Memory Clinic Research Articles

Insomnia symptoms among caregivers of persons with cognitive decline in an outpatient memory clinic

BackgroundSignificant insomnia symptoms can have important impacts on the health and quality of life of caregivers of persons with cognitive decline (PwCD). ObjectiveTo characterize the prevalence of clinically significant insomnia symptoms using the recommended community cutoff for the Insomnia Severity Index (ISI; ≥10) and identify correlates of the presence of symptoms. MethodsEighty PwCD caregivers were recruited from a memory and aging care clinic in an academic medical center and completed all study procedures (Mage = 66.05 ± 13.45 years; 93.75 % non-Hispanic White, 71.00 % spouses, 81.25 % co-dwelling with PwCD). Caregivers completed the ISI, Hospital Anxiety and Depression Scale, and Zarit Burden Interview (12-item). ResultsOne-third of PwCD caregivers reported clinically significant insomnia symptoms. Caregivers reporting these symptoms were more likely to report difficulty sleeping due to stressful/anxious thoughts about the PwCD compared to caregivers without insomnia symptoms (p < .001). No group differences were detected between caregivers with and without insomnia symptoms based on reported frequency of PwCD nighttime care needs or behaviors. Caregivers with insomnia symptoms endorsed significantly higher depression symptoms, anxiety symptoms, and caregiving psychological burden (ps < 0.001). ConclusionsPwCD stress and psychological burden, but not PwCD nighttime factors, appear to be associated with clinically significant insomnia symptoms among PwCD caregivers. Existing evidenced-based treatments for insomnia, such as cognitive behavioral therapy for insomnia, may be effective in this cohort.

Effects of a nurse-led staged integral art-based cognitive intervention for older adults on the Alzheimer's disease spectrum: A randomized controlled trial

BackgroundCombined art activities can improve the neural network function within various brain regions involved in emotions, cognition, and behavior, thereby preventing or reversing cognitive decline. However, few studies have systematically examined its effects. Furthermore, the impact of nurse-led art-based cognitive intervention on cognitive and psychological health is unclear. ObjectiveTo evaluate the effects of a nurse-led staged integral art-based cognitive intervention in older adults on the Alzheimer's disease spectrum. DesignThis was a randomized wait-list controlled trial with allocation concealment and blinding of outcome assessors and data analysts. All data were collected between April 2021 and January 2023 and analyzed from January to March 2023. SettingOne memory clinic and four medical partnership communities. ParticipantsA total of 144 participants with subjective or objective memory decline (aged ≥60 years). MethodsParticipants were randomized into an intervention group (n = 72) and a wait-list control group (n = 72), in a 1:1 ratio. The intervention group underwent a 16-week, 24-session nurse-led staged integral art-based cognitive intervention program, which was based on neurocognitive function training patterns. The control group underwent the program after the follow-up assessment. General and specific domains of cognitive function and other health-related outcomes were measured at baseline (T0), immediately after the intervention (T1), and at the 6-month follow-up (T2). ResultsOf the 144 participants (mean [SD] age, 71.6 [5.8] years; 50 [34.7 %] males and 94 [65.3 %] females), 130 and 115 completed the questionnaires at T1 and T2, respectively. The average attendance rate in the intervention group was 86.0 %. At T1, the intervention group showed greater improvement than the control group did in general cognitive functions (MoCA, between-group mean difference, 1.4 [95 % CIs, 0.4 to 2.5], p = 0.009). Additionally, the intervention group demonstrated statistically significant improvement compared to the control group in language, memory, quality of life, sleep quality and physical activity level at T1. Statistically significant group differences remained in sleep quality (PSQI, between-group mean difference, −1.3 [95 % CIs, −2.5 to −0.1], p = 0.035) at the 6-month follow-up. ConclusionsIn this randomized controlled trial of a nurse-led staged integral art-based cognitive intervention program, older adults on the Alzheimer's disease spectrum who participated in the program experienced improved cognition and psychological health. RegistrationThis study was registered with ChiCTR.org (ChiCTR2100044959) on April 3, 2021. Tweetable abstractA nurse-led staged integral art-based intervention for older adults on the Alzheimer's disease spectrum experienced improved cognition and psychological health.

User Experience of a (Semi-) Automated Cognitive Phone-Based Assessment Within a Memory Clinic Population.

We examined the user experience in different modalities (face-to-face, semi-automated phone-based, and fully automated phone-based) of cognitive testing in people with subjective cognitive decline and mild cognitive impairment. A total of 67 participants from the memory clinic of the Maastricht University Medical Center+ participated in the study. The study consisted of cognitive tests in different modalities, namely, face-to-face, semi-automated phone-based guided by a researcher, and fully automated phone-based without the involvement of a researcher. After each assessment, a user experience questionnaire was administered, including questions about, for example, satisfaction, simplicity, and missing personal contact, on a seven-point Likert scale. Non-parametric tests were used to compare user experiences across different modalities. In all modalities, user experiences were rated above average. The face-to-face ratings were comparable to the ratings of the semi-automated phone-based assessment, except for the satisfaction and recommendation items, which were rated higher for the face-to-face assessment. The face-to-face assessment was preferred above the fully automated phone-based assessment on all items. In general, the semi- and fully automated phone-based assessments were comparable (simplicity, conceivability, quality of sound, visiting the hospital, and missing personal contact), while on all the other items, the semi-automated phone-based assessment was preferred. User experience was rated high within all modalities. Simplicity, conceivability, comfortability, and participation scores were comparable in the semi-automated phone-based and face-to-face assessment. Based on these findings and earlier research on validation of the semi-automated phone-based assessment, the semi-automated assessment could be useful for screening for clinical trials, and after more research, in clinical practice.

Persistent delirium is associated with cerebrospinal fluid markers of neuronal injury.

Delirium is associated with the risk of future long-term cognitive impairment, but the degree to which markers of neuronal injury may be distinct or shared with dementia has yet to be comprehensively described. We investigated CSF biomarkers of dementia, astrocytosis and neuronal damage in a clinical cohort with persistent delirium, comparing them with an outpatient memory clinic sample. Our aim was to determine if different patterns of biomarker changes could implicate specific mechanisms for delirium-related neuronal injury over and above that attributable to comorbid dementia. We recruited 35 participants from the Prince of Wales Hospital, Sydney, Australia. We included inpatients with delirium persisting for at least 5 days (n = 15, 10 with underlying dementia) and participants from outpatient memory clinics (n = 20, 17 with dementia). CSF assays were as follows: amyloid-β42, amyloid-β40, phosphorylated tau181, neurofilament light chain and glial fibrillary acidic protein. We used propensity score matching to estimate effect sizes for each standardized CSF biomarker separately for persistent delirium (irrespective of underlying dementia) and dementia (irrespective of superimposed delirium). Compared with individuals without delirium, persistent delirium was associated with elevated glial fibrillary acidic protein (normalized coefficient per transformed standard deviation, β = 0.85; 95% confidence interval: 0.03-1.68) and neurofilament light chain (β = 1.1; 95% confidence interval: 0.5-1.6), but not phosphorylated tau181. Compared with individuals without dementia, glial fibrillary acidic protein, neurofilament light chain and phosphorylated tau181 were all increased to expected levels in dementia cases, with the former two biomarkers at levels comparable to those seen in persistent delirium [glial fibrillary acidic protein (β = 1.54; 95% confidence interval: 1.05-2.0) and neurofilament light chain (β = 0.65; 95% confidence interval: 0.24-1.1)]. Persistent delirium was linked with changes in CSF biomarkers not necessarily attributable to dementia. These findings support the potential that delirium is associated with direct neuronal injury independent of dementia pathophysiology. Whether this neuronal injury involves astrocyte dysfunction or direct axonal damage are both possibilities. Future work examining acute brain injury in delirium is needed.

Investigating patient eligibility for anti-amyloid monoclonal antibody treatment of Alzheimer's disease: real-world data from an Austrian psychiatric memory clinic population.

Pharmacological treatment options for patients with dementia owing to Alzheimer's disease are limited to symptomatic therapy. Recently, the US Food and Drug Administration approved the monoclonal antibody lecanemab for the treatment of amyloid-positive patients with mild cognitive impairment (MCI) and early Alzheimer´s dementia. European approval is expected in 2024. Data on the applicability and eligibility for treatment with anti-amyloid monoclonal antibodies outside of a study population are lacking. This study examined eligibility criteria for lecanemab in a real-world memory clinic population between 1 January 2022 and 31 July 2023. We conducted a retrospective, single-centre study applying the clinical trial eligibility criteria for lecanemab to out-patients of a specialised psychiatric memory clinic. Eligibility for anti-amyloid treatment was assessed following the phase 3 inclusion and exclusion criteria and the published recommendations for lecanemab. The study population consisted of 587 out-patients. Two-thirds were diagnosed with Alzheimer's disease (probable or possible Alzheimer's disease dementia in 43.6% of cases, n = 256) or MCI (23%, n = 135), and 33.4% (n = 196) were diagnosed with dementia or neurocognitive disorder owing to another aetiology. Applying all lecanemab eligibility criteria, 11 (4.3%) patients with dementia and two (1.5%) patients with MCI would have been eligible for treatment with this compound, whereas 13 dementia (5.1%) and 14 (10.4%) MCI patients met clinical inclusion criteria, but had no available amyloid status. Even in a memory clinic with a good infrastructure and sufficient facilities for dementia diagnostics, most patients do not meet the eligibility criteria for treatment with lecanemab.

One year analysis of Prospective Memory Clinics Registry in Qatar: A Critical Tool for Dementia Research and Policy Planning.

The Global Dementia Observatory (GDO) is a monitoring and accountability tool for the Global Action Plan on Public Response to Dementia 2017-25. Evidence from dementia registries may be utilized to better address WHO efforts in member countries, as well as to improve clinical practice and public health policy. The goal of this study was to analyze one-year data from a prospective memory clinic registry. This study was a baseline analysis of prospective memory clinics registry data of Qatar from January 1, 2023, through December 31, 2023. This study investigated the demographic, clinical, and lifestyle characteristics of 464 participants who were enrolled in memory clinics. Mild neurocognitive disorders were the most prevalent diagnoses in both sexes, affecting 61.5% of male patients and 63.7% of female patients. Dementia was slightly more common in men (19.8% vs. 18.9%), although delirium was more common in women (1.9% vs. 0%). In terms of risk factors, the analysis revealed that females were more likely to be obese (36.8% vs. 16.7% in males), while males had higher rates of diabetes (61.1% vs. 51.9% in females), hypertension (69.4% vs. 62.7% in females), and smoking (17.1% vs. 3.8% in females). The findings of this study highlight the differences in dementia risk factors between genders and races, highlighting the need for customized interventions. Furthermore, the registry is a great resource for policymakers and healthcare professionals, providing evidence-based suggestions to improve dementia care, increase the well-being of patients and caregivers, and maximize resource allocation.

The Swiss Memory Clinics recommendations for the treatment of dementia

The Swiss Memory Clinics recommendations for the treatment of dementia

Shoulder Joint Range of Motion Related to Dementia

Introduction: Dementia is caused by various diseases, including Alzheimer’s disease dementia (ADD) and dementia with Lewy bodies (DLB). We often encounter patients with dementia who have limited shoulder joint range of motion (ROM), especially those with behavioral and psychological symptoms of dementia (BPSD). But the relationship between the diseases of dementia and restricted shoulder joint ROM is currently unclear. Methods: We examined cognitive function and shoulder joint ROM in 234 new outpatients at 7 memory clinics in Japan. We assessed cognitive function using the Mini-Mental State Examination (MMSE) and Revised Hasegawa Dementia Scale (HDS-R) and BPSD using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Patients were categorized by dementia diagnosis (ADD, DLB, other dementia, and control). Right, left, and total shoulder joint ROM was assessed using validated the Japanese Orthopaedic Association (JOA) score. Results: We found significant associations of lower right, left, and total shoulder joint ROM scores with male sex, advanced age, higher NPI-Q score, lower HDS-R, and MMSE scores. Little difference was found between right and left shoulder joint ROM scores. Restricted shoulder joint ROM was related to serial 7, verbal frequency domain scores on the HDS-R and repeat score on the MMSE. It was also related to the hallucinations, irritability/lability and nighttime disturbances scores on the NPI-Q. Furthermore, the dementia groups, especially the DLB group, showed worse shoulder joint ROM than the control group. Conclusions: Dementia was significantly related to restricted shoulder joint ROM. Maintaining communication and social interaction may help maintain shoulder joint ROM.

A qualitative study of perceptions of professionals regarding multidisciplinary memory clinics for dementia care

A qualitative study of perceptions of professionals regarding multidisciplinary memory clinics for dementia care

Contribution of a Tablet-Based Tests to the Diagnosis of Neurocognitive Disorders in Older Adults: A Feasibility Study.

Neurocognitive diseases are diagnosed in specialized centers such as memory clinics, where the waiting time can be long. The reference assessment involves a battery of tests carried out by a specialized team. Facilitating screening in primary care using new technologies could make it possible to appropriately direct care pathways towards specialist care. This work aimed to set up a battery of questionnaires, cognitive and manual dexterity tests on a digital tablet to screen people with cognitive impairment. Three groups of people are recruited from a memory consultation: people with major neurocognitive disorders, people with mild neurocognitive disorders and people with no cognitive impairment. Initial results in geriatric settings show that the digital tablet assessment test is feasible and well accepted, but that manual dexterity assessment needs to be adapted to the bodily particularities of the very old.

Diagnostic information in GP referral letters to a memory clinic: a cohort study.

Dementia diagnostics can often be performed in primary care, yet older persons with memory complaints are frequently referred to memory clinics (MCs). To compare diagnostic information in general practitioner (GP) referral letters of patients with and without an eventual dementia diagnosis. Retrospective cohort study in a Dutch academic geriatric MC. We collected electronic health record (EHR) data of consecutive patients aged≥65 referred by their GP between 2016-2020. EHR data included patient characteristics, diagnostic information in referral letters, ancillary investigations performed at the MC, and established diagnoses. Chi-square tests were applied to compare groups. Of 651 patients included, the average age was 78.0 (SD: 6.8), and 348 (53.5%) were diagnosed with dementia. Most people with dementia were diagnosed without ancillary investigations (235/348, 67.5%). In GP referral letters of people with dementia compared with people without dementia, a collateral history, any physical examination, a differential diagnosis including dementia, an MMSE score, interference with daily functioning, and decline from previous levels of functioning were mentioned more often. Furthermore, the more diagnostic criteria mentioned in the referral letter, the more often dementia was diagnosed at the MC (no criteria: 35.4%, one criterion: 47.3%, two criteria: 53.4%, three criteria: 69.9%, four or five criteria: 83.3%). GPs often correctly mention diagnostic information and dementia criteria in referral letters of people with dementia, and they are often diagnosed without ancillary investigations. This suggests that referral is often unnecessary, and GPs can be empowered to diagnose dementia themselves.

Performance of plasma p-tau217 for the detection of amyloid-β positivity in a memory clinic cohort using an electrochemiluminescence immunoassay

BackgroundPlasma p-tau217 has emerged as the most promising blood-based marker (BBM) for the detection of Alzheimer Disease (AD) pathology, yet few studies have evaluated plasma p-tau217 performance in memory clinic settings. We examined the performance of plasma p-tau217 for the detection of AD using a high-sensitivity immunoassay in individuals undergoing diagnostic lumbar puncture (LP).MethodsPaired plasma and cerebrospinal fluid (CSF) samples were analysed from the TIMC-BRAiN cohort. Amyloid (Aβ) and Tau (T) pathology were classified based on established cut-offs for CSF Aβ42 and CSF p-tau181 respectively. High-sensitivity electrochemiluminescence (ECL) immunoassays were performed on paired plasma/CSF samples for p-tau217, p-tau181, Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light (NfL) and total tau (t-tau). Biomarker performance was evaluated using Receiver-Operating Curve (ROC) and Area-Under-the-Curve (AUC) analysis.ResultsOf 108 participants (age: 69 ± 6.5 years; 54.6% female) with paired samples obtained at time of LP, 64.8% (n = 70/108) had Aβ pathology detected (35 with Mild Cognitive Impairment and 35 with mild dementia). Plasma p-tau217 was over three-fold higher in Aβ + (12.4 pg/mL; 7.3—19.2 pg/mL) vs. Aβ- participants (3.7 pg/mL; 2.8—4.1 pg/mL; Mann–Whitney U = 230, p < 0.001). Plasma p-tau217 exhibited excellent performance for the detection of Aβ pathology (AUC: 0.91; 95% Confidence Interval [95% CI]: 0.86–0.97)—greater than for T pathology (AUC: 0.83; 95% CI: 0.75–0.90; z = 1.75, p = 0.04). Plasma p-tau217 outperformed plasma p-tau181 for the detection of Aβ pathology (z = 3.24, p < 0.001). Of the other BBMs, only plasma GFAP significantly differed by Aβ status which significantly correlated with plasma p-tau217 in Aβ + (but not in Aβ-) individuals. Application of a two-point threshold at 95% and 97.5% sensitivities & specificities may have enabled avoidance of LP in 58–68% of cases.ConclusionsPlasma p-tau217 measured using a high-sensitivity ECL immunoassay demonstrated excellent performance for detection of Aβ pathology in a real-world memory clinic cohort. Moving forward, clinical use of plasma p-tau217 to detect AD pathology may substantially reduce need for confirmatory diagnostic testing for AD pathology with diagnostic LP in specialist memory services.

CAPS: a simple clinical tool for β-amyloid positivity prediction in clinical Alzheimer syndrome.

With the advent of anti-β-amyloid therapies, clinical distinction between Aβ + and Aβ- in cognitive impairment is becoming increasingly important for stratifying referral and better utilization of biomarker assays. Cognitive profile, rate of decline, neuropsychiatric inventory questionnaire (NPI-Q), and imaging characteristics were collected from 52 subjects with possible/probable AD. Participants with Aβ+ status had lower baseline MMSE scores (24.50 vs. 26.85, p = 0.009) and higher total NPI-Q scores (2.73 vs. 1.18, p < 0.001). NPI-Q score was found to be the only independent predictor for β-amyloid positivity (p = 0.008). A simple scoring system, namely Clinical β-Amyloid Positivity Prediction Score (CAPS), was developed by using the following parameters: NPI-Q, rapidity of cognitive decline, and white matter microangiopathy. Data from 48 participants were included in the analysis of accuracy of CAPS. CAP Score of 3 or 4 successfully classified Aβ + individuals in 86.7% cases. Clinical β-Amyloid Positivity Prediction Score is a simple clinical tool for use in primary care and memory clinic settings to predict β-amyloid positivity in individuals with clinical Alzheimer Syndrome can potentially facilitate referral for Anti Aβ therapies.

18F-FDG PET can effectively rule out conversion to dementia and the presence of CSF biomarker of neurodegeneration: a real-world data analysis

BackgroundPrecisely defining the delay in onset of dementia is a particular challenge for early diagnosis. Brain [18F] fluoro-2-deoxy-2-D-glucose (18F-FDG) Positron Emission Tomography (PET) is a particularly interesting tool for the early diagnosis of neurodegenerative diseases, through the measurement of the cerebral glucose metabolic rate. There is currently a lack of longitudinal studies under real-life conditions, with sufficient patients, to accurately evaluate the predictive values of brain 18F-FDG PET scans. Here, we aimed to estimate the value of brain 18F-FDG PET for predicting the risk of dementia conversion and the risk of occurrence of a neurodegenerative pathology.MethodsLongitudinal data for a cohort of patients with no diagnosis of dementia at the time of recruitment referred by a tertiary memory clinic for brain 18F-FDG PET were matched with (Prince M, Wimo A, Guerchet Maëlenn, Ali G-C, Wu Y-T et al. World Alzheimer Report 2015. The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. [Research Report] Alzheimer’s Disease International. 2015. 2015.) data from the French National Health Data System (NHDS), (Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–62.) data from the National Alzheimer Bank (NAB), and (Davis M, O`Connell T, Johnson S, Cline S, Merikle E, Martenyi F, et al. Estimating Alzheimer’s Disease Progression Rates from Normal Cognition Through Mild Cognitive Impairment and Stages of Dementia. CAR. 2018;15(8):777–88.) lumbar puncture (LP) biomarker data. The criteria for dementia conversion were the designation, within the three years after the brain 18F-FDG PET scan, of a long-term condition for dementia in the NHDS and a dementia stage of cognitive impairment in the NAB. The criterion for the identification of a neurodegenerative disease in the medical records was the determination of LP biomarker levels.ResultsAmong the 403 patients (69.9 ± 11.4 years old, 177 women) from the initial cohort with data matched with the NHDS data, 137 were matched with the NAB data, and 61 were matched with LP biomarker data. Within three years of the scan, a 18F-FDG PET had negative predictive values of 85% for dementia conversion (according to the NHDS and NAB datasets) and 95% for the presence of LP neurodegeneration biomarkers.ConclusionA normal brain 18F-FDG PET scan can help rule out the risk of dementia conversion and the presence of cerebrospinal fluid (CSF) biomarker of neurodegeneration early with high certainty, allowing modifications to patient management regimens in the short term.Trial registrationClinical Trials database (NCT04804722). March 18, 2021. Retrospectively registered.

Caregiver burden, mental health, quality of life and self-efficacy of family caregivers of persons with dementia in Malaysia: baseline results of a psychoeducational intervention study

BackgroundThe majority of persons with dementia (PWD) are mainly cared for by their family members in the home. Evidence is however scarce on family caregivers’ psychosocial burden and quality of life in Asian countries including Malaysia. This study describes the baseline data of a telephone-delivered psychoeducational intervention study and examines the determinants of outcome measures (caregiver burden, depressive and anxiety symptoms, quality of life and caregiving self-efficacy) among Malaysian family caregivers to PWD.MethodsThis was a cross-sectional study originated from the baseline survey of a randomized control trial of 121 family caregivers recruited from lists of PWD who were registered at memory and psychiatry clinics in three tertiary care hospitals in Malaysia. The participants were assessed for caregiver burden by the Zarit Burden Interview, depressive and anxiety symptoms by the Hospital Anxiety and Depression Scale, quality of life by the Control, Autonomy, Self-Realization, and Pleasure Scale, and caregiving self-efficacy by the Revised Scale for Caregiving Self-Efficacy.ResultsPrevalence of caregiver burden was 69.4%, depressive symptoms 32.2% and anxiety symptoms 32.2%. Family caregivers to PWD having perceived peer support e.g., social/family/friend/significant other supports were less likely to report caregiver burden, depressive and anxiety symptoms, and more likely to report higher levels of quality of life and caregiving self-efficacy. Being married and PWD’s ability to self-care were associated with lesser likelihood of experiencing caregiver burden, depressive and anxiety symptoms. The other determinants of greater probability of reporting better quality of life were caregivers’ employment and having Islamic faith. Marital status (married), PWD’s ability to self-care, spousal relationship with PWD and shared caregiving process were associated with higher likelihood of reporting caregiving self-efficacy.ConclusionCaregiver burden, depressive and anxiety symptoms are prevalent in family caregivers to PWD in Malaysia. Social support and caregiving related factors influence family caregivers’ quality of life and caregiving self-efficacy. Implementing psychoeducational intervention and support in the psychiatry and memory clinics may help improve the psychosocial burden, quality of life and caregiving self-efficacy in family caregivers of PWD.Trial registrationISRCTN14565552 (retrospectively registered).

Real-world performance of plasma p-tau181 in a heterogeneous memory clinic cohort.

In light of clinical trials and disease-modifying therapies, an early identification of patients at-risk of developing Alzheimer's disease (AD) is crucial. Blood-based biomarkers have shown promising results regarding the in vivo detection of the earliest neuropathological changes in AD. Herein, we investigated the ability of plasma p-tau181 to act as a prescreening marker for amyloid positivity in a heterogeneous memory clinic-based cohort. In this retrospective cross-sectional study, we included a total of 115 patients along the clinical AD continuum (mild cognitive impairment [MCI] due to AD, n = 62, probable AD dementia, n = 53). Based on their biomarker status, they were stratified into an amyloid-positive (Aβ+, n = 88) or amyloid-negative cohort (Aβ-, n = 27). Plasma and CSF p-tau181 concentrations were quantified using an ultrasensitive single-molecule array (SIMOA©). Furthermore, age- and sex-adjusted receiver operating characteristic (ROC) curves were calculated and the area under the curve (AUC) of each model was compared using DeLong's test for correlated AUC curves. The median (interquartile range [IQR]) concentration of plasma p-tau181 was significantly higher in Aβ+ patients (3.6 pg/mL [2.5-4.6]), compared with Aβ- patients (1.7 pg/mL [1.2-1.9], p < 0.001). Regarding the distinction between Aβ+ and Aβ- patients and the prediction of amyloid positivity, a high diagnostic accuracy for plasma p-tau181 with an AUC of 0.89 (95% CI = 0.82-0.95) was calculated. Adding the risk factors, age and APOE4, to the model did not significantly improve its performance. Our findings demonstrate that plasma p-tau181 could be a noninvasive and feasible prescreening marker for amyloid positivity in a heterogeneous clinical AD cohort and therefore help in identifying those who would benefit from more invasive assessment of amyloid pathology.

Analysis of individual alpha frequency in a large cohort from a tertiary memory center.

Precise and timely diagnosis is crucial for the optimal use of emerging disease-modifying treatments for Alzheimer disease (AD). Electroencephalography (EEG), which is noninvasive and cost-effective, can capture neural abnormalities linked to various dementias. This study explores the use of individual alpha frequency (IAF) derived from EEG as a diagnostic and prognostic tool in cognitively impaired patients. This retrospective study included 375 patients from the tertiary Memory Clinic of IRCCS San Raffaele Hospital, Milan, Italy. Participants underwent clinical and neuropsychological assessments, brain imaging, cerebrospinal fluid biomarker analysis, and resting-state EEG. Patients were categorized by amyloid status, the AT(N) classification system, clinical diagnosis, and mild cognitive impairment (MCI) progression to AD dementia. IAF was calculated and compared among study groups. Receiver operating characteristic (ROC) analysis was used to calculate its discriminative performance. IAF was higher in amyloid-negative subjects and varied significantly across AT(N) groups. ROC analysis confirmed IAF's ability to distinguish A-T-N- from the A+T+N+ and A+T-N+ groups. IAF was lower in AD and Lewy body dementia patients compared to MCI and other dementia types, with moderate discriminatory capability. Among A+ MCI patients, IAF was significantly lower in those who converted to AD within 2 years compared to stable MCI patients and predicted time to conversion (p < 0.001, R = 0.38). IAF is a valuable tool for dementia diagnosis and prognosis, correlating with amyloid status and neurodegeneration. It effectively predicts MCI progression to AD, supporting its use in early, targeted interventions in the context of disease-modifying treatments.

Clinical utility of diffusion MRI-derived measures of cortical microstructure in a real-world memory clinic setting.

To investigate cortical microstructural measures from diffusion MRI as "neurodegeneration" markers that could improve prognostic accuracy in mild cognitive impairment (MCI). The prognostic power of Amyloid/Tau/Neurodegeneration (ATN) biomarkers to predict progression from MCI to AD or non-AD dementia was investigated. Ninety patients underwent clinical evaluation (follow-up interval 32 ± 18 months), lumbar puncture, and MRI. Participants were grouped by clinical stage and cerebrospinal fluid Amyloid and Tau status. T1-structural and diffusion MRI scans were analyzed to calculate diffusion metrics related to cortical columnar structure (AngleR, ParlPD, PerpPD+), cortical mean diffusivity, and fractional anisotropy. Statistical tests were corrected for multiple comparisons. Prognostic power was assessed using receiver operating characteristic (ROC) analysis and related indices. A progressive increase of whole-brain cortical diffusion values was observed along the AD continuum, with all A+ groups showing significantly higher AngleR than A-T-. Investigating clinical progression to dementia, the AT biomarkers together showed good positive predictive value (with 90.91% of MCI A+T+ converting to dementia) but poor negative predictive value (with 40% of MCI A-T- progressing to a mix of AD and non-AD dementias). Adding whole-brain AngleR as an N marker, produced good differentiation between stable and converting MCI A-T- patients (0.8 area under ROC curve) and substantially improved negative predictive value (+21.25%). Results support the clinical utility of cortical microstructure to aid prognosis, especially in A-T- patients. Further work will investigate other complexities of the real-world clinical setting, including A-T+ groups. Diffusion MRI measures of neurodegeneration may complement fluid AT markers to support clinical decision-making.

Capturing Usability Problems for People Living With Dementia by Applying the DEMIGNED Principles in Usability Evaluation Methods: Mixed Methods Study.

Dementia-related impairments can cause complex barriers to access, use, and adopt digital health technologies (DHTs). These barriers can contribute to digital health inequities. Therefore, literature-based design principles called DEMIGNED have been developed to support the design and evaluation of DHTs for this rapidly increasing population. This study aims to apply the DEMIGNED principles in usability evaluation methods to (1) capture usability problems on a mobile website providing information resources for people visiting a memory clinic, including those living with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia, and (2) investigate the realness of usability problems captured by the DEMIGNED principles in expert testing, specifically for mobile websites that act as a means of providing DHTs. First, a heuristic evaluation was conducted, with the DEMIGNED principles serving as domain-specific guidelines, with 3 double experts (experienced in both usability and dementia) and 2 usability engineering experts. Second, think-aloud sessions were conducted with patients visiting a memory clinic who were living with SCD, MCI, or dementia. The heuristic evaluation resulted in 36 unique usability problems. A representative sample of 7 people visiting a memory clinic participated in a think-aloud session, including 4 (57%) with SCD, 1 (14%) with MCI, and 2 (29%) with dementia. The analysis of the think-aloud sessions revealed 181 encounters with usability problems. Of these encounters, 144 (79.6%) could be mapped to 18 usability problems identified in the heuristic evaluation. The remaining 37 (20.4%) encounters from the user testing revealed another 10 unique usability problems. Usability problems frequently described in the think-aloud sessions encompassed difficulties with using the search function, discrepancies between the user's expectations and the content organization, the need for scrolling, information overload, and unclear system feedback. By applying the DEMIGNED principles in expert testing, evaluators were able to capture 79.6% (144/181) of all usability problem encounters in the user testing of a mobile website for people visiting a memory clinic, including people living with dementia. Regarding unique usability problems, 50% (18/36) of the unique usability problems identified during the heuristic evaluation were captured by the user-testing sessions. Future research should look into the applicability of the DEMIGNED principles to other digital health functionalities to increase the accessibility of digital health and decrease digital health inequity for this complex and rapidly increasing population.

Sensorimotor Impairment in Aging and Neurocognitive Disorders: Beat Synchronization and Adaptation to Tempo Changes.

Understanding the nature and extent of sensorimotor decline in aging individuals and those with neurocognitive disorders (NCD), such as Alzheimer's disease, is essential for designing effective music-based interventions. Our understanding of rhythmic functions remains incomplete, particularly in how aging and NCD affect sensorimotor synchronization and adaptation to tempo changes. This study aimed to investigate how aging and NCD severity impact tapping to metronomes and music, with and without tempo changes. Patients from a memory clinic participated in a tapping task, synchronizing with metronomic and musical sequences, some of which contained sudden tempo changes. After exclusions, 51 patients were included in the final analysis. Participants' Mini-Mental State Examination scores were associated with tapping consistency. Additionally, age negatively influenced consistency when synchronizing with a musical beat, whereas consistency remained stable across age when tapping with a metronome. The results indicate that the initial decline of attention and working memory with age may impact perception and synchronization to a musical beat, whereas progressive NCD-related cognitive decline results in more widespread sensorimotor decline, affecting tapping irrespective of audio type. These findings underline the importance of customizing rhythm-based interventions to the needs of older adults and individuals with NCD, taking into consideration their cognitive as well as their rhythmic aptitudes.