bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal biomarkers for predicting Alzheimer’s disease and Frontotemporal dementia: A prospective cohort study of 30573 participants
Authors: Wang Ruihan
Published: January 2025

Background

Alzheimer’s disease (AD) and Frontotemporal dementia (FTD) are the two most common causes of early‐onset dementia. Differentiating between AD and FTD can be challenging due to overlapping cognitive and behavioral manifestations. However, evidence on non‐invasive and early‐stage biomarkers for differentiating AD and FTD is still limited. Optical coherence tomography (OCT), as a non‐invasive retinal imaging technique, has provided enhanced access to detailed retinal neuronal structure. Our aim was to identify retinal biomarkers for predicting AD and FTD in non‐demented population and explore underlying brain structural mechanism.

Method

We involved a total of 30573 UK Biobank participants without dementia, ocular disorders, and diabetes who underwent baseline retinal OCT imaging. Cox proportional hazard models were used to estimate the associations of macular OCT measurements with the risk of AD and FTD, adjusted for multiple confounding factors. Mediation models were applied to explore the underlying mechanisms driven by brain structures in subgroup participants with MRI scans.

Result

The mean age at recruitment was 55.27, and 46.10% of the participants were male. During a mean follow‐up of 9.15 ± 2.59 years, 148 AD and 8 FTD patients were identified. Greater thickness of ganglion cell‐inner plexiform layer (GC‐IPL) was associated with reduced risk of AD (HR, 0.968; 95% CI, 0.938–0.999; p=0.044), while thicker retinal pigment epithelial (RPE) at inner superior subfield was associated with lower risks of FTD (HR, 0.710; 95% CI, 0.534–0.943; p=0.018). Decreased cortical (mainly including regions in occipital, temporal, and parietal cortices) and subcortical (thalamus and hippocampus) grey matter volume, and white matter integrity mediated the effects of GC‐IPL thickness on AD risk.

Conclusion

Our findings provides evidence regarding the longitudinal association between macular OCT measurements and dementia. Thinning of the inner retinal layer is linked to a higher risk of AD, while thinning of the outer retinal layer is associated with an increased risk of FTD. Brain structures related to visual pathways mainly mediate the association between GC‐IPL and AD.
Blood‐based glial reactivity modulates cerebral amyloid and tau deposition in Alzheimer's disease
Authors: Lan Guoyu , Li Anqi , Yang Jie , Zhang Laihong , Fang Lili , Zhu Yalin , He Zhengbo , Zhou Xin , Liu Lin , Sun Pan , Cai Yue , Guo Tengfei
Published: January 2025

Background

Plasma biomarkers of Alzheimer’s disease (AD)‐related pathological changes are considered as proxies of their changes in the brain. Recent cohort studies reported very early changes in plasma astrocytic marker glial fibrillary acidic protein (GFAP) in the AD spectrum, which is relative to the onset of neuropathology. Little is known about the association between plasma soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and primary AD pathology. This study explored how GFAP and sTREM2 in plasma influence cortical β‐amyloid (Aβ) and tau deposition.

Method

We measured the concentrations of plasma biomarkers by the Simoa or MSD platforms in a total of 285 individuals from the Greater‐Bay‐Area Healthy Aging Brain Study (GHABS) cohort, a large community‐based cohort study of older adults from China. All of them underwent Aβ PET imaging ([18F]‐D3FSP or [18F]‐florbetapir), and 104 individuals were additionally scanned for tau PET imaging. We investigated the modification effect of plasma glial biomarkers (GFAP and sTREM2) on Aβ PET and tau PET using generalized linear models, controlling for age, sex, and diagnosis.

Result

Plasma GFAP but not sTREM2 interacted with Aβ42/Aβ40 and p‐Tau181 (Table 1), where higher GFAP levels were associated with steeper relations of lower Aβ42/Aβ40 and higher p‐Tau181 with elevated Aβ PET. Regarding tau PET, we found that higher plasma GFAP levels enhanced the association between plasma p‐Tau181 and tau PET. In contrast, higher plasma sTREM2 levels attenuated the associations of lower Aβ42/Aβ40 and higher p‐Tau181 with tau PET elevations. Congruent results were obtained when we used Aβ PET as the interaction term in the models. Furthermore, higher plasma sTREM2 levels also mitigated the association between plasma GFAP and tau PET but did not influence Aβ PET (Figure 1). At the voxel level, the association between plasma GFAP and tau PET was diminished and limited in individuals with above‐median sTREM2 levels versus individuals with below‐median sTREM2 levels.

Conclusion

This study provides novel insights into the link between plasma glial biomarkers and cortical deposition of Aβ and tau aggregates, where plasma GFAP is linked to augmented Aβ and tau pathology, whereas plasma sTREM2 is linked to attenuated tau accumulation.
Setting a Baseline for Normal Cognitive Aging with Lexical Concreteness – A Corpus Linguistic Approach
Authors: Han Kunmei
Published: January 2025

Background

Identifying language variation in healthy aging speakers is important for understanding normal cognitive aging. Setting a baseline of normal aging languages in the first place is necessary for the evaluation of language performances of old adults. Lexical concreteness, a well‐studied psycholinguistic parameter, has been used to detect semantic memory‐related deficits. For example, people with semantic dementia were found to display reduced lexical concreteness (Breedin et al., 1994). Healthy old adults, however, are less studied in terms of the concreteness pattern in their speech. This study examines lexical concreteness of free speech samples of normal aging speakers age between 60 – 80 in Singapore.

Method

We collected about 15‐min free speech from 243 English‐speaking, cognitively healthy Singaporeans (133 women, 110 men) age above 60 years old. Demographic variables (age, gender, education, and number of languages spoken) were uncorrelated with each other. Speeches were transcribed by native Singapore English speakers and tagged with part‐of‐speech (PoS) information. We calculated global lexical features including speech rate (in minutes), lexical diversity (Moving‐Average Type‐Token Ratio), and PoS distribution (count per 100 tokens). Then we calculated concreteness (Brysbaert et al., 2014) of major content words for every individual. The relation between age and lexical measures was examined with Spearman’s correlation test.

Result

Results of the statistical analysis show that healthy old adults speak slower (𝜌= ‐0.14, p= .03) with more concrete nouns (𝜌= 0.14, p= .03) and adjectives (𝜌= 0.18, p< .05) than younger speakers. PoS distribution and verb concreteness (all p> .05) remain stable in the aging process.

Conclusion

Our speech sample revealed a general trend of elderly speech – reduced speech rates and increased lexical concreteness. The significant positive association between age and lexical concreteness in free speeches of health old adults was found for the first time, providing corroborative evidence for the link between concreteness and semantic memory. We also found a dissociation between nouns and verbs, consistent with neuropsychological literatures that nouns and verbs are encoded in different areas of the brain (Vigliocco et al., 2011). In sum, measuring lexical concreteness in natural speech data can provide circumstantial evidence for evaluating cognitive aging.
Serum brain‐derived neurotrophic factor and progression to MCI in cognitively normal older adults
Authors: Kim Kyungtae , Byun Min Soo , Yi Dahyun , Jung Joon Hyung , Sohn Bo Kyung , Jung Gijung , Ahn Hyejin , Lee Jun‐Young , Lee Yun‐Sang , Kim Yu Kyeong , Lee Dong Young
Published: January 2025

Background

Brain derived neurotropic factor (BDNF) has been associated with improved neuronal survival and synaptic plasticity and long‐term memory. Some human studies also reported the relationship between lower blood BDNF levels and poorer memory function and dementia. A prior longitudinal study also demonstrated higher serum BDNF levels were associated with lower risk of overall dementia and Alzheimer’s disease (AD) dementia. However, it remains uncertain whether reduced serum BDNF levels precede the onset of mild cognitive impairment (MCI), which is known as pre‐dementia stage. This study aimed to examine whether higher serum BDNF in cognitively normal (CN) older adults is related to less common progression to MCI and to identify potential moderators of this relationship.

Method

A total of 278 CN older adults between 55 and 90 years of age were enrolled. All participants underwent comprehensive clinical assessments, serum BDNF level measurement, and multimodal brain imaging including Pittsburgh compound B (PIB)‐positron emission tomography (PET) at baseline, and followed up for up to 4 years. Serum BDNF levels were divided into two categories by median value of serum BDNF level: < 21448.5 pg/mL (low BDNF), and > 21448.5 pg/mL (high BDNF). Cox model was used to analyze the relationship between baseline BDNF levels and the risk for MCI progression controlling for potential confounders. We also ran sensitivity analyses stratified by sex, age, education, apolipoprotein E ε4 (APOE4) positivity, and amyloid PET positivity.

Result

During follow‐up, 24 participants developed MCI. Controlling for age, sex, education and APOE4 positivity, low BDNF group had significantly more frequent progression to MCI than high BDNF group (hazard ratio for MCI, 2.98; 95% CI, 1.17‐7.56; p=0.02) and these association persisted even after controlling for amyloid PET positivity and vascular risk factor score as additional covariates (hazard ratio, 2.98; 95% CI, 1.17‐7.55; p=0.02). Sensitivity analyses revealed that the associations were apparent only among women, participants aged younger than 75 years, those without college degrees, and amyloid negative participants (Table).

Conclusion

Higher serum BDNF levels may protect against future occurrence of MCI in cognitively healthy older adults. Such influence appears more prominent in women and younger, less educated, or amyloid PET negative individuals.
Psychometric evaluation of the Chinese modified perceived neighborhood cohesion scale in older adults at high risk of cognitive impairment
Authors: Chiu Yi‐Chen , Lin Mei‐Hsuan , Hsu Pei‐Chen , Hsu Wen‐Chuin , Chen Yi‐Chun
Published: January 2025

Background

The global increase in dementia cases underscores the need for community‐based services, particularly for older adults who spend significant time in their neighborhoods. This context profoundly influences cognitive function and quality of life, especially in those at high risk of cognitive impairment. Despite its importance, neighborhood cohesion has not been extensively studied in this group. This study aimed to assess the reliability and validity of the Chinese Modified Perceived Neighborhood Cohesion Scale (CMPNCS) in Northern Taiwanese older adults at high risk of cognitive impairment.

Method

A cross‐sectional, mixed‐methods approach was employed. Qualitative interviews with 10 stakeholders, including at‐risk older adults and community leaders in Northern Taiwan, informed the adaptation of the English Perceived Neighborhood Cohesion Scale into a 13‐item Chinese version. Quantitative phase applied the convenient sampling method to recruit 125 older adults with high risk of cognitive impairment in communities in Northern Taiwan. A trained research assistant administered the revised scale face‐to‐face to 125 older adults identified as high‐risk for cognitive impairment. Psychometric properties assessed included expert validity (Content Validity Index), exploratory factor analysis, internal consistency (Cronbach’s Alpha), and 7‐day test‐retest and inter‐rater reliability.

Results

The quantitative phase results are listed as follows. The participant demographic was 31.2% male and 68.8% female, primarily aged 70‐74 (27.2%) and ≥75 (27.2%). The Content Validity Index was 0.94. Exploratory factor analysis yielded a three‐factor solution: Trust in the Neighborhood (Cronbach’s Alpha = 0.84), Community Leader Action (Cronbach’s Alpha = 0.68), and Cohesion in the Neighborhood (Cronbach’s Alpha = 0.77). Overall internal consistency was high (Cronbach’s Alpha = 0.88), with excellent 7‐day test‐retest (0.92) and inter‐rater reliability (0.99).

Conclusion

The CMPNCS exhibits strong psychometric properties, making it a valuable tool in nursing research. It enables the assessment of neighborhood cohesion and the exploration of its relationship with cognitive function in at‐risk older adults. The findings can guide community health nurses in enhancing perceived community cohesion and developing tailored environmental interventions for this population.
Immunohistochemical study of the bcl‐2 in the pyramidal layer of the hippocampus in rats in hypertensive encephalopathy modeling
Authors: Mednikov Dmitry , Smirnov Alexey Vladimirovich , Tyurenkov Ivan Nikolaevich
Published: January 2025

Background

Closely related to the subfamily of proapoptotic proteins is the antiapoptotic protein bcl‐2, which acts as an intracellular blocker of the mitochondrial apoptotic pathway. By inhibiting the action of effector caspases, as well as blocking the release of AIF and cytochrome C, Bcl‐2 prevents regulated cell death and ensures survival in conditions of damage.

Method

The study was performed on Wistar rats, which were subjected to gravitational overloads (9g) in the caudocranial vector for 5 minutes twice a day for 28 days.

Result

An immunohistochemical study using antibodies to bcl‐2 in a group of rats with simulated hypertensive encephalopathy revealed a heterogeneous positive cytoplasmic reaction, mostly moderately expressed. In individual pyramidal neurons and glial cells, expression was mosaic in nature, where both dusty accumulation of IRM of weak intensity and deposits of more pronounced intensity were detected. Visually more intense staining was detected in neurons with deformed perikarya against the background of pronounced edema. Increased expression of bcl‐2 was also manifested in an increase in the relative area of the IRM. In CA1 of rats of the study group, this the indicator increased by 3.9% compared to the control (p<0.01). The most significant increase in the relative area of bcl‐2‐positive material was detected in CA2 and CA4, increasing, respectively, compared to the control by 5.6% (p<0.01) and 5.7% (p<0.01).

Conclusion

Higher activity of bcl‐2 in the CA1 and CA3 zones may be one of the factors for the greater stability of CA2 and CA4 in relation to CA1 and CA3.
The Association between Comorbidities and Cognitive Function: Findings from the Health and Retirement Study
Authors: Su Yan‐Jhu , Alberth Andrew , Rataj Alison C , Stam Elisabeth
Published: January 2025

Background

Cognitive function has been linked to factors including physical health and individual characteristics (e.g., race, ethnicity). However, few studies have examined these associations simultaneously. Therefore, this study examined the relationship between chronic conditions and cognitive function, and whether this differed for people across race and ethnicity among adults 65 years old and older in the United States.

Method

This cross‐sectional study uses data from the 2018 Health and Retirement Study (HRS). The sample includes adults, age 65 years and older, who were employed in 2018 (N = 8,310). The main dependent variable is respondents’ cognitive function (TICS‐35) in 2018 and the independent variable is the different chronic illness conditions and chronic illness count. Race and ethnicity are assessed as moderators. Ordinary least squares (OLS) regression models are utilized in this investigation.

Result

The results show that individuals with chronic lung disease such as chronic bronchitis or emphysema (b = ‐.56, p = .001), stroke (b = ‐.56, p<.001), or psychological issues (b = ‐.71, p<.001) had lower cognitive function scores than other individuals. Moreover, racial and ethnic differences were observed, specifically older Black adults with psychological issues scored lower on cognitive function scores when compared to White older adults (b = ‐.73, p = .075). Older adults with more chronic illnesses had a lower cognitive function score (b = ‐.11, p = .01) and racial and ethnic differences were observed as well, specifically older Hispanic adults with more chronic illness had lower cognitive function than White older adults (b = ‐.25, p = .035)

Conclusion

Findings demonstrate that people with more chronic illnesses may experience lower cognitive functioning, and racial and ethnic minorities may be particularly more vulnerable. Therefore, the prevention of chronic diseases plays an extremely important role in the cognitive health of older adults, specifically for vulnerable populations. Additionally, for racial and ethnic minorities, more emphasis may need to be placed on the prevention of chronic diseases. Policies aimed at preventing disease and promoting healthy lifestyles may also help improve cognitive functioning.
Unravelling Frontotemporal Dementia: Exploring the GABA and Glutamate Hypothesis through Semantic Deficits
Authors: Ilchovska Zlatomira Georgieva , Hosseini Akram A. , Jung JeYoung
Published: January 2025

Background

Semantic cognition refers to our ability to manipulate and generalize knowledge and plays a critical role in communication and daily activities. Therefore, impairments in semantic cognition can have a severe impact on quality of life (e.g., dementia). Frontotemporal dementia (FTD) is the cause of 12.5‐16.5% of all degenerative dementias. It is a heterogeneous group of clinical syndromes marked by progressive neurodegeneration of the frontal and temporal lobes – key regions for semantic cognition. Recent studies highlight the importance of addressing neurotransmitter deficits in FTD, particularly in glutamate and GABA. Though pathologically distinct, FTD syndromes share common neurotransmitter deficits – ‘GABA and glutamate hypothesis of FTD’. We investigate this hypothesis by linking GABA and glutamate changes with semantic deficits in FTD patients.

Methods

We utilized MR spectroscopy, a non‐invasive, in‐vivo technique, to measure neurochemicals, including GABA and glutamate, in the brain. Our study involved 7 FTD patients, 2 typical Alzheimer’s disease (AD) patients with a symptomatic amyloid status serving as a control patient group (expected to show general cognition deficits but not specifically semantic ones, neither semantic‐specific neurotransmitter changes like those in the FTD), and 23 age‐matched healthy controls (HC). We assessed neurotransmitter concentrations in the temporal and frontal cortex, conducted computerized semantic tasks, and administered cognitive batteries assessing language, memory, attention, and executive function.

Results

FTD patients showed deficits in language, memory, and executive function compared to AD patients and HCs (see Figure 1). AD patients also showed decreased general cognition compared to HC. Importantly, FTD patients performed the semantic task less effectively than ADs and HCs (see Figure 2). The balance between excitation and inhibition (EIB = glutamate/GABA) was significantly decreased in the temporal lobe in FTD patients compared to HCs (see Figure 3).

Conclusions

FTD demonstrated cognitive deficits in language, memory, and executive function, along with decreased semantic task performance and reduced EIB in the temporal lobe. These preliminary findings support the GABA and glutamate hypothesis of FTD. Ongoing data collection on this CogNID project (IRAS reference: 250525, clinical trial reference: NCT03861884) will provide additional results, with more patient data to be presented at the AAIC conference.
Life’s Essential 8, cardiovascular health, and incident dementia in diverse US adults of the Northern Manhattan Study
Authors: Elfassy Tali , Gardener Hannah , Gutierrez Jose , Agudelo Christian , Wright Clinton B. , Elkind Mitchell S.V. , Levin Bonnie , Rundek Tatjana
Published: January 2025

Background

The American Heart Association’s Life Essential 8 (LE8) are a set of eight simple health metrics used to define cardiovascular (CV) health and promote healthy behaviors. High CV health is associated with a lower risk of CV disease. Our objective is to determine whether LE8 and CV health are associated with incident dementia in diverse adults.

Methods

We used data from 877 participants of the Northern Manhattan Stroke study, a population based multi racial/ethnic cohort of adults age 40 and older. Information was collected on behavioral factors (diet, smoking status, physical activity, sleep duration) and clinical factors (BMI, blood pressure, cholesterol, fasting glucose, and medication use) which were measured and used to estimate a LE8 score (range: 0 to 100). CV health was defined as low (LE8 < 50), moderate (50<LE8≤80) or high (LE8≥ 80). Incident dementia was adjudicated during follow‐up by neuropsychological assessments. We used logistic regression analyses to assess the association between LE8 and CV health with incident dementia adjusting for age, sex, race/ethnicity, and education.

Results

Mean age in the sample was 64 (SD: 8.2), 59.9% were female, 15.4% were non‐Hispanic White, 17.8% were non‐Hispanic Black, and 64.7% were Hispanic. Mean LE8 was 60.8 (SD: 12.4) and 18% had low CV health, 78.9% had moderate CV health, and 6.0% had high CV health. Over an average of 8.9 years of follow‐up, 145 people developed dementia. From multivariable adjusted models, each 10 unit decrement (worse LE8 score) was associated with a 19% higher odds of developing dementia (OR: 1.19, 95% CI: 1.02, 1.40). Compared with high CV health, odds of dementia was greater by 203% among those with low CV health (RR: 3.03, 95% CI: 1.07, 8.56), but not among people with moderate CV health (OR: 1.46, 95% CI: 0.55, 3.93).

Conclusion

Only 1 in 20 adults in the study had high CV health. Poor CV health defined by the new LE8 metric substantially increases risk for developing dementia. Our results show that improvements in CV health factors are critical for prevention of dementia and further studies on health metrics are warranted.
Influence of biological sex on early cognitive performance in FTLD mutation carriers: an ALLFTD study
Authors: Castro Jesús Garcia , Rubio‐Guerra Sara , González Judit Selma , Memel Molly B , Dols‐Icardo Oriol , Bejanin Alexandre , Belbin Olivia , Fortea Juan , Alcolea Daniel , Carmona‐Iragui Maria , Barroeta Isabel , Santos‐Santos Miguel A , Sánchez‐Saudinós Mª Belen , Sala Isabel , Heuer Hilary W. , Staffaroni Adam M. , Casaletto Kaitlin B. , Boeve Brad F. , Boxer Adam L. , Rosen Howard J. , Lleo Alberto , Illán‐Gala Ignacio
Published: January 2025

Background

Accumulating evidence indicates that biological sex may influence clinical manifestation within the spectrum of frontotemporal lobar degeneration (FTLD), implying differences in cognitive reserve. Nonetheless, investigations into the impact of biological sex during the preclinical and minimally symptomatic stages of FTLD are lacking.

Method

We included 275 mutation carriers (158 females; 127 with C9orf72, 68 with GRN, and 80 with MAPT mutations) and 161 non‐carrier familial controls (97 females) from the ALLFTD Consortium (Staffaroni et al., Nat Medicine 2022). Participants underwent magnetic resonance imaging (MRI; 348 baseline, 338 longitudinal) and neuropsychological evaluations (394 baseline, 507 longitudinal). Behavioral symptoms were characterized with the Revised Self‐Monitoring Scale (RSMS) and the Neuropsychiatric Inventory (NPI severity scores). MRI‐derived regional volume estimates (RVE) were computed. Cognitive measures and RVE were normalized against sex‐matched controls. Cognitive composites (language, executive function, and visuospatial function) were calculated by averaging raw scores for each domain. Clinical characteristics and RVE comparisons were made between male and female participants. We adopted the residuals approach to explore behavioral and cognitive reserve by fitting a linear regression model for executive z‐scores as the response value and age, education, and RVE as explanatory variables.

Result

In mutation carriers, sex was not a significant differentiator in age, education level, disease severity, or mutation frequency. Most mutation carriers (188, 68%) were asymptomatic or mildly symptomatic at baseline. However, female mutation carriers exhibited significantly lower visuospatial performance at baseline (Cohen's d = ‐0.34, 95% CI[‐0.58, ‐0.09], p=.001). This difference remained significant among asymptomatic GRN mutation carriers (Cohen’s d = ‐0.73, 95% CI[‐1.22, ‐0.23], p=0.003) but not in other mutations. Following the residuals approach, female mutation carriers showed higher executive performance than males for the same amount of both frontotemporal and global atrophy as quantified by RVE (Cohen's d=0.45, 95 % CI[0.22, 0.67], p<.001). The observed higher executive reserve in women was particularly pronounced in C9orf72 carriers (Cohen's d=0.77, 95% CI[0.35, 1.20], p<.001) but not significant in GRN (p=0.48) and MAPT carriers (p=0.07). No differences in behavioral reserve reached statistical significance.

Conclusion

Female sex might modulate early cognitive performance and confer higher executive reserve in FTLD mutation carriers.
Cortical correlations of CSF Neurogranin, VILIP‐1, Alpha‐Synuclein and NFL in SCD and MCI according to amyloid status
Authors: Guimarães Emanuel R. , de Campos Brunno , Ribeiro Isadora Cristina , Aventurato Ítalo Karmann , da SIlva Marjorie Cristina Rocha , Rizzi Liara , Balthazar Marcio
Published: January 2025

Background

Alzheimer's disease (AD) pathophysiology is complex and not completely known. Emerging new biomarkers that evaluate synaptic function (VILIP‐1, neurogranin), co‐pathology (alpha‐synuclein), and neurodegeneration (NFL) are potential candidates to be incorporated into the early AD diagnosis. To better understand the relevance of these biomarkers, we evaluated the correlations between their CSF concentrations with whole‐brain grey matter volumes in SCD and MCI, according to their amyloid status (A‐ or A+).

Method

75 participants diagnosed with SCD or MCI were included, 30 A‐ and 45 A+. They all underwent comprehensive neuropsychological assessment, CSF analyses (Roche Elecsys), and volumetric 3T MRI (Philips Achieva). Voxel‐based morphometry was used to quantify brain volumes through CAT12 running on MATLAB 2019b. Partial correlation analysis between CSF biomarkers and cortical volumes was performed with SPSS 22, adjusting for age and sex.

Result

Significant correlations were found in the A‐ but not in the A+ group. NFL and hippocampus (r=0.40, p =0.028); VILIP‐1 and superior temporal gyrus (r= ‐0.38, p=0.035), and superior frontal gyrus (r=‐0.40, p=0.025); alpha‐synuclein and hippocampus (r= ‐0.39, p=0.036), middle frontal gyrus (r=‐0.375, p=0.049), and superior temporal gyrus (r=‐0.478, p=0.01).

Conclusion

We found different patterns of correlations between brain anatomy and emerging biomarkers, according to amyloid status, in the very early stage of the neurodegenerative process. Interestingly, these correlations were found only in the amyloid‐negative group, which might suggest that different pathological processes involving synaptic function, neurodegeneration, and co‐pathology occur in suspected non‐Alzheimer pathophysiology cases.
Considerations for implementation of Alzheimer’s disease blood‐based biomarkers in clinical care based on recently updated NIA‐AA criteria
Authors: Mielke Michelle M.
Published: January 2025

Background

The National Institute on Aging (NIA) and the Alzheimer’s Association (AA) recently updated their 2018 recommendations for the diagnosis and characterization of Alzheimer’s disease (AD), which include the use of blood‐based biomarkers (BBMs) for the differential diagnosis of AD. BBMs of amyloid‐beta, phosphorylated tau, neurodegeneration, inflammation, and alpha‐synuclein were defined, with a highlighted need for blood biomarkers of vascular brain injury. Many questions remain regarding how to implement these biomarkers for clinical care including diagnosis and to assess eligibility for disease modifying treatments (DMT).

Method

Using examples from published and unpublished studies, the barriers to implementation of the use of AD BBMs will be synthesized. Additional discussion will focus on the current status and future discovery and implementation of non‐AD BBMs for vascular injury, inflammation, and alpha‐synuclein.

Result

There are unique barriers and facilitators for the use of BBMs in primary and secondary care to diagnosis AD and assess DMT eligibility. Many questions remain regarding how to utilize the BBMs for disease staging in clinical care as compared to the research setting, which BBMs to use and when, as well as how to implement the BBMs at the population level.

Conclusion

Advancing technology has led to the clinical use of BBMs to diagnose AD and assess treatment eligibility. Several considerations and steps are needed before these blood biomarkers can be implemented for use at the population level.
Optimizing Mealtime (OPTIMAL): A Pilot Trial of a Person‐Centered Care Program in Nursing Home Care Staff and Residents with ADRD
Authors: Liu Wen , Suh Heather , Williams Kristine N , Galik Elizabeth , Resnick Barbara , Buckwalter Kathleen , VanHaitsma Kimberly S , Rakel Barbara
Published: January 2025

Background

Nursing home (NH) residents with dementia commonly experience mealtime behaviors that negatively impact nutrition and function. Residents do not receive person‐centered mealtime care (PCMC) due to multilevel factors one prioritized modifiable factor is lack of effective PCMC programs. This study aimed to develop a PCMC program and test its feasibility, acceptability, usefulness and preliminary efficacy.

Method

We developed Optimizing Mealtime (OPTIMAL), a multifaceted, evidence‐based, theoretically grounded PCMC program with five components: community stakeholder engagement, environment/policy assessment/modifications, staff education, individualized care planning, and ongoing motivation. A mixed methods design (single‐group repeated measures design followed by stakeholders’ interviews) was used. Repeated measures (resident mealtime resistive behaviors, mealtime functional impairments, eating independence, and food intake amount) were collected at baseline (T1), and at 6‐week (T2) and 12‐week (T3) post baseline.

Result

OPTIMAL was delivered in one NH, where 95 direct care staff received education (age = 45±12.1 years, 13% male, 15% non‐white, 19% Hispanic, 89% experienced challenges with mealtime care), and 17 residents with moderate‐to‐severe dementia were observed (age = 74±7.9 years, 88% male, 12% non‐white, 6% Hispanic). We achieved high recruitment (74%, 77%) and retention (94%, 99%) rates for residents and staff. Stakeholders felt OPTIMAL was useful for staff who provide care to residents, with and without ADRD, who need assistance and/or experience behavioral symptoms at mealtime. Further, videotaped observations of dyadic mealtime interactions (N = 265) at three time points supported preliminary efficacy of OPTIMAL: 1) resident mealtime resistive behaviors and functional impairments decreased from T1 to T2 and T3; 2) resident eating independence showed slight decline over time; and 3) resident food intake amount (grams/meal) increased from T1 to T2 and T3.

Conclusion

Findings supported feasibility, acceptability, and usefulness of OPTIMAL in NH staff and residents with dementia. OPTIMAL shows preliminary efficacy
in decreasing resident mealtime resistive behaviors and functional impairments, preserving eating independence, and increasing food intake amount in NH residents with moderate‐to‐severe dementia – a vulnerable population that typically experience deteriorations as their cognition declines. Future large‐scale trials are needed to test the efficacy of OPTIMAL in residential care settings.
Investigating Spatial Characteristics of Brain Atrophy in Alzheimer’s and LATE neuropathology
Authors: Saifullah Khalid , Ridwan Abdur Raquib , Bennett David A. , Schneider Julie A. , Arfanakis Konstantinos
Published: January 2025

Background

Alzheimer’s disease neuropathologic change (AD‐NC) and limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) are common in older adults and have been associated with brain atrophy, cognitive decline, and dementia. Since AD‐NC and LATE‐NC are often comorbid and due to the fact that LATE‐NC can only be detected at autopsy, in this work, we combined deformation‐based morphometry (DBM) on ex‐vivo brain MRI and detailed neuropathological evaluation in a large number of community‐based older adults to investigate the difference in brain atrophy patterns associated with AD‐NC and LATE‐NC.

Method

Cerebral hemispheres from 912 older adults participating in four longitudinal, clinical‐pathologic cohort studies of aging were included in this work: MAP, ROS, MARS, and AA Core of the Rush Alzheimer’s Disease Research Center (Rush ADRC) (Figure 1). All hemispheres were imaged ex‐vivo on 3T clinical MRI scanners approximately 1‐month postmortem while immersed in 4% formaldehyde solution. T2‐weighted images of all hemispheres were non‐linearly registered and logarithm of the Jacobian determinant (LogJ) of the deformation field was calculated in each voxel. Following ex‐vivo MRI, the pathologies that were assessed were AD‐NC, LATE‐NC, Lewy bodies, gross infarcts, microscopic infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy. AD‐NC‐pos was defined as moderate or severe AD‐NC according to the NIA‐AA criteria, and LATE‐NC‐pos was defined as LATE‐NC stages 2 or 3.

Voxel‐wise linear regression was used to test the association of the deformations observed in the smoothed log Jacobian maps with the four different groups, controlling for all other neuropathologies, demographics, postmortem intervals, and scanner. We used 5000 permutations, and statistical significance was set at p<0.05 after family wise error (FWE) correction.

Result

Both the AD‐NC‐pos LATE‐NC‐neg group (Figure 2a) as well as the AD‐NC‐neg LATE‐NC‐pos group (Figure 2b) were associated with lower tissue volume mainly in medial temporal lobe structures. The AD‐NC‐pos LATE‐NC‐pos group (Figure 2c) showed substantially lower volume in the temporal, frontal, and parietal lobes. Interestingly, the AD‐NC‐neg LATE‐NC‐pos group showed lower volume in the anterior portion of the hippocampus than the AD‐NC‐pos LATE‐NC‐neg group (Figure 2d).

Conclusion

The findings suggest that in the presence of LATE‐NC, the volume of the hippocampus cannot serve as a marker of AD‐NC.
Efforts to increase the racial and ethnic and socioeconomic diversity of the Adult Changes in Thought study cohort
Authors: Gatto Nicole M , LaCroix Andrea Z. , Tom Sarah E. , Ralston James , Crane Paul K. , Muiruri Roxanne , Sankaran Sundary , Shaw Pamela A. , Gibbons Laura E. , McEvoy Linda K.
Published: January 2025

Background

The Adult Changes in Thought (ACT) study is an ongoing population‐based prospective cohort study that began in 1994 and aims to identify risk and preventive factors for dementia. ACT randomly selects and enrolls Kaiser Permanente Washington (KPWA) health plan members age ≥ 65 years. Historically, the cohort make up has been 88% non‐Hispanic White participants. A core aim of the ACT U19 is to expand enrollment with a specific emphasis on increasing racial, ethnic, and socioeconomic diversity of study participants. A set target is to enroll 600 new members from historically minoritized groups by April 2026, including Asian, Black and Hispanic participants, such that these groups represent > 20% of the active sample (n = 3,000).

Method

To meet our target, we implemented a series of changes to our recruitment processes including revising recruitment materials to improve their informativeness, oversampling racial and ethnic groups, and locating a second ACT research clinic site in the socioeconomically diverse southeastern region of Seattle to expand our catchment area. We will examine how our newly enrolled cohort members compare to the KPWA population with respect to age, sex, area deprivation index (ADI) and health status.

Result

For the one year‐period spanning December 2022 through December 2023 when modifications to recruitment began to be rolled out and participant visits were restarted after COVID‐19, we enrolled 320 new participants with a racial and ethnic distribution of 25% Asian, 12% Black, 16% Hispanic, 2% Pacific Islander or Native American and 49% White.

Conclusion

Broader representation of diverse participants within ACT will make study findings more generalizable to the KPWA source population.
Preliminary Validation of the Malayalam‐version of the Cognitive Change Index
Authors: Stimmel Marnina B , Emmeline Ayers , Verghese Joe , Weiss Erica , Rabin Laura
Published: January 2025

Background

With the worldwide geriatric population steadily increasing, identifying older adults in need of treatment for cognitive difficulties is imperative. Limited specialty resources makes it particularly important to identify which individuals would most benefit from further evaluation and treatment, including in countries where dementia care is limited, such as India. Self‐report measures are timely and cost effective tools that can assist providers in identifying individuals at risk of cognitive decline. The Cognitive Change Index (CCI), a 20‐item measure of self‐perceived cognitive functioning, has been validated in English and Spanish. In the present study, we present preliminary findings on the translated, Malayalam‐version of the CCI.

Method

500 Malayalam‐speaking older adults (mean age = 68.8[SD = 5.4]; 62% male; mean education = 9.6 years[SD = 3.5]) completed the CCI, Addenbrooke’s Cognitive Examination‐III (ACE‐III) and Geriatric Depression Scale‐30 item (GDS‐30) as part of the Kerala Einstein Study, an ongoing longitudinal community‐based study of pre‐dementia syndromes in Kerala India. The CCI was translated and back‐translated for accuracy. Means and SDs were calculated for various baseline demographics. Pearson correlation and t‐tests (and cohen’s d for effect size) were used to compare the CCI to demographic variable and to GDS‐30 and ACE‐III performances.

Result

Higher endorsement on the CCI was strongly correlated with lower ACE‐III performances (r(498) = ‐.66, p <.001), and weakly correlated with higher GDS‐30 scores (r(498) = .33, p <.001). The CCI was not correlated with age or education. While men endorsed significantly higher CCI scores (mean = 37.7; SD = 16.9) compared to women (mean = 34.8; SD = 15.3), t(498) = ‐1.925, p = .027, the effect size was small (Cohen’s d = ‐.178) and the difference not clinically meaningful. When gender and GDS‐30 were controlled, the correlation between CCI and ACE‐III remained strong (r(498) = ‐.66, p <.001).

Conclusion

Preliminary data showed confirmatory performance of the Malayalam‐version of the CCI in identifying individuals at risk for cognitive impairment (i.e., lower performances on a cognitive screener), and was not meaningfully influenced by age, gender, or education. Although additional validation is needed, this preliminary analysis suggests that the CCI could be a useful self‐report measure for providers to use with Malayalam speaking older adults to ascertain possible cognitive impairment.
Developing a predictive model for deterioration in long‐term care level among Japanese older adults with mild cognitive impairment and dementia: NCGG‐STORIES
Authors: Uchida Kazuaki , Sugimoto Taiki , Jin Xueying , Nakagawa Takeshi , Ogata Soshiro , Kiyoshige Eri , Fujita Kosuke , Kuroda Yujiro , Sakurai Takashi , Saito Tami
Published: January 2025

Background

To enhance the well‐being of individuals with dementia, it is crucial to minimize the risk of deterioration in long‐term care needs. This study aimed to identify factors and construct predictive models for deterioration in long‐term care (LTC) levels in Japanese older adults with Mild Cognitive Impairment (MCI) and dementia.

Method

This retrospective cohort study utilized the data from a memory clinic‐based cohort study (NCGG‐STORIES) and individual LTC insurance data provided by three municipalities. We included older adults aged ≥ 65 with MCI or dementia who had LTC levels ≤1 and resided in these municipalities at the initial visit. We used the certified LTC levels of the LTC insurance (seven care levels based on the severity of their physical and cognitive disability), and the outcome was the number of days from the initial visit to the new occurrence of LTC level ≥ 2, approximately equating to any care needs in basic activities of daily living (BADL). Demographic, lifestyle, functional, behavioral, and psychological factors assessed at the initial visit were included as potential predictors. The selection of predictors involved a backward stepwise Cox regression model, and the predictive model was formulated using a regression coefficient‐based scoring approach. Discrimination and calibration were assessed via Harrell’s C‐statistic and a calibration plot, respectively.

Result

We analyzed 605 patients (mean age, 79.1 years; 57.7% women). During a mean follow‐up of 3.4 years, 329 older adults were newly certified LTC Level ≥ 2. Among possible sociodemographic and clinical variables, age, BADL, behavioral and psychological symptoms of dementia (BPSD), care burden, and history of fall were selected according to the analysis. The resulting predictive model exhibited good discrimination and calibration (Harrell’s C‐statistic [standard error] = 0.748 [0.013]).

Conclusion

This study clarified some modifiable factors with deterioration in long‐term care needs, such as BPSD, care burden, and history of fall. Furthermore, the developed predictive model may have an effective discriminative ability for the new occurrence of LTC level ≥ 2 and holds potential for implementation in individuals with MCI and dementia referred to a memory clinic in Japan.
Basic Performance of highly sensitive Chemiluminescent Enzyme Immunoassay for β‐Amyloid 1‐40 and β‐Amyloid 1‐42
Authors: Nakazawa Takuya , Sakurai Yuji , Shima Yoko , Imai Yuka , Aoyagi Katsumi , Nojima Hisashi
Published: January 2025

Background

Alzheimer's disease (AD) is the most common cause of a decline in cognitive ability. The pathogenesis of AD involves the deposition of β‐amyloid (Aβ) plaques and the formation of neurotoxic oligomers of Aβ protein. This leads to neurofibrillary tangles composed of phosphorylated Tau proteins, neuroinflammation, loss of nerve cells and synapses, and ultimately dementia. Recent research suggests that the Aβ1‐42/Aβ1‐40 ratio in plasma can predict amyloid deposition in the brain. However, the small difference between amyloid‐positive and ‐negative subjects results in a very low total allowable error. Therefore, the assay system with high reproducibility is required. Here, we improved Aβ1‐40 and Aβ1‐42 assays in Lumipulse and report the basic performance.

Method

The Lumipulse system is a fully automated chemiluminescent enzyme immunoassay platform that processes samples in approximately 30 minutes. This assay uses two monoclonal antibodies to capture and detect Aβ1‐40 or Aβ1‐42. Baseline performance was analyzed in a limited set of characterized patient samples. The analytical study included a series of plasma samples (K2EDTA) at various concentration levels, and each analyte was tested in multiple replicates, sized to suit the various parameters tested.

Result

As shown previously on other LUMIPULSE assays, variability (within‐ and between‐run) was found to be low. An acceptable Limit of Quantification or functional sensitivity was obtained based on the evaluation of low Aβ1‐40 and Aβ1‐42 concentrated serum samples. No cross reactivity toward other Aβ fragments was observed. In the frozen‐thawed samples, no effect was observed for several times.

Conclusion

These studies showed promising performance with less variability, suggesting that these Aβ assays could be useful in screening appropriate patients for AD therapy.
Adverse childhood experiences and subjective cognitive decline among transgender adults
Authors: Chiow Jobina , Cicero Ethan C.
Published: January 2025

Background

Adverse childhood experiences (ACEs) are associated with an increased risk of developing chronic health conditions later in life, including Alzheimer’s disease and related dementias (ADRD) and subjective cognitive decline (SCD), a self‐reported confusion and memory loss and one of the first clinical manifestations of ADRD. While ACEs and SCD have both been individually studied in transgender and nonbinary (TGN) adults, no study has examined the relationship between ACEs and SCD among this population. This study sought to establish the prevalence of ACEs and their association with SCD among TGN adults.

Method

2019‐2021 Behavioral Risk Factor Surveillance System (BRFSS) data, representing 16 U.S. states that assessed ACEs, SCD (confusion/memory loss happening more often/getting work over previous 12months), and self‐reported gender identity were used to determine the association between ACEs and SCD among TGN adults aged 45+ (N = 206). Pearson’s chi‐squared/Fisher’s exact tests assessed the association between ACEs (individual, categorical, sum score) and SCD. Crude and adjusted odds ratios (aOR) along with 95% confidence intervals (CI) were calculated to investigate the associations between ACEs (individual, categorical, sum score) and SCD.

Result

18% (n = 38) of TGN adults in the sample reported SCD, 60% (n = 120) experienced any ACE, 20% (n = 41) 1 ACE, and 18% (n = 37) experienced ≥4 ACEs. Nearly 50% experienced childhood abuse (n = 94) or household dysfunction (n = 92); the most prevalent ACE was verbal abuse by parent/adult in the home. Among those endorsing SCD, 34% (n = 13) reported ≥4 ACEs, 73% (n = 26) childhood abuse or household dysfunction (n = 27). Most ACES were significantly associated with and increased the risk of SCD, even after adjusting for BRFSS year, age, race, education, and employment. The odds of SCD increased 40% as the number of ACEs increased (aOR = 1.4, 95% CI:1.2‐1.6, p<0.0001). The odds of SCD were significantly higher with childhood abuse (aOR = 4.3, 95% CI: 1.88‐10.02, p<0.01) or household dysfunction (aOR = 4.7, 95% CI: 2.00‐11.07, p<0.01).

Conclusion

A lifecourse perspective is needed when examining the brain health of TGN adults. Childhood abuse and household dysfunction are risk factors for SCD. ACE screening/interventions for TGN youth are needed to help reduce the risk of SCD and cognitive impairment later in life.