and Bayesian meta-analyses. Systematic searches were executed in PubMed, Web of Science and preprint servers. The final search date was 9 January 2023. Odds ratios (ORs) were used as measures of effect.

In total, 136 primary studies (total sample size n = 97 643 494), reporting on 268 effect-size estimates, met the inclusion criteria. The odds for a positive SARS-CoV-2 test result were increased for people with pre-existing dementia (OR = 1.83, 95% CI 1.16–2.87), Alzheimer's disease (OR = 2.86, 95% CI 1.44–5.66) and Parkinson's disease (OR = 1.65, 95% CI 1.34–2.04). People with pre-existing dementia were more likely to experience a relatively severe COVID-19 course, once infected (OR = 1.43, 95% CI 1.00–2.03). People with pre-existing dementia or Alzheimer's disease were at increased risk for COVID-19-related hospital admission (pooled OR range: 1.60–3.72). Intensive care unit admission rates were relatively low for people with dementia (OR = 0.54, 95% CI 0.40–0.74). All neurodegenerative disorders, including MCI, were at higher risk for COVID-19-related mortality (pooled OR range: 1.56–2.27).

Our findings confirm that, in general, people with neurodegenerative disease and MCI are at a disproportionally high risk of contracting COVID-19 and have a poor outcome once infected.

Neuropsychiatric symptoms are common in subjects with MCI and associated with higher risk of progression to AD. The cognitive and neuroanatomical correlates of neuropsychiatric symptoms in MCI have not been fully elucidated. In this study, we sought to evaluate the association between neuropsychiatric symptoms, cognitive function, regional tau deposition, and brain volumes in MCI subjects.

A total of 233 MCI and 305 healthy comparisons were selected from the ADNI-3 cohort. All the subjects underwent a comprehensive neuropsychological assessment, volumetric MR brain scan, and Flortaucipir PET for in vivo assessment of regional tau deposition. Prevalence of neuropsychiatric symptoms was evaluated by means of the NPI questionnaire. Multivariate analyses of variance were used to detect differences in cognitive and imaging markers in MCI subjects with and without neuropsychiatric symptoms.

61.4% MCI subjects showed at least one neuropsychiatric symptom, with the most prevalent ones being depression (26.1%), irritability (23.6%), and sleep disturbances (23.6%). There was a significant effect of neuropsychiatric symptoms on cognitive tests of frontal and executive functions. MCI subjects with neuropsychiatric symptoms showed reduced brain volumes in the orbitofrontal and posterior cingulate cortices, while no effects were detected on regional tau deposition. Posterior cingulate cortex volume was the only predictor of global neuropsychiatric burden in this MCI population.

Neuropsychiatric symptoms occur early in the AD trajectory and are mainly related to defects of control executive abilities and to the reduction of gray matter volume in the orbitofrontal and posterior cingulate cortices. A better understanding of the cognitive and neuroanatomical mechanisms of neuropsychiatric symptoms in MCI could help develop more targeted and efficacious treatment alternatives.

Apathy is a common symptom in mild cognitive impairment (MCI) and may predict progression to dementia. Little research, however, has investigated the longitudinal trajectory of apathy in patients with MCI or controlled for depression, which can mimic apathy, when examining its clinical correlates. The current study sought to address these issues.

A prospective longitudinal study was conducted over 3 years.

Nine memory clinics around Australia

One hundred and eighty-five patients with MCI at baseline.

Measures of cognition, function, neuropsychiatric symptoms, caregiver burden, and medication use were completed annually with additional assessments at 3 and 6 months. Patients were also assessed for dementia by expert clinicians at these time points.

Of 164 patients who completed measures of neuropsychiatric symptoms, 59 (36.0%) had apathy and 61 (37.2%) had depression. The proportion affected by apathy and overall apathy scores increased over time, in contrast to measures of depression, which remained relatively stable. Apathy was associated with incident dementia and worse cognition, function, neuropsychiatric symptoms, and caregiver burden independent of both depression and incident dementia. Depression was associated with worse function, albeit to lesser degree than apathy, and neuropsychiatric symptoms.

Apathy increases in MCI and is associated with worse clinical outcomes. These findings provide further evidence for apathy as a marker of clinical decline in older people and poorer outcomes across neurocognitive disorders.

1. (1) Recently, studies have shown that CBT for older people living with dementia has been effective in treating their depression and anxiety. However, evidence for the efficacy of CBT and other curative or care options for people living with dementia is limited in Japan.

2. (2) We studied a short-period CBT program and found that it was likely to be feasible and acceptable for use among older Japanese people with mild cognitive impairment, that it may improve negative mood among this group, and that it may lessen the care burden for caregivers.

3. (3) Furthermore, we found that caregiver involvement in the implementation of CBT for older people may be effective in improving the mood of family members.

Social functioning is crucial for daily living and is an essential indicator of dementia in patients with Parkinson's disease. The pattern of social functioning in patients with Parkinson's disease without dementia (i.e. those who are cognitively intact or have mild cognitive impairment (PD-MCI)) and its determinants are unclear.

In exploring the heterogeneity of social functioning among patients with Parkinson's disease-associated dementia, we determined the optimal cut-off score of the Parkinson's Disease Social Functioning Scale (PDSFS) for patients with PD-MCI, and the variables influencing patients’ social functioning.

A total of 302 participants underwent the Mini-Mental State Examination (MMSE) and PDSFS; 120 patients with Parkinson's disease completed the measurements (MMSE, Activities of Daily Living Scale and Neuropsychiatric Inventory). Group comparisons, receiver operating characteristic curves, Spearman correlation and multiple and hierarchical regression analyses were conducted.

The PD-MCI group scored the lowest on the PDSFS (F = 10.10, P < 0.001). The PDSFS cut-off score was 53 (area under the curve 0.700, sensitivity 0.800, specificity 0.534). The MMSE (β = 0.293, P = 0.002), Activities of Daily Living Scale (β = 0.189, P = 0.028) and Neuropsychiatric Inventory (β = −0.216, P = 0.005) scores predicted the PDSFS score. Further, there was an interaction effect between the Activities of Daily Living Scale and Neuropsychiatric Inventory scores on the PDSFS score (β = 0.305, P < 0.001).

We determined a PDSFS cut-off score for detecting PD-MCI and found that patients with PD-MCI have social dysfunction. Future research should focus on the effects of neuropsychiatry symptoms and activities of daily living on social functioning, and tailor the intervention programme for patients with Parkinson's disease.

Prevalence of cognitive decline and dementia is rising globally, with more than 10 million new cases every year. These conditions cause a significant burden for individuals, their caregivers, and health care systems. As no causal treatment for dementia exists, prevention of cognitive decline is of utmost importance. Notably, alcohol is among the most significant modifiable risk factors for cognitive decline.

Longitudinal data across 15 years on 6,967 individuals of the Survey of Health, Ageing and Retirement in Europe were used to analyze the effect of alcohol consumption and further modifiable (i.e., smoking, depression, and educational obtainment) and non-modifiable risk factors (sex and age) on cognitive functioning (i.e., memory and verbal fluency). For this, a generalized estimating equation linear model was estimated for every cognitive test domain assessed.

Consistent results were revealed in all three regression models: A nonlinear association between alcohol consumption and cognitive decline was found—moderate alcohol intake was associated with overall better global cognitive function than low or elevated alcohol consumption or complete abstinence. Furthermore, female sex and higher educational obtainment were associated with better cognitive function, whereas higher age and depression were associated with a decline in cognitive functioning. No significant association was found for smoking.

Our data indicate that alcohol use is a relevant risk factor for cognitive decline in older adults. Furthermore, evidence-based therapeutic concepts to reduce alcohol consumption exist and should be of primary interest in prevention measures considering the aging European population.

Previous research has indicated that cognition and executive function are associated with decision-making, however the impact of mild cognitive impairment (MCI) on decision-making under explicit risk conditions is unclear. This cross-sectional study examined the impact of MCI, and MCI subtypes, on decision-making on the Game of Dice Task (GDT), among a cohort of older adults.

Data from 245 older adult participants (aged 72–78 years) from the fourth assessment of the Personality and Total Health Through Life study were analyzed. A diagnostic algorithm identified 103 participants with MCI, with subtypes of single-domain amnestic MCI (aMCI-single; n = 38), multi-domain amnestic MCI (aMCI-multi; n = 31), and non-amnestic MCI (n = 33), who were compared with an age-, sex-, education-, and income-matched sample of 142 cognitively unimpaired older adults. Decision-making scores on the GDT (net score, single number choices, and strategy changes) were compared between groups using nonparametric tests.

Participants with MCI showed impaired performance on the GDT, with higher frequencies of single number choices and strategy changes. Analyses comparing MCI subtypes indicated that the aMCI-multi subtype showed increased frequency of single number choices compared to cognitively unimpaired participants. Across the sample of participants, decision-making scores were associated with measures of executive function (cognitive flexibility and set shifting).

MCI is associated with impaired decision-making performance under explicit risk conditions. Participants with impairments in multiple domains of cognition showed the clearest impairments. The GDT may have utility in discriminating between MCI subtypes.

Cognitive impairment is common post-stroke. There is a need to understand patterns of early cognitive recovery post-stroke to guide both clinical and research practice. The aim of the study was to map the trajectory of cognitive recovery during the first week to 90-days post-stroke using serial computerised assessment.

An observational cohort study recruited consecutive stroke patients admitted to a stroke unit within 48 hours of onset. Cognitive function was assessed using the computerised Cambridge Neuropsychological Test Automated Battery (CANTAB) daily for seven days, then 14, 30 and 90 days post-stroke. The CANTAB measured visual episodic memory and learning, information processing speed, visuo-spatial working memory, complex sustained attention and mental flexibility. Repeated measures MANOVA/ANOVA with Least Squares Difference post-hoc analyses were performed to ascertain significant change over time.

Forty-eight participants, mean age 73, primarily mild, ischaemic stroke, completed all assessment timepoints. There was a trajectory of early, global cognitive improvement, indicative of a post-stroke delirium, that largely stabilised between 6 and 14-days post-stroke. Change over time was examined within each cognitive test, with one measure stabilising by day 6 (Reaction Time) and others detecting improving performances up to 14 days post-stroke.

Serial, computerised cognitive assessment can effectively map post-stroke cognitive recovery and revealed an early phase of global improvement over 14 days that is evidence for an acute post-stroke delirium. Resolution of post-stroke delirium in the second week following mild stroke indicates more extensive neuropsychological testing may be undertaken earlier than previously thought.

Several studies showed that transcranial direct current stimulation (tDCS) enhances cognition in patients with mild cognitive impairment (MCI), however, whether tDCS leads to additional gains when combined with cognitive training remains unclear. This study aims to compare the effects of a concurrent tDCS-cognitive training intervention with either tDCS or cognitive training alone on a group of patients with MCI.

The study was a 3-parallel-arm study. The intervention consisted of 20 daily sessions of 20 minutes each. Patients (n = 62) received anodal tDCS to the left dorsolateral prefrontal cortex, cognitive training on 5 cognitive domains (orientation, attention, memory, language, and executive functions), or both. To examine intervention gains, we examined global cognitive functioning, verbal short-term memory, visuospatial memory, and verbal fluency pre- and post-intervention.

All outcome measures improved after the intervention in the 3 groups. The improvement in global cognitive functioning and verbal fluency was significantly larger in patients who received the combined intervention. Instead, the intervention gain in verbal short-term memory and visuospatial memory was similar across the 3 groups.

tDCS, regardless of the practicalities, could be an efficacious treatment in combination with cognitive training given the increased effectiveness of the combined treatment.

Future studies will need to consider individual differences at baseline, including genetic factors and anatomical differences that impact the electric field generated by tDCS and should also consider the feasibility of at-home treatments consisting of the application of tDCS with cognitive training.

Cognitive impairment is one of the most common symptoms of anti-leucine rich glioma inactivated 1 (anti-LGI-1) encephalitis, but little is known about the cognitive profile of these patients. This study characterized the cognitive profile of patients with anti-LGI-1 encephalitis and compared patterns of impairment to healthy controls and other patient groups with known temporal lobe/limbic involvement.

A retrospective analysis of adult patients with anti-LGI-1 encephalitis who underwent neuropsychological assessment was conducted. Performance patterns of anti-LGI-1 patients were compared to patients deemed cognitively healthy (HC), as well as patients with amnestic mild cognitive impairment (aMCI) and temporal lobe epilepsy (TLE).

Among 10 anti-LGI encephalitis patients (60% male, median age 67.5 years) who underwent neuropsychological testing (median = 38.5 months from symptom onset), cognitive deficits were common, with 100% of patients showing impairment (≤1.5 SD below mean) on 1+ measures and 80% on 2+ measures. Patients with anti-LGI-1 encephalitis performed worse than controls on measures of basic attention, vigilance, psychomotor speed, complex figure copy, and aspects of learning/memory. Of measures which differed from controls, there were no differences between the anti-LGI-1 and TLE patients, while the anti-LGI-1 patients exhibited higher rates of impairment in basic attention and lower rates of delayed verbal memory impairment compared to the aMCI patients.

Long-term cognitive deficits are common in patients with anti-LGI-1 encephalitis and involve multiple domains. Future research in larger samples is needed to confirm these findings.