bluuebunny/crossref_metadata_2025 huggingface dataset:
The effectiveness of a personalised multidomain lifestyle intervention programme to slow cognitive decline: study protocol for a series of randomised open‐label N‐of‐1 trials
Authors: Chong Wayne Freeman , Kandiah Nagaendran , Azam Mohammed Adnan
Published: January 2025

Background

Multidomain lifestyle interventions for dementia risk reduction have been developed and trialled because reversible lifestyle factors have been shown to contribute to the onset and progression of dementia. A recent review and meta‐analysis confirmed small beneficial effects of such interventions on cognitive performance. To enhance the effectiveness of these interventions, we have developed and incorporated personalisation approaches. This study aims to investigate the effectiveness of a personalised multidomain lifestyle intervention programme in slowing cognitive decline.

Method

A series of randomised open‐label trials in a single research participant (N‐of‐1 trials) will be conducted with 100 participants who are 50 years and over, and with mild cognitive impairment (MCI) and cerebral small vessel disease (CSVD). These participants will be recruited from an ongoing panel study that evaluates global and specific cognition, demographic, behavioural and vascular risk characteristics, lifestyle habits, blood‐based biomarkers and brain structure, among community dwelling Singapore residents. With a multiple baseline design situated within a 12‐week period, the baseline duration for each participant will vary systematically and randomly (Figure A). Baseline measurements should appear stable before each participant starts the intervention. The intervention is a 24‐week programme in which a study clinician reviews available baseline data, discloses the MCI and CSVD classification, provides standard cognitive health education electronically, communicates a dementia risk score via the use of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score App, discusses and recommends lifestyle activities involving some combination of a tailored exercise regimen, gamified digital cognitive activities, and nutritional guidance, with intensity personalized according to the baseline vascular risk characteristics and CSVD burden of each participant, and provides behavioural counselling utilising cognitive‐behavioural and motivational strategies. Adherence to the lifestyle activities will be assessed fortnightly using wearable trackers, in‐game cognitive assessments, and a digital food diary respectively.

Result

Global cognition at 24 weeks and at 1‐, 3‐ and 6‐month follow‐up will be compared with baseline global cognition for each participant. Data aggregation could uncover response characteristics across individuals (Figure B).

Conclusion

Meta‐analyses would provide high quality evidence of the intervention’s effectiveness at the individual and the population levels.
Characteristics of cerebrospinal fluid biomarkers/ imaging findings in patient with amyloid‐negative dementia ∼second report∼
Authors: Takenoshita Naoto , Inagawa Shoya , Yamamoto Ryo , Hanyu Haruo , Kasuga Kensaku , Ikeuchi Takeshi , Ishii Kenji , Shimizu Soichiro
Published: January 2025

Background

In daily clinical practice, we often encounter cases with atypical symptoms and imaging findings, even among those diagnosed with Alzheimer's disease. Amyloid PET and cerebrospinal fluid examinations were performed in such non‐typical cases and young cases.

Method

A total of 85 patients underwent both amyloid PET and cerebrospinal fluid examinations. The amyloid PET results were divided into two groups, amyloid‐positive group (n=43) and amyloid‐negative group (n=42) based on the visual judgment criteria of Japanese‐ADNI. Neuropsychological tests, MRI findings, cerebral blood flow SPECT findings, and cerebrospinal fluid findings were compared between the two groups.

Result

CSF findings showed significant differences in Aβ42, Aβ42/40 and P‐tau between the two groups. MRI findings showed no significant differences in medial temporal lobe atrophy and cerebral white matter lesion between the two groups. Cerebral blood flow SPECT findings showed a significant difference in decreased blood flow in the right parietal lobe and bilateral precuneus between the two group.

Conclusion

In dementia patients with atypical clinical symptoms/imaging findings, cerebrospinal fluid findings and decreased blood flow in the right parietal lobe and bilateral precuneus are used to investigate whether amyloid is involved in the background pathology.
Policy & Organizational Factors that Affect the Utilization of Health Services for Alzheimer’s Disease Among the Latinx Community – The Primary Care Provider Perspective
Authors: Pinzon Maria C Mora , Garcia Diana C Martinez , Perales Jaime
Published: January 2025

Background

Latinx individuals bear a disproportionate burden of Alzheimer’s disease and related dementias (ADRD), with higher risk, underdiagnosis, and limited access to quality care. Primary care providers (PCPs) are crucial for early detection and management, yet organizational and policy factors significantly impact their ability to provide culturally competent and equitable ADRD care for this community. This study explores PCP perspectives to inform the development of accessible models that improve early diagnosis, preventive care, and quality of life for Latinx individuals with ADRD.

Methods

Qualitative interviews with 23 diverse PCPs across the USA (via videoconference or phone) were analyzed using thematic analysis. Snowball sampling and rigorous data reduction techniques ensured robust findings.

Results

Key themes emerged highlighting the interplay of organizational and policy factors: 1) Policy Constraints: Insurance eligibility and care options for those uninsured were foremost, with mandated language services facing access and quality challenges that affected the ability of clinicians to perform an accurate diagnosis. 2) Resource‐Dependent Care: Staffing and available resources dictated the type of care offered, leading to inconsistent protocols and options. Providers referred that work‐up was usually limited to referral to specialty care or ruling out other causes, and this was influenced by their level of training, time availability, and comfort. 3) Comprehensive assessments that include evaluation of their home and social environment, while recognized as crucial, were limited by appointment constraints and lack of follow‐up resources. 4) Family Involvement was critical in the diagnosis process, and some PCPs recognized the importance of educating families in the disease process and care needs.

Conclusion

Economic and organizational factors, including insurance, costs, staffing models, and resource navigation, shape PCPs' ability to deliver culturally competent and equitable ADRD care. Future interventions should address these barriers through: Training of PCPs in diagnostic procedures in Latinx communities, developing accessible service models and culturally appropriate diagnostic tools, and utilizing PCPs' trusted position to promote early diagnosis and preventive care.
Altered Effective Connectivity Patterns in Low‐Gamma Band for MCI Patients in a Motion Detection Task
Authors: Renli Alina Brighty , Sun Boxin , Gu Ming , Deng Jinxian , Kavcic Voyko , Li Tongtong , Giordani Bruno ,   Michigan Alzheimer's Disease Research Center
Published: January 2025

Background

Changes in effective connectivity, which represents the directed connectivity or information flow from one brain region to the other, have been proposed to underlie mild cognitive impairment (MCI) and Alzheimer’s disease (AD) pathology. The present study explores possible differences in brain effective connectivity between persons with normal cognition (NC) and patients with MCI.

Method

Our research focuses on task‐based EEG (64‐channel) acquired at Wayne State University, where participants were asked to perform a motion direction discrimination task. The current dataset includes 56 consensus‐diagnosed, community‐dwelling African Americans with subjective cognitive complaints (ages 60‐90 years, 28 NC and 28 MCI) recruited through the Wayne State Institute of Gerontology and Michigan Alzheimer’s Disease Research Center.

We evaluated the effective connectivity at different time periods of the motion‐detection task across all the possible EEG region pairs using causalized convergent cross‐mapping (cCCM) of the current source density. For each task trial, the successive time periods being examined included: (I) stimulus onset to Go/No‐Go indication, (II) Go (or No‐Go) indication to motion‐stop, and (III) the button‐press period.

Result

Our analysis indicated that MCI patients showed increased bidirectional effective connectivity in low‐gamma band (30‐48Hz) over MP (medial parietal)—Occ (occipital) and MP—MC (medial central) pairs in all the time periods during the motion task.

Conclusion

Altered effective connectivity measures in low‐gamma band may reflect compensatory brain activity among older individuals with MCI as they struggle to achieve comparable behavioral results to NC during the motion direction discrimination task. While effective connectivity may be decreased for MCI across certain region pairs (see Figures), a significant increase in effective connectivity in some other region pairs may be an indicator associated with AD and MCI pathology.

Funding: NSF‐2032709/Li; NIH‐1R21AG046637‐01A1/Kavcic; NIH‐1R01AG054484‐01A1/Kavcic; NIH‐P30AG072931/Paulson and NIH‐P30AG024824/Yung.
Association between long‐term Environmental Enrichment and Memory‐Related Functional Brain Activity in the DELCODE cohort
Authors: Hass Simon , Soch Joram , Kizilirmak Jasmin , Liebscher Maxie , Düzel Emrah , Fliessbach Klaus , Jessen Frank , Laske Christoph , Peters Oliver , Priller Josef , Roeske Sandra , Schneider Anja , Schuetze Hartmut , Spottke Annika , Teipel Stefan , Wagner Michael , Wiltfang Jens , Gloeckner Franka , Schott Björn H. , Wirth Miranka , Klimecki Olga M.
Published: January 2025

Background

Environmental factors account for a considerable percentage of dementia cases. Studies in animal models have shown that environmental enrichment (EE; i.e., stimuli‐rich housing conditions) has positive effects on brain structure, including the memory system. In humans, EE as measured by the engagement in a variety of leisure activities has been associated with better fornix structure and memory (Klimecki et al., 2023). We assessed whether long‐term EE (in terms of engagement in diverse leisure activities) is related to functional brain activity in the memory system of older adults.

Methods

We operationalized individual EE in 372 older participants aged between 60 and 87 years of the DZNE Longitudinal Study on Cognitive Impairment and Dementia (DELCODE) study. We used subscales of the Lifetime of Experiences Questionnaire (LEQ; Valenzuela & Sachdev, 2007) that capture the frequency of engagement in diverse leisure activities in young adulthood and middle life (13‐30 and 30‐65 years). Memory‐related brain activity was assessed using individual FADE‐SAME scores in a functional magnetic resonance imaging (fMRI) paradigm on visual memory encoding and recognition. The scores capture the similarity of older adults’ brain activity patterns with typical activations of younger adults’ (Soch et al., 2021). We performed multiple regression analyses between long‐term EE as independent variable and FADE‐SAME scores related to novelty processing and subsequent memory as dependent variables.

Result

Long‐term EE was significantly associated with novelty‐based SAME scores. More specifically, older participants with higher EE in early and middle life showed a higher similarity of functional brain activity patterns during novelty processing with the patterns seen in younger adults (see Figure 1). Exploratory subgroup analysis showed that this association was predominantly found in participants with Subjective Cognitive Decline (SCD, n = 199). No other significant findings were obtained.

Conclusion

Engagement in a variety of leisure activities during early and middle life is related to more “youth‐like” memory‐related brain activity patterns in older adults, including older individuals at increased risk of AD. Higher EE during early life might contribute to preservation or promotion of memory functions in later life.
Plasma metabolic profiles predict future dementia and dementia subtypes: a prospective analysis of 274,160 participants
Authors: He Xiao‐Yu , Qiang Yi‐Xuan , YOU JIA , Cheng Wei , Yu Jin‐Tai
Published: January 2025

Background

Blood‐based biomarkers for dementia are gaining attention due to their non‐invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all‐cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) and assessed their predictive potential.

Method

This study included 274,160 participants from the UK Biobank. Cox proportional hazard models were employed to investigate longitudinal associations between metabolites and dementia. The importance of these metabolites was quantified using machine learning algorithms, and a metabolic risk score (MetRS) was subsequently developed for each dementia type. We further investigated how MetRS stratified the risk of dementia onset and assessed its predictive performance, both alone and in combination with demographic and cognitive predictors.

Result

During a median follow‐up of 14.01 years, 5,274 participants developed dementia. Of the 249 metabolites examined, 143 were significantly associated with incident ACD, 130 with AD, and 140 with VaD. Among metabolites significantly associated with dementia, lipoprotein lipid concentrations, linoleic acid, sphingomyelin, glucose, and branched‐chain amino acids ranked top in importance. Individuals within the top tertile of MetRS faced a significantly greater risk of developing dementia than those in the lowest tertile. When MetRS was combined with demographic and cognitive predictors, the model yielded the area under the receiver operating characteristic curve (AUC) values of 0.857 for ACD, 0.861 for AD, and 0.873 for VaD.

Conclusion

We conducted the largest metabolome investigation of dementia to date, for the first time revealed the metabolite importance ranking, and highlighted the contribution of plasma metabolites for dementia prediction.
Exposure to perfluoroalkyl substances as a novel risk factor for cognitive impacts in older Asian Americans
Authors: Liu Shelley , Chen Yitong , Manz Katherine , Buckley Jessie , Parekh Ankit , Zhu Carolyn W. , Spat‐Lemus Jessica , Kukull Walter A. , Sano Mary , Li Clara
Published: January 2025

Background

Environmental pollutants, called perfluoroalkyl substances (PFAS) have been linked to adverse cardiometabolic outcomes, immune dysfunction and cancer risk, but their associations with adult cognition are unknown. Nearly everyone in the United States has detectable levels of PFAS in their blood, but our prior work found that Asian Americans have the highest exposure burden. As Asian Americans fastest growing segment of older adults, examination of relationships between serum PFAS concentrations and cognition in Asian Americans urgently needed. Here, our study examined those associations in older Asian Americans using the National Health and Nutrition Examination Survey (NHANES), and compared findings to a non‐Hispanic White sample.

Method

Our cross‐sectional study used 2011‐2014 (NHANES) data and included 57 non‐Hispanic Asian and 448 non‐Hispanic White participants who took the cognitive assessments in English, to minimize impact of assessment language on scores. Measures included the Animal Fluency test total score and word learning and recall modules from the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) (immediate recall and delayed recall scores).

We used linear regression to estimate impact on cognitive functioning measures per interquartile (IQR) increase in log PFOS concentrations adjusting for age, sex, education, BMI, fish consumption, and serum creatinine. To adjust for co‐pollutant confounding, we also adjusted for summed concentration of other six other PFASs. We stratified all analyses by race/ethnicity group.

Result

Our sample of Asian Americans had median age of 67 [IQR: 63, 74], and 41% were female. The non‐Hispanic White sample had median age of 72 [66, 80] and 54% were female. In Asian Americans, an IQR increase in log PFOS was associated with ‐4.42 (95% CI: ‐7.02, ‐1,82, p = 0.002) fewer words listed in the animal fluency test, ‐1.30 (95% CI: ‐2.43, ‐0.18, p = 0.025) words listed in the delayed recall, and ‐1.67 (95% CI: ‐3.68, 0.33, p = 0.098) fewer words listed in the immediate recall test (Table 2 and Figure 1). All associations were null for non‐Hispanic Whites.

Conclusion

Higher blood levels of perfluoroalkyl substances were associated with lower animal fluency scores and delayed recall scores in Asian Americans, but these associations were null for non‐Hispanic Whites.
Poorly controlled seizures are associated with severe neuropathological changes in dementia
Authors: Zawar Ifrah , Quigg Mark S , Manning Carol A , kapur jaideep
Published: January 2025

Background

Seizures maybe associated with worse neuropathology findings in people with dementia. However, the role of seizure control and how it may impact post‐mortem histopathology findings in people with dementia remains unexplored.

Method

We used the longitudinal, multicenter National Alzheimer Coordinating Center data from 9/2005 to 12/2021 to evaluate the association between seizure control and histopathological neurodegenerative changes in people with dementia. The differences between baseline demographics, cognition, mortality and neuropathology findings were investigation among three groups: 1) Recurrent seizures (over the preceding 12 months), 2) Remote seizures (history of seizures but no seizures over the preceding 12 months) and 3) No history of seizures (controls). Pearson’s Chi‐squared test, fisher’s exact test and Kruskal‐Wallis Rank sum tests were utilized for analysis as deemed appropriate.

Result

Of 10,474 NACC participants who died, mortality was higher (p<0.001) among recurrent seizure (N=407, 56%) patients compared to remote (N=221, 35%) seizures and controls (N=9846,34%). Among 6085 who underwent autopsy, 294 had recurrent seizures, 151 had remote seizures and 5640 had no seizures. Recurrent seizure patients were younger than controls at death (76 vs 82 years, p<0.001). There were no group differences in education, sex, race and ethnicity. However, recurrent seizure patients had worse cognition compared to other groups. Lobar atrophy, vascular pathology, atherosclerosis of circle of willis and substantia nigra hypopigmentation were comparable among the 3 groups. However, recurrent seizure patients had more cerebral cortex atrophy (p<0.001), hippocampal atrophy (p=0.016) and locus ceruleus hypopigmentation (p=0.011). While Lewy body pathology was similarly prevalent among the groups, frontotemporal degeneration with tau pathology was less prevalent (p=0.013) among the recurrent seizures compared to other groups. Recurrent seizure patients had evidence of more severe Alzheimer’s disease pathology (AD) including thal phase for amyloid, Braak stage for neurofibrillary degeneration and density of neocortical neuritic plaque (p<0.001).

Conclusion

Our findings suggest that recurrent seizures compared to remote seizures prior to death are associated with postmortem evidence of more severe AD pathology and cortical and hippocampal atrophy. These findings emphasize the need for more aggressive seizure control to mitigate the potential impact of seizures on neurodegeneration.
New high throughput fully automated plasma GFAP immunoassay
Authors: Szabo Miklos , Salvati Mike , Schlichtmann Ben , Patzlaff Jason , Unruh Dusten , Curtis Kara , Mediger Laura , Nichkova‐Doseva Mikaela
Published: January 2025

Background

The analytical performance characteristics for the plasma Glial Fibrillary Acidic Protein (GFAP) immunoassay currently under development on Beckman Coulter, Inc. Access2™ and DxI9000™ analyzers is described. Blood GFAP levels may be indicative of the extent of neurologic injury in diseases such as TBI and stroke and maybe used as a marker of disease progression in other diseases such as multiple sclerosis. Plasma GFAP outperforms its CSF counterpart in detecting AD pathology and correlation to the clinical stage of the disease

Method

The prototype GFAP assay is a one‐step sandwich assay utilizing an anti‐GFAP mouse monoclonal (MAb) antibody/alkaline phosphatase conjugate and paramagnetic particles coated with a complementary anti‐GFAP mouse MAb. Sample and reactants are incubated, washed, then a chemiluminescent substrate is added. The light that is generated is directly proportional to the GFAP concentration in the sample. The assay time to first result is ∼30 minutes. 43 EDTA plasma samples, consisting of 19 Alzheimer’s Disease (AD) patient samples and 24 age‐matched healthy normal samples, were evaluated. A method comparison was performed between Access2™ and DxI9000™ platforms.

Result

The prototype GFAP assay has a targeted analytical measuring range of 1.0 pg/ml to approximately 700.0 pg/ml (capable of measuring analyte up to 10,000 pg/ml). 100% of normal samples were quantified (90% measuring below 20.0 pg/ml), with low dose variability (<4.0% coefficient of variation). A comparison of the prototype GFAP assay on DxI9000™ against Access2™ gave a Passing‐Bablok slope of 0.94 (R=0.992) and an intercept of 0.37 pg/ml. Concordance analysis shows excellent agreement between the Access2™ and DxI9000™ assays. The dose ratio of the median of AD over the median of normal samples for Access2™ and DxI9000™ is 2.31 and 2.41, respectively, with AD patient median dose values of 14.3 pg/ml and 14.6 pg/mL, respectively, and normal sample median dose values of 6.2 pg/ml and 6.0 pg/mL, respectively.

Conclusion

The prototype GFAP assay provides fast, highly sensitive and precise results in an automated immunoassay on the Beckman Coulter Access2™ and DxI9000™ platforms. The prototype plasma GFAP assay could be used to both diagnose and monitor various neurodegenerative diseases such as AD.
Mindfulness‐Based Cognitive Defusion Training for Perceived Stress in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Study
Authors: Ren Yinxia , Shi Lulu , Ge Chenxi , Gu An , Wang Lina
Published: January 2025

Background

Recognizing perceived stress as a modifiable cognitive risk factor, mindfulness‐based programs emerge as promising for stress mitigation in older adults with Mild cognitive impairment (MCI). However, existing research, primarily observational and focused on chronic patients and caregivers, necessitates developing and evaluating MCI‐specific mindfulness interventions.

Design

A two‐arm and assessor‐blinded randomized controlled trial.

Settings and participants

Community‐dwelling older adults with MCI.

Method

Participants (N = 102) were randomly allocated to one of the two arms: (1) a M‐bCDT program (weekly 60‐minute supervised sessions for 8 weeks, followed by 12 weeks of unsupervised practice) or (2) health promotion classes alone, with M‐bCDT program after the follow‐up assessment. Measures of perceived stress levels, cognitive function, and mindfulness awareness levels were collected at baseline (T0), 8‐week (T1), and 20‐week (T2). Intervention effects were assessed both at a group level (Generalized Estimating Equation, GEE) and at an individual level (Reliable Change Index, RCI).

Result

In the intervention group, the M‐bCDT program demonstrated significant interaction effects compared to the waitlist control group. GEE analysis revealed showed statistically significant effects on perceived stress at both measured intervals (βT1 = ‐3.686, P<0.001; βT2 = ‐7.608, P<0.001). In cognitive functioning, significant cognitive improvements were noted in the Finger Tapping test (βT1 = 1.020, P = 0.026; βT2 = 3.000, P<0.001), Purdue Pegboard Test Assembly and Bimanual Tasks (βT1 = 0.549/0.784, P = 0.048/0.013; βT2 = 1.510/2.059, P<0.001), Auditory Verbal Learning Test (AVLT‐immediate/delayed recall: βT1 = 1.098/0.667, P<0.001/0.038; βT2 = 2.176/1.373, P<0.001), and Montreal Cognitive Assessment scores, mindfulness awareness levels in observation and non‐judgment dimension improved significantly over time. RCIs indicated improvements in the intervention group of 1.96% in perceived stress level, 70.59% and 60.78% in AVLT‐immediate/delayed recall after 8 weeks, which further increased to 31.37%, 90.20%, and 78.43% after 20 weeks.

Conclusion

The M‐bCDT program effectively reduced the perceived stress levels in older adults with MCI, facilitating the improvements in cognitive function and mindfulness awareness levels, with sustained benefits for three months. It offers a standardized approach for community healthcare providers in MCI cognitive management.

Trial registration

The trial was registered at Chinese Clinical Trials Registry on 05/18/2020 (www.chictr.org.cn; Number Registry: ChiCTR2000033013).

Funding

National Natural Science Foundation of China (NO. 72174061; NO. 71704053), China Scholarship Council Foundation (NO. 202308330251).
Feasibility of Training Family Caregivers of People Living with Dementia Online to Deliver Life Review Depression Intervention at Home
Authors: Miyawaki Christina E. , Bouldin Erin D. , McClellan Angela
Published: January 2025

Background

Due to the high prevalence of depressive symptoms and dementia in older Americans (≥65 years), we trained unpaid family caregivers in an evidence‐based life review depression intervention virtually via Zoom and produced positive outcomes. The objective of this study was to examine the feasibility of training caregivers via online video and delivering the intervention at home.

Method

We recruited caregiver‐care recipient dyads nationwide during the COVID‐19 pandemic (N = 20 dyads). A mixed‐methods design was used to examine the results quantitatively and supported the findings with qualitative interviews with caregivers. We used fidelity scores as a measure of caregivers’ feasibility to follow the intervention protocol and conduct the life reviews. We collected the pre‐ and post‐intervention measures on care recipients’ depression as the primary outcome, and life satisfaction, caregivers’ caregiving burden, rewards of caregiving, and dyads’ relationship quality as secondary outcomes, and analyzed them using paired t‐tests.

Result

Caregivers were on average 64 years old, White (65%), and female (90%). Many were married (65%), college‐educated (70%), working or retired (40% each), and in good‐excellent health (100%). Their care recipients were 80 years old (mean), and White (70%). Gender and their health conditions were equally divided into male and female (50% each), and in poor‐fair and good‐excellent health (50% each). The online‐trained caregivers’ average fidelity check‐in score was 15.86±0.268 (out of 16), which was a significant improvement from that of Zoom‐trained caregivers (14.83±0.776, p<0.001) indicating excellent adherence to the intervention protocol. The C‐PLR intervention significantly positively impacted care recipients’ depressive symptoms (p = 0.034), as well as caregivers’ rewards of caregiving (p = 0.019), especially care recipients who lived alone (p = 0.024). Caregivers’ post‐intervention qualitative interviews aligned with the quantitative results supporting that online‐trained caregivers could deliver the intervention by the protocol without adding caregiver burden.

Conclusion

The outcomes of the study showed that family caregivers could learn life review skills through online videos and perform life reviews closely adhering to the study protocol. This study demonstrated that the Caregiver‐Provided Life Review, an innovative, cost‐effective intervention with a flexible delivery schedule could make a positive impact on both caregivers’ and care recipients’ mental health.
Cultural adaptation of the Savvy Caregiver program with the Native Hawaiian community
Authors: Jackson Alexandra , Dillard Adrienne , Kekauoha B. Puni , Austin Mahealani , Kia'i Lee Errol , Balaz Poki'i , Dutro Natlie , Okamoto Scott , Hepburn Kenneth , Lewis Jordan P. , O'Sullivan Kelly , Mayeda Paige , Dutro Angeliyah Kahoku , Weaver Raven
Published: January 2025

Background

To promote caregiver health and reduce burden, the Savvy Caregiver Program (SCP), an evidence‐based caregiving intervention, was adapted with a Native Hawaiian (NH) community in Hawaiʻi. The adaptation process occurred prior to pilot testing in two phases: 1) the preliminary adaptation by a community action board (CAB) and mentorship team and 2) pre‐pilot testing and expert validation with NH adults. The preliminary adaptation, titled ʻAuamo Kuleana O Nā Maʻi Poina (ʻAuamo Kuleana), aimed to include Hawaiian values, language, proverbs, and culturally relevant examples while maintaining the core components of the program. The CAB also created new videos with cultural foods, mirroring the existing training videos. To continue refining the adapted program prior to pilot testing, we pre‐piloted the curriculum and invited participants to describe their experiences and provide feedback.

Method

Individuals who participated in the 7‐week pre‐pilot of ʻAuamo Kuleana (n = 6) were asked to complete a focus group or interview to share their experiences and provide feedback. The CAB was invited to analyze the qualitative data using thematic analysis.

Result

Five pre‐pilot participants attended a focus group or interview. Only one participant was actively providing care, the other participants were interested in proactive training to support their community. This was a common theme: caring as a community. Participants shared positive feedback about the program; most participants attended all sessions and read the caregiver manual. All participants preferred to meet in‐person and appreciated the revised curriculum. Two suggestions emerged: include all family members in the program to be in alignment as a ʻohana (family) in providing care; and add information about planning for their own care.

Conclusion

There were high rates of satisfaction and engagement and the pilot test of ʻAuamo Kuleana proceeded without additional changes. The suggested changes from the pre‐pilot required modifications to program core components and were not incorporated at this stage. However, it may be important to consider how to incorporate cultural aspects of caring, like participants' interest in proactively learning about dementia and caregiving, caring as a community, and family‐centered caregiving (rather than dyadic caregiving), in future caregiving interventions co‐created with the NH community.
Prevalence of Cerebral Small Vessel Lesions in Mild Cognitive Impairment and Mild Alzheimer’s Disease Patients in Memory Clinic
Authors: Smitasiri Thachamai , Likitjaroen Yuttachai
Published: January 2025

Background

Alzheimer's disease(AD) raises global concern with its impact on daily living. Anti‐amyloid monoclonal antibodies (mAb) serving as specific treatments used in mild cognitive impairment(MCI) and mild dementia due to AD. Severe cerebral small vessel disease(SVD) lesions such as microbleeds and white matter hyperintensities are listed as exclusions according to the recommendation for mAb treatment. In Thailand, there is no prevalence study of SVD lesions specifically in these patient grpups. The findings will provide important information for considering cost‐effectiveness of anti‐amyloid therapy, being expected to become treatment option for Thai AD patients.

Method

The cross‐sectional study was carried out at King Chulalongkorn Memorial Hospital Memory Clinic. Amnestic MCI and mild AD patients were diagnosed by clinical criteria, cognitive tests and brain MRI. Serious medical conditions and incomplete MRI were excluded. Visual rating scales were used to evaluate SVD and brain atrophy lesions (microbleeds, Fazekas score, lacunes, MTA and GCA scores). Baseline characteristics data and cognitive tests were accessed from medical records. Simple and amended SVD scores were used to determine SVD severity and analyzed correlation with cognitive tests.

Result

In the study involving 102 patients, 73.5% had MCI, and 26.5% had mild AD, with average age at diagnosis of 75.0±8.0 years. Microbleeds were present in 50% of patients, with only 17.6% had ³4 lesions. Twenty individuals (19.6%) had either ³4 microbleed lesions or Fazekas score of 3. There was no evidence of superficial siderosis or stroke involving large vessel territory. Those without microbleeds had higher TMSE score (25.4vs23.5;p=0.009). MTA score were associated with lower TMSE and MoCA scores (26.4vs22.7;p<0.001 and 22.1vs19.2;p=0.001, respectively). Weak negative correlation between simple & amended SVD scores and TMSE scores were showed (r=‐0.371 and ‐0.384, respectively;p<0.001), along with moderate negative correlation between MTA score and both TMSE & MoCA score (r=‐0.631 and ‐0.443, respectively;p<0.001).

Conclusion

With MCI and mild AD, 19.6% of the samples fell within the exclusion criteria for anti‐amyloid therapy, in part of cerebrovascular imaging lesions. The results can be used to consider role of anti‐amyloid therapy in Thailand in the future.
Cognitive Reserve as a Predictor of Age of Onset and Cognitive Decline in Patients with Alzheimer’s Disease
Authors: Marmor Anat , Vakil Eli , Merhavi Shlomzion Kahana , Meiner Zeev
Published: January 2025

Background

The cognitive reserve (CR) theory seeks to explain the mismatch often reported between brain damage and its clinical expression. Unlike most previous studies that focused on individuals with memory deterioration before the diagnosis of Alzheimer’s disease (AD), the present study examined the late stages of the disease. The study sought to confirm the hypothesis that patients with higher CR are diagnosed later and decline faster than those with lower CR because their brain pathology is more severe.

Method

This is a retrospective study conducted at a memory clinic and included 642 (361 female) individuals above the age of 65 diagnosed with AD. Average age was 77.01 (range = 65‐97). Cognitive decline was evaluated using the Mini Mental State Examination (MMSE).

Result

In the entire sample, no significant correlation was found between the age of diagnosis and CR. Therefore, the sample was divided into two groups, according to years of education: (a) patients with nine years of high education or more (n = 442, with average years of education 13.93, SD = 3.00) and (b) patients with eight years of education or less (n = 141, with average years of education 5.21, SD = 3.08). Our results show that only in the group of patients with higher education, education level was significantly associated with delayed age of diagnosis. As predicted, more years of education were associated with steeper cognitive decline in both groups.

Conclusion

The study examined the less studied group of individuals at late stages of AD. The study shows that the effect of education on the age of diagnosis is not linear and it is valid for those with a higher but not necessarily for those with lower education. In patients with higher education, higher CR resulted in delayed age of diagnosis but also faster deterioration; in the lower education group, the resilience factor that leads to later diagnosis is not present. The implications of the study include diagnostic and therapeutic guidelines that match the different characteristics of each group of patients.
The effect of herpes zoster vaccination on the occurrence of deaths due to dementia in England and Wales
Authors: Michalik Felix , Xie Min , Eyting Markus , Hess Simon , Chung Seunghun , Geldsetzer Pascal
Published: January 2025

Background

Using a unique natural randomization, we have recently provided evidence from Welsh electronic health record data that herpes zoster (HZ) vaccination caused a reduction in new dementia diagnoses over a seven‐year period. This study aimed to determine whether eligibility for HZ vaccination also caused a reduction in deaths due to dementia in England and Wales over a nine‐year follow‐up period.

Methods

Adults who had their 80th birthday shortly before September 1 2013 were ineligible for free HZ vaccination and remained ineligible for life, whereas those who had their 80th birthday shortly after September 1 2013 (i.e., born on or after September 2 1933) were eligible for one year. This date‐of‐birth threshold generated birth cohorts who are likely exchangeable in observed and unobserved characteristics except for a small difference in age and a large difference in HZ vaccination uptake. We used country‐wide data from death certificates in England and Wales on underlying causes of death from September 1 2004 to August 31 2022 by ICD‐10 code and month of birth. Our analysis compared the percentage of the population with a death due to dementia among the month‐of‐birth cohorts around the September 2 1933 eligibility threshold using a regression discontinuity design.

Results

The study population included 5,077,426 adults born between September 1 1925 and August 31 1941 who were alive at the start of the HZ vaccination program. We estimated that over a nine‐year follow‐up period, eligibility for HZ vaccination reduced the percentage of the population with a death due to dementia by 0.38 (95% CI: 0.08 to 0.68, p = 0.012) percentage points, corresponding to a relative reduction of 4.8%. As in our prior analysis, this effect was stronger among women (‐0.62 [95% CI: ‐1.06 to ‐0.19] percentage points, p = 0.004) than among men (‐0.11 [95% CI: ‐0.51 to 0.28] percentage points, p = 0.574).

Conclusions

Our findings indicate that HZ vaccination reduced cognitive decline at a fairly advanced stage of the dementia disease process because most individuals whose underlying cause of death was dementia during our nine‐year follow‐up period were likely already living with dementia at the start of the HZ vaccination program.
White matter microstructure and cognition in the Alzheimer’s Disease Connectome Project (ADCP)
Authors: Roberts John Weston , Adluru Nagesh , Nair Veena A. , Adluru Anusha , Nencka Andrew S , Li Shi‐Jiang , Davidson Richard J , Okonkwo Ozioma C , Alexander Andrew L , Bendlin Barbara B. , Prabhakaran Vivek
Published: January 2025

Background

Alzheimer’s disease (AD) has been mainly thought of as a disease involving gray matter changes. However, despite known correlations between white matter integrity and cognition, less is known about how disruptions to white matter during the development of AD underpin cognitive impairment. This study tests the associations between disruptions to white matter along the AD clinical continuum (cognitive unimpaired (CU): cognitive impaired (CI) – Mild Cognitive Impairment (MCI) and AD) and cognition using diffusion tensor imaging (DTI) and multi‐tissue neurite and orientation dispersion and density imaging (mtNODDI) models of the multi‐shell connectome diffusion MRI (ms‐dMRI) data from the Alzheimer’s Disease Connectome Project (ADCP).

Method

Multi‐shell connectome diffusion MRI data from 80 participants (55 CU (32 F, mean age 66.7 +/‐ 6.6; 25 CI (8 F, mean age 73.6 +/‐ 7.3)) in the ADCP were pre‐processed using DESIGNER processing guidelines. Cognition was assessed using the Cognition Total Composite score from the NIH toolbox. Permutation testing was performed using threshold free cluster enhancement and family wise error correction (FWE) and 10,000 permutations. Relationships between cognitive impairment and white matter integrity were deemed statistically significant for FWE corrected p < 0.05. All analyses controlled for age and sex.

Result

Our analysis revealed a significant interaction between clinical status and cognitive test outcomes on the mtODI (multi‐tissue orientation dispersion index) metric, with higher mtODI levels indicating increased neurodegeneration. CU individuals exhibited higher cognitive performance with lower mtODI levels in cerebellar and brainstem regions, whereas CI individuals showed consistently higher mtODI levels in these regions and lower cognitive performance (Figure 1). Moreover, CI individuals presented with lower overall cognitive test scores compared to their CU counterparts. Analysis of clusters uncorrected for multiple comparisons revealed trend‐level differences in frontal and temporal regions (Figures 2‐3).

Conclusion

Results demonstrate that CI individuals who perform worse than CU individuals on cognitive tests also have higher levels of neurodegeneration than CU individuals. Further research is needed to replicate and extend these findings to other tests of cognitive ability, and to help better understand the potential links between cognitive decline in AD with white matter integrity of cerebellar and brainstem regions.
APOE‐ε4 is associated with poor sleep and structural differences of the hypothalamus in the PREVENT‐Dementia and ALFA cohort studies
Authors: Laurell Axel AS , Mak Elijah , Underwood Benjamin R , Dauvilliers Yves , Ritchie Craig W , Koychev Ivan , Lawlor Brian A , Naci Lorina , Malhotra Paresh , Grau‐Rivera Oriol , Gispert Juan Domingo , O'Brien John T
Published: January 2025

Background

Sleep disturbances have been identified as a risk factor for developing dementia. The hypothalamus is involved in sleep regulation and may be affected early by neurodegeneration. Our aim was to investigate the relationship between subjective sleep and hypothalamic structure in adults at higher risk of developing dementia.

Method

We analysed baseline data from PREVENT‐Dementia (n=700) and ALFA (n=1478), which are prospective cohort studies of cognitively healthy, middle‐aged participants, who were stratified by apolipoprotein E (APOE) genotype for their risk of dementia. Subjective sleep data was collected using the Pittsburgh Sleep Quality Index (PSQI), including the following components: sleep quality, latency, duration and efficiency. The volumes of five hypothalamic subunits were extracted by automatic segmentation of T1‐weighted 3T MRI images using Freesurfer (version 7.2.0). Combat harmonisation was used to account for using multiple MRI scanners. The data was analysed in R Studio using robust linear and logistic regression, correcting for age, sex, depression, total intracranial volume and multiple comparisons.

Result

The ALFA cohort was significantly older than PREVENT‐Dementia (mean 60 versus 51 years, p<0.001). In the combined datasets, APOE‐ε4 homozygotes had a larger anterior‐superior hypothalamus compared to heterozygotes (p=0.02) and non‐carriers (p=0.02). Furthermore, APOE genotype moderated the association between age and volume of the anterior‐superior hypothalamus (p=0.02), such that APOE‐ε4 carriers had smaller volume with age (homozygotes: m=‐0.19, p=0.14; heterozygotes: m=‐0.17, p<0.01) compared with non‐carriers (m=‐0.10, p<0.01). Long sleep latency was associated with a smaller anterior‐inferior hypothalamus (p=0.05). Sleep latency also moderated the relationship between age and the volume of the anterior‐inferior hypothalamus (p=0.04). While subjects with short sleep latency showed a positive correlation between larger volume and age (m=0.06, p=0.07), there were no correlation with age in those with long sleep latency (m=‐0.01, p=0.91). In the ALFA cohort only, APOE‐ε4 carriers had longer sleep latency than non‐carriers (p=0.02).

Conclusion

APOE‐ε4 carriers have a larger anterior‐superior hypothalamus and worse sleep, which may be due to early pathological processes. Our findings underscore the role of the hypothalamus in sleep homeostasis and suggest that involvement of subcortical structures may relate to early symptoms in individuals at risk of dementia.
Graphical indices of brain aging
Authors: Furlano Carmensita , Gareri Pietro
Published: January 2025

Background

Writing is a cortical function studied by the human science of Graphology, which allows the personal knowledge of the subject, and psychophysical conditions, both in healthy older people and in those affected by dementia. Graphologists and geriatricians can successfully cooperate with this.

Method

Five volunteers aged between 60 and 80 years old (3 women and 2 men) were enrolled after signing an informed consent. Each participant underwent multidimensional geriatric evaluation, medical examination, and instrumental exams (Table 1). Each person was asked to write the sentence “I breathe the sweet scent of flowers”, on which Graphological Analysis (in blind) was conducted, based on the evaluation of some variables. Graphology is set up through the neurophysiology of four writing movements: Flexion and Abduction determine the ‘cup’, the Extension prepares the attack of the next letter and its implementation, the Adduction intervenes in the eyelets and in all the gestures of return backwards.

Result

In 4 out of 5 participants, the graphological indices of brain aging were present: slow and heavy writing, a broken, laid or slow rhythm, an uncertain and irregular direction, small superfluous traces, shake, angular and discontinuous movements, the presence of juxtapositions, tremors, disproportions, inequalities in size and deformation of individual letters, tightening of the letters, or high magnification.

Conclusion

It is necessary to promote the presence of the Graphologist in the Healthcare fields, by creating local Geriatric Graphology Centers, in collaboration with multidisciplinary teams, where prevention, diagnosis, rehabilitation/therapeutic treatment, study and research activities can be carried out.
Effect of kidney function on plasma pTau217 concentrations using different pTau217 assays
Authors: Algeciras‐Schimnich Alicia
Published: January 2025

Background

Chronic kidney disease (CKD) has been associated with increased plasma phosphorylated Tau217 (pTau217) concentrations, potentially confounding its utility in the evaluation of Alzheimer's disease (AD). We assessed the association of estimated glomerular filtration rate (eGFR) with plasma pTau217 concentrations measured by various assays.

Method

We included 195 participants from the Mayo Clinic Study of Aging or the Alzheimer’s Disease Research Center with diagnoses of cognitively unimpaired (n=114), mild cognitive impairment (n=70), and AD dementia (n=11). Amyloid‐PET was performed with Pittsburgh 11C‐Compound B; abnormal amyloid (A+) was defined as SUVR ≥1.52 (Centiloid ≥25). eGFR was determined based on serum creatinine concentrations. pTau217 was quantified using ALZpath Simoa pTau217 immunoassay, Fujirebio Lumipulse G pTau217(N‐Terminal) immunoassay, and a pTau217 mass spectrometry (MS) assay (C2N Diagnostics). Additionally, a pTau217 ratio (pTau217 to non‐phosphorylated [npTau217]) was calculated using the MS assay. Linear regression was used to assess associations of continuous eGFR with plasma pTau217 and amyloid PET. Differences in mean plasma concentrations between eGFR groups by amyloid PET status were evaluated with one‐way ANOVA tests and associated confidence intervals for each sample mean.

Result

Median pTau217 concentrations in the A+ and A‐ groups were higher in individuals with eGFR <60 mL/min/1.73 m2 compared to those with eGFR ≥60 in all assays except for the A+ group when using the pTau217/npTau217 ratio. A 10‐unit worsening of eGFR was associated with higher pTau217 mean concentrations as follows: 24% (95% CI, 13‐36%) for C2N pTau217, 16% (9‐24%) for ALZpath pTau217, and 12% (5‐20%) for Lumipulse pTau217. eGFR was not significantly associated with the pTau217/npTau217 ratio or amyloid‐PET.

Conclusion

CKD was associated with increased pTau217 concentrations when measuring pTau217 but not when using the pTau217 ratio. Additional research is needed to better understand the confounding effects of CKD in the clinical interpretation of plasma pTau217 assays.