Alzheimer's Disease Dementia Research Articles

Ten Reasons Why Neurologists Should Refer Patients With Alzheimer Dementia to Music Therapy.

Alzheimer dementia (AD) constitutes a major societal problem with devastating neuropsychiatric involvement. Pharmaceutical interventions carry a heightened risk of side effects; thus, nonpharmacological interventions such as music-based interventions (MBIs), including music therapy, are recommended. The 2023 Neurology release of the Music Based Intervention Toolkit for Brain Disorders of Aging showcased music's emerging role as an intervention to manage symptoms of various brain disorders while defining the building blocks of MBIs to guide research in the exploration of music's therapeutic potential. This study extends beyond the research aspects of the MBI Toolkit to clinical applications by providing neurologists with a summary of MBIs, the MBI Toolkit, how board-certified music therapists (MT-BCs) administered music therapy is a unique MBI, and 10 reasons why they should make referrals to music therapy for their patients with AD.

Utility of Tau PET in the diagnostic work up of neurodegenerative dementia among Indian patients

Background and objectivesTau PET is being increasingly appraised as a novel diagnostic modality for dementia work up. Given limited data among South Asians, we assessed the frequency, patterns, phenotypic associations and incremental value of positive Tau PET scans in clinically diagnosed neurodegenerative dementia. MethodsThis cross-sectional study recruited consecutive patients of Alzheimer's disease (AD) and non-AD syndromes (September 2021 to October 2022, India). Participants underwent clinical interview, cognitive assessment, MRI brain and tau PET scan ([F-18]ML-104). Visual read in a priori regions of interest was used to identify patterns of tau deposition in the brain. ResultsWe recruited 54 participants (mean age: 63.2 ± 9.2 years, 70.4 % men, 77.8 % dementia, 70.4 % early onset cases, 37.8 % APOE4+). The analysis identified abnormal tau uptake in 40/54 (74.1 %) participants; with uptake in AD signature areas in 27/40 (67.5 %) cases [cortical subtype (74.1 %), limbic (14.8 %), combined cortical/limbic (11.1 %)], and patterns not conforming to AD in 13/40 (32.5 %) cases. Tau PET substantiated the diagnosis of AD among 17/19 (89.5 %) cases with clinically diagnosed AD dementia, 8/23 (34.8 %) cases with suspected non-AD cause, and 2/12 (16.7 %) cases with mild cognitive impairment. A trend for increasing proportion of early onset cases, and worsening cognition, behavior and functional ability was seen, from ‘limbic’ to ‘combined cortical/limbic’ to ‘cortical’ subgroups. ConclusionTau PET is a useful modality to differentiate AD dementia from other neurodegenerative causes in the Indian setting where amyloid biomarkers are not widely available. Biological subtypes of AD map well onto clinical phenotypes and need study in larger cohorts.

Baseline-dependent enhancement of working memory by memantine in male rats: Involvement of NMDA receptor subunits and CaMKII signaling

N-methyl-d-aspartate (NMDA) receptors, activated by glutamate, play a crucial role in learning and memory. Memantine (MEM), a non-competitive NMDA receptor antagonist, is currently prescribed for the treatment of Alzheimer's disease or dementia, which meanwhile simultaneously promotes a need to clarify its potential pro-cognitive effects that exist in normal healthy individuals. However, the neurobehavioral mechanisms underlying the cognitive improvement by MEM in normal individuals remain to be elucidated. This study aimed to assess the effects of MEM on working memory, measured by a discrete paired-trial delay alternation task in a T-maze in normal male rats. The impacts of MEM were hypothesized to vary depending on different baseline levels of working memory performance. Neurochemical examination of the levels of calcium/calmodulin-dependent kinase 2 (CaMKII) and NMDA receptor subunits within five targeted brain regions was conducted after behavioral tests. The results showed that acute administration of MEM enhanced working memory performance, with 2.5, 5.0, and 10 mg/kg doses increasing task accuracy compared to the vehicle, particularly in low performers. Neurochemically, the protein expression of CaMKII in the amygdala and that of the glutamate (Glu) N2A subunit in the dorsal striatum were greater in the low-performance group than in the high-performance group. Additionally, the protein expression of the GluN2A subunit in the dorsal striatum was negatively associated with task performance at baseline. The expression of GluN1 and GluN2B in the nucleus accumbens was negatively associated with task performance in the retest three weeks after drug treatment. These findings underscore the baseline-dependent improvement of working memory resulting from MEM administration, with observed drug effects associated with alterations in the levels of NMDA receptor subunits in striatal subareas and CaMKII in the amygdala.

Lecanemab Planning: Blueprint for Safe and Effective Management of Complex Therapies.

Approximately 6.9 million American individuals have Alzheimer dementia and 50% have mild disease. Lecanemab, an approved antiamyloid antibody, is associated with modest reduction in functional decline in patients with mild dementia or mild cognitive impairment. In Clarity-AD, 239 (26.6%) of patients experienced amyloid-related imaging abnormalities (ARIAs) overall (i.e., ARIAs associated with hemorrhages or edema). The complexity of treatment and risks of adverse events necessitate a multidisciplinary collaborative approach. With limited treatment options, lecanemab approval generated significant interest among clinicians, patients, and families. Lecanemab treatment requires biweekly infusions along with ongoing imaging tests, laboratory monitoring, patient assessment, drug interaction screening, and cognitive function monitoring. Processes to support patient selection, access, and safety are important given the monitoring requirements and total cost of care. The planning process for lecanemab can serve as a blueprint to support safe and effective management of therapeutic innovation in neurology and other areas.

Risk factors for Alzheimer's disease and related dementias in U.S. honor cultures

Risk factors for Alzheimer's disease and related dementias in U.S. honor cultures

Communication Bridge-2 randomized controlled trial: Recruitment and baseline features.

Non-pharmacological interventions may offer significant benefits to the quality of life for persons with primary progressive aphasia (PPA) and their care partners but have lacked efficacy trials. To help fill the efficacy gap, we provide the feasibility of recruitment, enrollment, randomization, and baseline data for the Communication Bridge-2 (CB2) randomized controlled trial (RCT). CB2 is the first international, single enrollment site, Phase 2, Stage 2, parallel-group, active control, RCT delivered via video chat to individuals with PPA and their care partners. Participants were recruited, screened, and randomized into one of two speech-language intervention arms. Ninety-five participant dyads (PPA mean baseline age: 67.1; 48% female) from four countries were enrolled and randomized. Global recruitment, enrollment, and randomization of individuals with PPA into a video chat-delivered non-pharmacologic RCT is feasible. This trial provides a potential model for conducting rigorous non-pharmacologic efficacy trials for Alzheimer's disease and related dementias. Primary progressive aphasia (PPA) negatively impacts communication participation. Communication Bridge-2 (CB2) is a telemedicine-delivered randomized controlled trial. CB2 included global recruitment and randomization of 95 PPA participant dyads. CB2, the first international superiority trial for PPA using video chat shows feasibility. The study provides a model for rigorous non-pharmacologic trials for Alzheimer's disease and related dementias.

The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI).

The presence of multiple pathologies is the largest predictor of dementia. A major gap in the field is the in vivo detection of mixed pathologies and their antecedents. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address this gap. The ADRCs longitudinally follow ≈ 17,000 participants, ranging from cognitively unimpaired to dementia, arising from Alzheimer's disease (AD) and related dementias (ADRD; e.g., AD, Lewy body disorders, vascular). Motivated by the Alzheimer's Disease Neuroimaging Initiative's (ADNI) impact, the ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) was formed. Leveraging existing ADRC infrastructure, CLARiTI will integrate standardized imaging and plasma collection to characterize mixed pathologies and use community-engaged research methods to ensure that≥ 25% of the sample is from underrepresented populations (e.g., ethnoculturally minoritized, low education). The resulting ADRD profiles, within a more diverse sample, will provide key resources for ADRCs and an unprecedented, more generalizable publicly available imaging-plasma dataset. HIGHLIGHTS: In vivo detection of mixed pathologies is critical for Alzheimer's disease and related dementias research. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address gaps related to mixed pathologies. The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will enhance this national program by adding standardized imaging and plasma collection to existing ADRC infrastructure. This effort will provide key resources for ADRCs and an unprecedented publicly available imaging-plasma-neuropath dataset.

Impact of white matter hyperintensity volume on cognition among US Mexican American adults.

Higher white matter hyperintensity (WMH) volume is a marker of cardiovascular disease (CVD) risk. CVD risk factors increase risk for Alzheimer's disease and related dementias (ADRD). Mexican Americans (MA) and individuals of other Hispanic/Latino heritages have higher risk for CVD and ADRD. However, knowledge of associations between WMH volume and cognition in these groups remains limited. We conducted a cross-sectional study of associations between WMH volume and neuropsychological performance (attention/executive functioning, memory) in MA (n = 851) and non-Hispanic White (NHW; n = 747) adults in the Health and Aging Brain Study: Health Disparities. The MA group (mean age = 63.72 ± 7.90 years; 66.3% female) had higher rates of consensus diagnoses of hypertension and diabetes, whereas the NHW group (mean age = 69.18 ± 8.65 years; 55.2% female) had higher rates of diagnosed CVD (ps < .01). WMH volumes were higher among individuals with CVD risk factors/conditions (ps < .01). There were differential associations between WMH and neuropsychological performance across ethnoracial groups (ps < .001), wherein associations were steeper in the NHW group than in the MA group. Lower educational level was associated with higher WMH volume in the NHW group (p < .001), but no association was seen in the MA group (p > .05). Negative effects of pathological changes in the form of WMH on cognition may be less robust or consistent for MA adults than NHW adults. Furthermore, the impact of WMH on cognition in NHW adults may be mitigated by cognitive reserve related to educational attainment.

Clinical and biological underpinnings of longitudinal atrophy pattern progression in Alzheimer's disease.

Magnetic resonance imaging (MRI) has recently enabled to identify four distinct Alzheimer's disease (AD) subtypes: hippocampal sparing (HpSp), typical AD (tAD), limbic predominant (Lp), and minimal atrophy (MinAtr). To date, however, the natural history of these subtypes, especially regarding the presence of subjects switching to other MRI patterns and their clinical and biological differences, remains poorly understood. To investigate the clinical and biological underpinnings of longitudinal atrophy pattern progression in AD. 251 AD patients (16 with significant memory concern, 66 with early mild cognitive impairment (MCI), 125 with late MCI, and 44 with AD dementia) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were assigned to their baseline MRI atrophy subtype using Freesurfer-derived cortical:hippocampal volumes ratio. Switching to other MRI patterns was investigated on longitudinal scans, and patients were accordingly classified as "switching" and "stable". Logistic regression models were applied to identify predictors of switching to other MRI patterns. 40% of Lp, 26% of HpSp, and 35% of MinAtr cases switched to other MRI patterns, with tAD representing the destination subtype of all switching HpSp and Lp, and the majority of MinAtr. At baseline significant clinical, cognitive and biomarkers differences were observed across the four subtypes. Only clinical and cognitive variables, however, were significantly associated with switch to other MRI patterns. Our results suggest convergent directions of disease progression across atypical and typical AD forms, at least in a subset of AD subjects, and highlight the importance of deep-phenotyping approaches to understand AD heterogeneity.

Identification and cognitive function prediction of Alzheimer's disease based on multivariate pattern analysis of hippocampal volumes.

Alzheimer's disease (AD) is strongly associated with slowly progressive hippocampal atrophy. Elucidating the relationships between local morphometric changes and disease status for early diagnosis could be aided by machine learning algorithms trained on neuroimaging datasets. This study intended to propose machine learning models for the accurate identification and cognitive function prediction across the AD severity spectrum based on structural magnetic resonance imaging (sMRI) of the bilateral hippocampi. The high-resolution sMRI data of 120 AD dementia patients, 232 amnestic mild cognitive impairment (aMCI) patients, and 206 healthy controls (HCs) were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The classification capacity and cognitive predict ability of hippocampal volume was evaluated by multiple pattern analysis using the support vector machine (SVM) and relevance vector regression (RVR) application of the Pattern Recognition for Neuroimaging Toolbox, separately. For validation, the analyses were performed using a biomarker-based regrouping method and another independent local dataset. The SVM application produced a total accuracy of 94.17%, 80.85%, and 70.74% and area under receiver operating characteristic curves of 0.97, 0.87, and 0.72 between HC versus AD dementia, HC versus aMCI, and aMCI versus AD dementia classification, respectively. The RVR application significantly predicted the baseline and mean cognitive function at three years of follow-up. Qualitatively consistent results were obtained using different regrouping method and the local dataset. The machine learning methods based on the bilateral hippocampi distinguished across the AD severity spectrum and predicted the baseline and the longitudinal cognitive function with greater accuracy.

Divergent neurodegenerative patterns: comparison of fluorodeoxyglucose-PET and MRI-based Alzheimer’s disease subtypes

Abstract [18F] fluorodeoxyglucose (FDG)-PET and MRI are key imaging markers for neurodegeneration in Alzheimer's disease. It has been well established that parieto-temporal hypometabolism on FDG-PET is closely associated with medial temporal atrophy on MRI in Alzheimer's disease. Substantial biological heterogeneity, expressed as distinct subtypes of hypometabolism or atrophy patterns, has been previously described in Alzheimer's disease using data-driven and hypothesis-driven methods. However, the link between these two imaging modalities has not yet been explored in the context of Alzheimer's disease subtypes. To investigate this link, the current study utilised FDG-PET and MRI scans from 180 amyloid-beta positive Alzheimer's disease dementia patients, 339 amyloid-beta positive mild cognitive impairment and 176 amyloid-beta negative cognitively normal controls from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Random forest hierarchical clustering, a data-driven model for identifying subtypes, was implemented in the two modalities: one with standard uptake value ratios and the other with grey matter volumes. Five hypometabolism- and atrophy-based subtypes were identified, exhibiting both cortical-predominant and limbic-predominant patterns although with differing percentages and clinical presentations. Three cortical-predominant hypometabolism subtypes found were: Cortical Predominant (32%), Cortical Predominant+ (11%), Cortical Predominant posterior (8%); and two limbic-predominant hypometabolism subtypes: Limbic Predominant (36%) and Limbic Predominant frontal (13%). In addition, little atrophy (minimal) and widespread (diffuse) neurodegeneration subtypes were observed from the MRI data. The five atrophy subtypes were found: Cortical Predominant (19%), Limbic Predominant (27%), Diffuse (29%), Diffuse+ (6%) and Minimal (19%). Inter-modality comparisons showed that all FDG-PET subtypes displayed medial temporal atrophy, whereas the distinct MRI subtypes showed topographically similar hypometabolic patterns. Further, allocations of FDG-PET and MRI subtypes were not consistent when compared at an individual-level. Additional analysis comparing the data-driven clustering model with prior hypothesis-driven methods showed only partial agreement between these subtyping methods. FDG-PET subtypes had greater differences between limbic-predominant and cortical-predominant patterns and MRI subtypes had greater differences in severity of atrophy. In conclusion, this study highlighted that Alzheimer's disease subtypes identified using both FDG-PET and MRI capture distinct pathways showing cortical- versus limbic-predominance of neurodegeneration. However, the subtypes do not share a bidirectional relationship between modalities and are thus not interchangeable.

Benchmarking of a multi-biomarker low-volume panel for Alzheimer's disease and related dementia research.

In the research setting, obtaining accurate established biomarker measurements and maximizing use of the precious samples is key. Accurate technologies are available for Alzheimer's disease (AD), but no platform can measure all the established and emerging biomarkers in one run. The NUcleic acid Linked Immuno-Sandwich Assay (NULISA) is a technology that requires 15µL of sample to measure more than 100 analytes. We compared AD-relevant biomarkers included in the NULISA against validated assays in cerebrospinal fluid (CSF) and plasma. CSF measures of amyloid beta 42/40, and phosphorylated tau (p-tau)217 are highly correlated when measured by immunoassay, mass spectrometry, or NULISA. In plasma, p-tau217 performance is similar to that reported with other technologies when predicting amyloidosis. Other biomarkers show a wide range of correlation values depending on the fluid and the platform. The NULISA multiplexed platform produces reliable results for established biomarkers in CSF that are useful in research settings, with the advantage of measuring additional biomarkers using minimal sample volume. We tested the novel technology NUcleic acid Linked Immuno-Sandwich Assay (NULISA) in the dementia research setting. NULISA multiplexed platform produces reliable results for established and emerging biomarkers using minimal sample volume. Cerebrospinal fluid measures of amyloid beta 42/40, and phosphorylated tau (p-tau)217 are highly correlated when measured by immunoassay, mass spectrometry, or NULISA. In plasma, p-tau217 performance is similar to that reported with other technologies when predicting amyloidosis. NULISA measures are useful in research settings, with the advantage of measuring additional biomarkers using minimal sample volume.

Cognitive Intra-individual Variability in Cognitively Healthy APOE ε4 Carriers, Mild Cognitive Impairment, and Alzheimer's Disease: a Meta-analysis.

Intra-individual variability (IIV) quantifies an individual's scatter in performances across a test battery (dispersion) or across reaction times within a single task (consistency). No studies have meta-analyzed the cross-sectional IIV literature in those with mild cognitive impairment (MCI) and Alzheimer's dementia (AD). An additional aim of this meta-analysis was to examine IIV in APOE ε4 + healthy control (HC) samples. A systematic search strategy was applied to six databases (Academic Search Complete, PsycINFO, MEDLINE, CINAHL Complete, ERIC, and ProQuest Dissertations & Theses) to identify studies comparing the extent of dispersion- and consistency-based cognitive IIV between clinical (MCI, AD) and HC samples. Thirty-five studies met the inclusion criteria for our random-effects cross-sectional meta-analysis. Hedges' g was used to aggregate between-group effect sizes, with higher positive values indicating clinical > HC IIV. Meta-regression and subgroup-analyses were conducted to evaluate continuous and categorical moderator variables, respectively. Omnibus models yielded analogous moderate-strength, albeit heterogeneous, effects for dispersion and consistency (g = 0.65). Clinical severity was a robust moderator of dispersion (MCI = 0.47, AD = 1.16) and consistency (MCI = 0.51, AD = 1.31) effects. Supplemental analysis of APOE ε4 status in HCs revealed a nonsignificant trend of elevated overall (i.e., dispersion + consistency) IIV in APOE ε4 + vs. APOE ε4 - HC samples (g = 0.24). Cognitive IIV is sensitive to the presence of AD-related genetic risk as well as neurocognitive impairment across the neurocognitive disorder severity spectrum, with a graded-pattern of HC < MCI < AD samples.

Diets to promote healthy brain ageing.

Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical trials regarding the potential role of diet in theprevention of cognitive decline and dementia. We further discuss possible methodological limitations that might have hindered the ability of previous diet intervention trials to capture potential neuroprotective effects. Considering the overwhelming and continuously expanding societal, economic and health-care burden of Alzheimer disease and other dementias, future nutritional research must address past methodological challenges to accurately and reliably inform clinical practice guidelines and public health policies. Within this scope, we provide a roadmap for future diet intervention trials for dementia prevention. We discuss study designs involving both intensive personalized interventions - to evaluate pharmacokinetic and pharmacodynamic properties, establish neuroprotective thresholds, and test hypothesized biological mechanisms and effects on brain health and cognition through sensitive and precise biomarker measures - and large-scale, pragmatic public health interventions to study population-level benefits.

A Mindfulness-Based Lifestyle Intervention for Dementia Risk Reduction: Protocol for the My Healthy Brain Feasibility Randomized Controlled Trial.

Lifestyle behavior change and mindfulness have direct and synergistic effects on cognitive functioning and may prevent Alzheimer disease and Alzheimer disease-related dementias (AD/ADRD). We are iteratively developing and testing My Healthy Brain (MHB), the first mindfulness-based lifestyle group program targeting AD/ADRD risk factors in older adults with subjective cognitive decline. Our pilot studies (National Institutes of Health [NIH] stage 1A) have shown that MHB is feasible, acceptable, and associated with improvement in lifestyle behavior and cognitive outcomes. We will compare the feasibility of MHB versus an education control (health enhancement program [HEP]) in 50 older adults (aged ≥60 y) with subjective cognitive decline and AD/ADRD risk factors. In an NIH stage 1B randomized controlled trial (RCT), we will evaluate feasibility benchmarks, improvements in cognitive and lifestyle outcomes, and engagement of hypothesized mechanisms. We are recruiting through clinics, flyers, web-based research platforms, and community partnerships. Participants are randomized to MHB or the HEP, both delivered in telehealth groups over 8 weeks. MHB participants learn behavior modification and mindfulness skills to achieve individualized lifestyle goals. HEP participants receive lifestyle education and group support. Assessments are repeated after the intervention and at a 6-month follow-up. Our primary outcomes are feasibility, acceptability, appropriateness, credibility, satisfaction, and fidelity benchmarks. The secondary outcomes are cognitive function and lifestyle (physical activity, sleep, nutrition, alcohol and tobacco use, and mental and social activity) behaviors. Data analyses will include the proportion of MHB and HEP participants who meet each benchmark (primary outcome) and paired samples 2-tailed t tests, Cohen d effect sizes, and the minimal clinically important difference for each measure (secondary outcomes). Recruitment began in January 2024. We received 225 inquiries. Of these 225 individuals, 40 (17.8%) were eligible. Of the 40 eligible participants, 21 (52.5%) were enrolled in 2 group cohorts, 17 (42.5%) were on hold for future group cohorts, and 2 (5%) withdrew before enrollment. All participants have completed before the intervention assessments. All cohort 1 participants (9/21, 43%) have completed either MHB or the HEP (≥6 of 8 sessions) and after the intervention assessments. The intervention for cohort 2 (12/21, 57%) is ongoing. Adherence rates for the Garmin Vivosmart 5 (128/147, 87.1% weeks) and daily surveys (105/122, 86.1% weeks) are high. No enrolled participants have dropped out. Enrollment is projected to be completed by December 2024. The RCT will inform the development of a larger efficacy RCT (NIH stage 2) of MHB versus the HEP in a more diverse sample of older adults, testing mechanisms of improvements through theoretically driven mediators and moderators. The integration of mindfulness with lifestyle behavior change in MHB has the potential to be an effective and sustainable approach for increasing the uptake of AD/ADRD risk reduction strategies among older adults. ClinicalTrials.gov NCT05934136; https://www.clinicaltrials.gov/study/NCT05934136. DERR1-10.2196/64149.

Quantitative Imaging of Regional Cerebral Protein Synthesis in Clinical Alzheimer's Disease by [11C]Leucine PET.

Protein synthesis is essential to maintain integrity and function of the human brain, and protein synthesis is associated specifically with the formation of long-term memory. Experimental and clinical observations indicate that this process is disturbed in Alzheimer's dementia and other neurodegenerative diseases. In-vivo investigation with positron emission tomography (PET) using [11C]leucine provides a unique possibility to measure regional cerebral protein synthesis (rCPS) rates in human brain and to determine whether it is altered in Alzheimer's disease (AD), and thus may provide a target for future therapeutic interventions. In this first human study, we measured rCPS by [11C]leucine PET in four patients with AD (age 57-73years) and compared the results with six healthy controls (three of whom were age matched and the other three were young controls). Quantification of rCPS also required measurement of amino acid (AA) levels and of free and protein-bound [11C]leucine in plasma during the 90min PET scans conducted following at least six hours of fasting. Rates of rCPS measured in absolute units of nmol/g/min ranged between 1.81 and 2.53 in AD patients, 2.10 and 2.54 in matched controls, and 2.21 to 2.35 in the young controls. Mean and median values did not show significant differences between the groups. Rates of rCPS also depended upon whether corrections for plasma AA levels were included in the calculations. When considering regional values relative to the corpus callosum as a reference region, there was a tendency towards impairment of rCPS in patients, which was most prominent in the parietal cortex, but did not reach significance. Similar findings were observed with normalisation of rCPS to global cortical mean. In summary, this first human study assessing regional protein synthesis with [11C]leucine in AD has demonstrated where the sources of variance in measurements of cerebral protein synthesis may arise, along with the potential magnitude of this variance. This study also indicates that there is a tendency towards impairment of rCPS in patients with Alzheimer's disease, which requires further investigation including possible partial volume effects due to atrophy.

Conversion to Alzheimer's disease dementia from normal cognition directly or with the intermediate mild cognitive impairment stage.

Progression to Alzheimer's disease (AD) dementia from normal cognition (NC) can follow different trajectories, with most progressing through a recognizable mild cognitive impairment stage (NC-MCI-AD), while some individuals transition quickly from NC to AD dementia (NC-AD). We compared demographic characteristics, health factors, and cognitive and functional assessments across three time points: the first NC visit, the last NC visit, and the first AD dementia visit. The NC-MCI-AD group showed greater impairment in cognitive and functional scores at AD dementia diagnosis, despite maintaining better cognitive function during the NC stage. Analysis of yearly changes revealed negligible differences during NC. However, the yearly change during the AD dementia stage suggested potentially more rapid functional decline in the NC-AD group. These findings highlight the heterogeneity in AD disease progression and emphasize the importance of considering diverse progression patterns in AD research and clinical practice. We investigated the disease progression difference between patients who converted to Alzheimer's disease (AD) dementia from normal cognition (NC) directly or through the mild cognitive impairment (MCI) stage. We found that the NC-MCI-AD group showed greater impairment in cognitive and functional scores at AD dementia diagnosis. We discovered that the NC-AD group had rapid functional decline once patients were confirmed with AD onset.

Personality Phenomena in Women with Alzheimer’s Dementia

State-of-the-art literature has been enhancing the significance of personality phenomena in Alzheimer’s dementia (AD). This study seeks to identify the relationships of current and premorbid traits and abnormal dimensions in AD. Five-factor model and axis II personality disorders are taken as references. This research was conducted with two groups, which were assessed using the NEO-FFI and PDQ-4+ in individual interview sessions. Current personality measure: AD Group (n = 44 female participants); premorbid personality measure: AD group informants (n = 40 related participants). Findings suggest that in terms of both premorbidity and current studies, the relevance of the dimensions neuroticism (high) and conscientiousness (low), are the most common explanations found in the personality disorder scales, DSM clusters, Appendix B and the global personality disorder index. These data are relevant for the assessment of personality phenomena in Alzheimer’s disease.

Marmosets as model systems for the study of Alzheimer's disease and related dementias: Substantiation of physiological tau 3R and 4R isoform expression and phosphorylation.

Marmosets spontaneously develop pathological hallmarks of Alzheimer's disease (AD) including amyloid beta plaques. However, tau expression in the marmoset brain has been understudied. Isoforms of tau were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining. 3R and 4R tau isoforms are expressed in marmoset brains at both the transcript and protein levels across ages. Mass spectrometry analysis revealed that tau peptides in marmoset corresponded to the 3R and 4R peptides in human brain, with 3R predominating at birth and an ≈40%:60% 3R:4R ratios in adolescents and adults; tau was distributed widely in neurons, with localization in the soma and synaptic regions. Phosphorylation residues were observed on Threonine (Thr) Thr181, Thr217, Thr231, Serine (Ser) Ser202/Thr205, and Ser396/Ser404. Our results confirm both 3R and 4R tau isoform expression and phosphorylation residues in the marmoset brain, and emphasize the significance of marmosets with natural expression of AD-related hallmarks as important translational models for AD. Highlights We report comprehensive characterization of tau isoform expression in marmoset brains across the lifespan. 3R and 4R tau isoforms are expressed in marmoset brains at both the transcript and protein levels across ages. These data emphasize the significance of marmosets with natural expression of primate-specific traits that are important for the study of Alzheimer's disease.

Impact of diabetes mellitus on the risk of Alzheimer’s disease: a mendelian randomization study

BackgroundThe impact of diabetes on the risk of Alzheimer’s disease remains uncertain. This study aimed to explore this issue from multiple perspectives by using the Mendelian randomization (MR) approach.MethodsInstrumental variables for predicting six diabetic traits (including insulin and blood glucose), eight metabolic risk factors for diabetes (including total cholesterol and blood pressure), and seven diabetic genes were extracted from their summary data. These data were derived from multiple European cohorts and included 31,684 to 810,865 subjects respectively. The two-sample MR, multivariate MR, and summary-data-based Mendelian randomization (SMR) methods were employed to determine the associations of these traits or genes with the risk of Alzheimer’s disease.ResultsThe two-sample MR showed that elevated fasting insulin and total cholesterol levels were associated with an increased risk of dementia in Alzheimer’s disease (P = 0.022, P = 0.041). Elevated systolic and diastolic blood pressure levels were associated with a decreased risk of dementia in Alzheimer’s disease (P = 0.036, P = 0.025). The multivariate MR reported that adjusting for telomere length (a well-established biomarker of aging) did not change these findings (P < 0.05). Additionally, the two-sample MR showed that type 1 and type 2 diabetes did not affect the risk of Alzheimer’s disease. The SMR also indicated that the diabetic genes did not affect the risk of this disease.ConclusionMultiple MR approaches concluded that fasting insulin, total cholesterol, and blood pressure, rather than diabetes, were potential metabolic variables that had an impact on the risk of Alzheimer’s disease. However, aging might not be involved in these correlations.