We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer’s disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment.

Systematic review, Meta-Analysis

We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023.

RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included.

Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423).

The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer’s Disease Assessment Scale–Cognitive Subscale (SMD = −0.96 [−1.32, −0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity.

The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.

Valid estimates of premorbid cognitive functioning (PMIQ) are crucial for the assessment of older adults at risk for Alzheimer’s disease. We investigated the relationship between the NIH Toolbox-Cognition Battery’s (NIHTB-CB) Oral Reading Recognition (ORR) subtest and Wechsler Test of Adult Reading scores (WTAR, convergent validity). We also compared ORR to NIHTB-CB Flanker scores, where null relationships were expected (discriminant validity).

The WTAR and NIHTB-CB were administered to 130 cognitively normal (CN) and 113 participants with mild cognitive impairment (MCI). Participants were community-dwelling, older Black and White adults, ages 55–88 years. Data analysis used uncorrected standard scores and Bayesian bivariate correlations. Supplemental materials include intraclass correlations.

ORR and WTAR scores were strongly positively associated, while ORR and Flanker scores were unrelated. This pattern held when restricting analyses to the two cognitive status groups, the two racial groups, and the four race-by-diagnosis subgroups.

The findings demonstrate convergent and discriminant validity and support NIHTB-CB ORR scores as valid estimates of scores on a PMIQ measure in older Black and White adults with and without MCI.

Olfactory dysfunction and depression are common in later life, and both have been presented as risk factors for dementia. Our purpose was to investigate the associations between these two risk factors and determine if they had an additive effect on dementia risk.

Olfactory function was assessed using the Brief Smell Identification Test (BSIT), and depression was classified using a combination of the 15-item Geriatric Depression Scale (GDS) score and current antidepressant use. Cross-sectional associations between depression and olfactory function were examined using correlations. Cox regression analyses were conducted to examine the longitudinal relationship between olfaction and depression and incident dementia across 12-years of follow-up.

Participants were 780 older adults (aged 70–90 years; 56.5% female) from the Sydney Memory and Ageing Study (MAS) without a diagnosis of dementia at baseline.

Partial correlation revealed a nonsignificant association between baseline depression and olfactory function after accounting for covariates (r = −.051, p = .173). Cox regression showed that depression at baseline (hazard ratio = 1.706, 95% CI 1.185–2.456, p = .004) and lower BSIT scores (HR = .845, 95%CI .789–.905, p < .001) were independently associated with a higher risk of incident dementia across 12 years. Entering both predictors together improved the overall predictive power of the model.

Lower olfactory identification scores and depressive symptoms predict incident dementia over 12 years. The use of BSIT scores and depression in conjunction provides a greater ability to predict dementia than either used alone. Assessment of olfactory function and depression screening may provide clinical utility in the early detection of dementia.

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).

Mild cognitive impairment (MCI) represent a state of cognitive function between normal aging and dementia and does not always progress to dementia. Neuroinflammation has a key role in the pathogenesis of neurodegeneration. Determining the associations of neuroinflammatory markers in the blood with clinical disease severity may be useful for early diagnosis of cognitive impairment and prediction of the development of severe dementia.

The aim of our study was to compare the serum concentration of a panel of inflammatory markers in patients with MCI and dementia as well as their associations with clinical symptoms.

Patients were evaluated using Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Montreal Cognitive Assessment scales (MoCA), Clinical Dementia rating (CDR) and Hospital Anxiety Depression Scale (HADS). We determined the serum concentration of a panel of inflammatory markers (25 units) cytokines, chemokines, growth factors and several others on Mulliplex and prepared multivariate analysis to investigate associations between clinical features and serum concentration.

Patients with dementia had lower scores on scales than the control and MCI groups. MCI patients were equal to the control group, except for the MMSE scale. EGF, eotaxin-1, GRO-α, IP-10, IL-8, MIP-1β, sCD40L, TNF-α, MDC and MCP-1, VEGF were differ between groups. Multivariate analysis identified some neuroinflammatory parameters associated with the severity of the disease.

We identified some neuroinflammatory parameters associated with dementia and MCI. Many of them have been poor described and data is contradictory. It is necessary to investigate these parameters as potential biomarkers of neurodegeneration in further studies.

No significant relationships.

Cognitive impairments have a considerable impact on the functioning of patients, their socialization and level of disability. Cognitive deficits significantly deteriorate the quality of patients’ life. Currently, the possibilities of pharmacological correction of cognitive disorders in patients with epilepsy are limited.

Study of non-pharmacological program of cognitive disorder correction in patients with epilepsy and the assessment of its efficiency.

We have studied the features of clinical and psychopathological manifestations in patients suffering from epilepsy. The study included 146 patients with epilepsy (85 men and 61 women) who were receiving inpatient care. The following psychodiagnostic techniques were used: MOCA test, Mini Mult test, Münsterberg test, depression and Hamilton anxiety scale, quality of life scale. 63 patients received cognitive training online, of which 30 patients also used psychoeducation methods.

According to the MoCA findings, patients with epilepsy showed cognitive decline, the average score was 20.72, whereas healthy persons’ average score was 27.36. The Quality of Life Scale: the average rate among all examined persons was 69.45 out of 100, 78.60 were the results of healthy persons. In patients with PG1, who used cognitive training and psychoeducation the results of the MoCA test showed an improvement in cognitive functions (1.4, p <0.001) and increased subjective assessment of quality of life (2.77, p <0.05).

The study of the use of cognitive training and psychoeducation in patients with epilepsy for cognitive functions, quality of life resulted in a positive outcome. Cognitive online training is an encouraging area in the rehabilitation of patients with cognitive decline.

No significant relationships.

Impaired olfaction may be a biomarker for early Lewy body disease, but its value in mild cognitive impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer’s disease (MCI-AD) and healthy older adults. We hypothesized that olfactory function would be worse in probable MCI-LB than in both MCI-AD and healthy comparison subjects (HC).

Cross-sectional study assessing olfaction using Sniffin’ Sticks 16 (SS-16) in MCI-LB, MCI-AD, and HC with longitudinal follow-up. Differences were adjusted for age, and receiver operating characteristic (ROC) curves were used for discriminating MCI-LB from MCI-AD and HC.

Participants were recruited from Memory Services in the North East of England.

Thirty-eight probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB, and 32HC.

Olfaction was assessed using SS-16 and a questionnaire.

Participants with probable MCI-LB had worse olfaction than both MCI-AD (age-adjusted mean difference (B) = 2.05, 95% CI: 0.62–3.49, p = 0.005) and HC (B = 3.96, 95% CI: 2.51–5.40, p < 0.001). The previously identified cutoff score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69–94%), but 30% specificity versus MCI-AD. ROC analysis found a lower cutoff of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vs HC). Asking about olfactory impairments was not useful in identifying them.

MCI-LB had worse olfaction than MCI-AD and normal aging. A lower cutoff score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services.

Social cognition is impaired in mild cognitive impairment (MCI) and dementia. However, its relationship to social functioning and perceived social support has yet to be explored. Here, we examine how theory of mind (ToM) relates to social functioning in MCI and dementia.

Older adults (cognitively normal = 1272; MCI = 132; dementia = 23) from the PATH Through Life project, a longitudinal, population-based study, were assessed on the Reading the Mind in the Eyes Test (RMET), measures of social functioning, and social well-being. The associations between RMET performance, social functioning, and cognitive status were analysed using generalised linear models, adjusting for demographic variables.

Participants with MCI (b=−.52, 95% CI [−.70, −.33]) and dementia (b=−.78, 95% CI [−1.22, −.34]) showed poorer RMET performance than cognitively normal participants. Participants with MCI and dementia reported reduced social network size (b=−.21, 95% CI [−.40, −.02] and b=−.90, 95% CI [−1.38, −.42], respectively) and participants with dementia reported increased loneliness (b = .36, 95% CI [.06, .67]). In dementia, poorer RMET performance was associated with increased loneliness (b=−.07, 95% CI [−.14, −.00]) and a trend for negative interactions with partners (b=−.37, 95% CI [−.74, .00]), but no significant associations were found in MCI.

MCI and dementia were associated with poor self-reported social function. ToM deficits were related to poor social function in dementia but not MCI. Findings highlight the importance of interventions to address social cognitive deficits in persons with dementia and education of support networks to facilitate positive interactions and social well-being.

The Verbal Naming Test (VNT) is an auditory-based measure of naming or word finding. The current multisite study sought to evaluate the reliability and validity of the VNT in the detection of major and mild neurocognitive disorder (NCD).

This study analyzed clinical data from two outpatient neuropsychology clinics (N = 188 and N = 77) and a geriatric primary care clinic (N = 104). Cronbach’s alpha and Spearman correlations with other measures were calculated. ROC analyses were used to calculate sensitivity, specificity, positive predictive power, and negative predictive power for the detection of major and mild NCD per DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) criteria.

The VNT was found to have strong reliability (Cronbach’s alpha = .90) and high convergent validity with a commonly used picture-naming task (NAB Naming, Spearman’s rho = .65, p < .001). The VNT showed good sensitivity and specificity for the detection of NCDs, particularly major NCD, with an area under the curve of .85, sensitivity of .80, and specificity of .75. A possible discontinue rule is also suggested for clinicians to use.

These findings provide compelling evidence for the use of the VNT to detect neurocognitive impairment in a clinical setting. The VNT provides a reliable alternative to picture-naming tasks, which may be advantageous when working with visually impaired patients or conducting evaluations over telehealth.

Recently published diagnostic criteria for mild cognitive impairment with Lewy bodies (MCI-LB) include five neuropsychiatric supportive features (non-visual hallucinations, systematised delusions, apathy, anxiety and depression). We have previously demonstrated that the presence of two or more of these symptoms differentiates MCI-LB from MCI due to Alzheimer's disease (MCI-AD) with a likelihood ratio >4. The aim of this study was to replicate the findings in an independent cohort.

Participants ⩾60 years old with MCI were recruited. Each participant had a detailed clinical, cognitive and imaging assessment including FP-CIT SPECT and cardiac MIBG. The presence of neuropsychiatric supportive symptoms was determined using the Neuropsychiatric Inventory (NPI). Participants were classified as MCI-AD, possible MCI-LB and probable MCI-LB based on current diagnostic criteria. Participants with possible MCI-LB were excluded from further analysis.

Probable MCI-LB (n = 28) had higher NPI total and distress scores than MCI-AD (n = 30). In total, 59% of MCI-LB had two or more neuropsychiatric supportive symptoms compared with 9% of MCI-AD (likelihood ratio 6.5, p < 0.001). MCI-LB participants also had a significantly greater delayed recall and a lower Trails A:Trails B ratio than MCI-AD.

MCI-LB is associated with significantly greater neuropsychiatric symptoms than MCI-AD. The presence of two or more neuropsychiatric supportive symptoms as defined by MCI-LB diagnostic criteria is highly specific and moderately sensitive for a diagnosis of MCI-LB. The cognitive profile of MCI-LB differs from MCI-AD, with greater executive and lesser memory impairment, but these differences are not sufficient to differentiate MCI-LB from MCI-AD.

The present study investigated the ability of the Multilingual Naming Test (MINT), a picture naming test recently added to the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set neuropsychological test battery, to detect naming impairment (i.e., dysnomia) across stages of Alzheimer’s disease (AD).

Data from the initial administration of the MINT were obtained on NACC participants who were cognitively normal (N = 3,981) or diagnosed with mild cognitive impairment (N = 852) or dementia (N = 1,148) with presumed etiology of AD. Dementia severity was rated using the Clinical Dementia Rating (CDR) scale.

Cross-sectional multiple regression analyses revealed significant effects of diagnostic group, sex, education, age, and race on naming scores. Planned comparisons collapsing across age and education groups revealed significant group differences in naming scores across levels of dementia severity. ROC curve analyses showed good diagnostic accuracy of MINT scores for distinguishing cognitively normal controls from AD dementia, but not from MCI. Within the cognitively normal group, there was a robust interaction between age and education such that naming scores exhibited the most precipitous drop across age groups for the least educated participants. Additionally, education effects were stronger in African-Americans than in Whites (a race-by-education interaction), and race effects were stronger in older than in younger age groups (a race-by-age interaction).

The MINT successfully detects naming deficits at different levels of cognitive impairment in patients with MCI or AD dementia, but comparison to age, sex, race, and education-corrected norms to determine impairment is essential.

The proliferation of unmanned aerial vehicle (UAV) technology has the potential to change the way medical incident commanders (ICs) respond to mass-casualty incidents (MCIs) in triaging victims. The aim of this study was to compare UAV technology to standard practice (SP) in triaging casualties at an MCI.

A randomized comparison study was conducted with 40 paramedic students from the Holland College Paramedicine Program (Charlottetown, Prince Edward Island, Canada). Using a simulated motor vehicle collision (MVC) with moulaged casualties, iterations of 20 students were used for both a day and a night trial. Students were randomized to a UAV or a SP group. After a brief narrative, participants either entered the study environment or used UAV technology where total time to triage completion, GREEN casualty evacuation, time on scene, triage order, and accuracy were recorded.

A statistical difference in the time to completion of 3.63 minutes (95% CI, 2.45 min-4.85 min; P=.002) during the day iteration and a difference of 3.49 minutes (95% CI, 2.08 min-6.06 min; P=.002) for the night trial with UAV groups was noted. There was no difference found in time to GREEN casualty evacuation, time on scene, or triage order. One-hundred-percent accuracy was noted between both groups.

This study demonstrated the feasibility of using a UAV at an MCI. A non-clinical significant difference was noted in total time to completion between both groups. There was no increase in time on scene by using the UAV while demonstrating the feasibility of remotely triaging GREEN casualties prior to first responder arrival.

Jain T, Sibley A, Stryhn H, Hubloue I.Comparison of unmanned aerial vehicle technologyassisted triage versus standard practice in triaging casualties by paramedic students in a mass-casualty incident scenario. Prehosp Disaster Med. 2018;33(4):375–380

Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.

We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.

The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).

Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.

Despite recent interest in community-based screening programs to detect undiagnosed cognitive disorder, little is known about whether screening leads to further diagnostic evaluation, or the effects of such programs in terms of actual changes in patient or caregiver behavior. This study followed up informants of older adults (i.e. caregivers of patients who completed informant-based screening regarding the patient) following participation in a study screening for undiagnosed memory problems, to explore uptake of further diagnostic evaluation or treatment, advance planning or preparations, lifestyle changes, medication adherence, and use of support services.

A total of 140 informants of older adult patients were surveyed four to fifteen months following participation in a cognitive screening study. The informants were interviewed with a study-specific survey about cognitive assessment, advance planning, lifestyle changes, and use of support services and general medication adherence.

A minority of patients and informants had engaged in advance planning or made relevant lifestyle changes following cognitive screening. Those assessed as being at higher risk of memory problems were more likely to have attended a full diagnostic evaluation, engaged in support services and experienced medication adherence difficulties.

Only a small proportion of patients participating in cognitive screening subsequently engaged in diagnostic evaluation, advance planning, or lifestyle changes. However, those with higher risk of cognitive impairment were generally more likely to take some action following cognitive screening. Those at higher risk were also more vulnerable due to greater difficulties with medication adherence.

Memory deficits are dominant in dementia and are positively correlated with electroencephalographic (EEG) beta power. EEG beta power can predict the progression of Alzheimer´s (AD) as early as at the stage of mild cognitive impairment (MCI) and could possibly be used as surrogate marker for memory impairment. The objective of this study is to analyze the relationship between frontal and parietal EEG beta power and memory-test outcome. Frontal and parietal beta power is analyzed for a resting state and an eyes-closed backward counting condition and related to memory impairment parameters.

A total of 28 right-handed female geriatric patients (mean age = 80.6) participated voluntarily in this study. Beta 1 (12.9–19.2 Hz) and beta 2 (19.2–32.4 Hz) EEG power at F3, F4, Fz, P3, P4, and Pz are correlated with immediate wordlist recall, delayed wordlist recall, recognition of learned words, and delayed figure recall. For classification between impaired and intact memory, we calculated a binary logistic regression model with memory impairment as a dependent variable and beta 2 power as an independent variable.

We found significant positive correlations between frontal and parietal beta power and delayed memory recall. A significant correlation (Bonferroni correction, p < 0.05) was found at F4 beta 2 during backward counting. The binary logistic regression model with F4 beta 2 power during the counting condition as a predictor yielded a sensitivity of 76.9% (95% CI) and a specificity of 73.3% (95% CI) for classifying patients into “verbal-memory impaired” and “intact.”

EEG beta 2 power recorded during a backward counting condition with eyes closed can be used as surrogate marker for verbal memory impairment in geriatric patients. Antidepressant treatment was correlated with EEG data in resting state but not in counting condition. Further studies are necessary to verify the results of this pilot study.

The Mini-Addenbrooke's Cognitive Examination (MACE) is a new brief cognitive screening instrument for dementia and mild cognitive impairment (MCI). Historical data suggest that MACE may be comparable to the Montreal Cognitive Assessment (MoCA), a well-established cognitive screening instrument, in secondary care settings, but no head-to-head study has been reported hitherto.

A pragmatic diagnostic accuracy study of MACE and MoCA was undertaken in consecutive patients referred over the course of one year to a neurology-led Cognitive Function Clinic, comparing their performance for the diagnosis of dementia and MCI using various test metrics.

In a cohort of 260 patients with dementia and MCI prevalence of 17% and 29%, respectively, both MACE and MoCA were quick and easy to use and acceptable to patients. Both tests had high sensitivity (>0.9) and large effect sizes (Cohen's d) for diagnosis of both dementia and MCI but low specificity and positive predictive values. Area under the receiver operating characteristic curve was excellent for dementia diagnosis (both >0.9) but less good for MCI (MoCA good and MACE fair). In contrast, weighted comparison suggested test equivalence for dementia diagnosis but with a slight net benefit for MACE for MCI diagnosis.

MACE is an acceptable and accurate test for the assessment of cognitive problems, with performance comparable to MoCA. MACE appears to be a viable alternative to MoCA for testing patients with cognitive complaints in a secondary care setting.