bluuebunny/crossref_metadata_2025 huggingface dataset:
The amyloid PET status in Primary Progressive Aphasia
Authors: Shimizu Soichiro , Yamamoto Ryo , Inagawa Shoya , Takenoshita Naoto
Published: January 2025

Background

Primary Progressive Aphasia (PPA) is a clinical and symptomatic concept due to neurodegenerative diseases which language symptom was dominant from early clinical stage. PPA is categorized into 3 subtypes such as Progressive non‐fluent aphasia (PNFA), Semantic dementia (SD), and logopenic progressive aphasia (LPA). In this study, we compared the differences of PPA subtypes depend on amyloid PET results.

Method

We recruited PPA patients who underwent standard aphasia test (SLTA) as Japanese aphasia test, cerebrospinal fluid AD biomarker, and amyloid PET. We divided into Amyloid PET positive (A(+) PPA) and negative (A(‐) PPA) group. then we compared the characterization of SLTA results and CSF biomarker between two groups.

Result

A total of 15 patients were included. There were 7 patients in A (+) PPA groups (2 males and 5 females, age: 65.3±8.3 years), and 8 patients in A (‐) PPA group (6 males and 2 females, age: 66.6±11.2 years). Regarding cerebrospinal fluid AD biomarkers, a significant decrease in Aβ42/40 (p < 0.01) and significant elevation in P‐tau (p<0.01) was observed in the A (+) PPA group compared to the A (‐) PPA group. In SLTA, the A (+) PPA had LPA: 57% and transcortical sensory aphasia: 29%. on the other hand, A (‐) PPA group had PNFA: 38% and SD: 50%.

Conclusion

This study showed there is the possibility of SLTA may be useful to predict AD pathology in patients with PPA.
Factors associated with loneliness among Chilean family carers of people living with dementia
Authors: Miranda‐Castillo Claudia , Tapia‐Muñoz Thamara
Published: January 2025

Background

The risk of developing loneliness in informal carers of people with dementia is high. Individual and cultural factors might play a differentiated role in the explanation of loneliness. The aim of this study was to describe loneliness levels in a group of family carers in Chile and its associated factors.

Method

A sample of 283 Chilean carers was surveyed about loneliness (measured with the 3‐item of the revised UCLA scale) carer’s personality, and sociodemographic and health factors. Sociodemographic and clinical data from the person living with dementia was also reported by carers. Multiple linear regression models using bootstrap errors (1000 iterations) were carried out to determine predictors of loneliness.

Results

Carers were, on average, 59 years old, mostly women (79%), married or in a partnership (59%), with children (78%), and caring for a parent (54%) with Alzheimer’s Disease (74%). The average level of loneliness was 4.33 (range: 3‐9), and 12% of carers reported problematic loneliness (³6). Forty‐two percent of loneliness variance was explained by emotion‐focused coping, age, extraversion, neuroticism, gain, social support, and depressive and anxiety symptoms. In a final model, gain (Coef. ‐0.050; 95% CI: ‐0.085 to ‐0.015) and emotion‐focused coping were negatively associated with loneliness (Coef. ‐0.028; 95% CI: ‐0.050 to ‐0.006), whilst depressive symptoms were positive associated with loneliness (Coef. 0.089; 95% CI: 0.050 – 0.129).

Conclusions

Research usually focuses on negative aspects of caregiving. However, the perception of gain and emotion‐focused coping mechanisms used by carers can be protective factors against loneliness. Non‐pharmacological interventions might benefit from the development of those factors.
Associations Between Choroid Plexus Integrity and Cognitive Decline in Aging: Insights from Advanced MRI Analysis
Authors: Gong Zhaoyuan , Bilgel Murat , Faulkner Mary E , Bae Jonghyun , Laporte John P , Guo Alex , Resnick Susan M. , Egan Josephine M. , Bouhrara Mustapha
Published: January 2025

Background

The choroid plexus (CP), a vital component in the brain's ventricles, is crucial for cerebrospinal fluid (CSF) production and maintenance of the brain's physiological environment. It plays a key role in regulating neuroinflammatory responses, clearing harmful substances, producing neurotrophic factors and signaling molecules, and forming blood‐CSF barrier. Consequently, changes to the CP’s structural integrity could disrupt brain homeostasis and lead to cognitive impairment. Indeed, recent research has highlighted CP alterations in aging as well as in various cognitive disorders including Alzheimer's and Parkinson's diseases. This study investigates the correlation between the macrostructural and microstructural integrity of the CP and longitudinal cognitive changes in cognitively unimpaired individuals.

Method

116 cognitively unimpaired participants from the BLSA and GESTALT underwent advanced MRI, including relaxometry (T1 and T2) and diffusion tensor imaging (DTI), enabling the quantification of CP volume, fractional anisotropy (FA), and mean diffusivity (MD). Participants received cognitive assessments at visits preceding and concurrent with MRI scans (320 visits total) to measure memory, attention, executive function, verbal fluency, and processing speed (Table 1). Linear mixed‐effects models were used to analyze the association between MRI metrics and longitudinal cognitive changes, adjusting for age, sex, education, and race.

Result

Our study found that larger CP volume, elevated T1 and T2 values, and higher MD values, all indicative of compromised macrostructural or microstructural integrity, were associated with faster declines in various cognitive domains (Table 2). Particularly, the association was found in memory, verbal fluency, and processing speed for CP volume; in attention, executive function, and processing speed for T1 and T2 (Figure 1); and in attention, executive function, and processing speed for MD. Conversely, lower FA values, representing deteriorated microstructural integrity, correlated with accelerated decline in memory, attention, verbal fluency, and processing speed.

Conclusion

This study highlights a significant association between CP characteristics and cognitive decline in cognitively unimpaired individuals. These findings underscore the importance of the CP in cognitive health and emphasize the need for further research into the role of the CP in healthy aging, potentially opening new pathways for early detection and intervention in cognitive decline.
Rehabilitation participation and one‐year cognitive and affective changes in adult day service users with dementia
Authors: Tanaka Naofumi , Ouchi Yoshitaka , Wang Yin‐Jung , Kasuya Masashi
Published: January 2025

Background

Day care services provide various activities, including rehabilitation, to maintain and improve physical function and social participation of older people. However, the relationship between rehabilitation participation and emotional changes in older adults with dementia who use day care services is not well understood.

Method

The participants were 157 older adults living in the community who used day‐care services. Users with MMSE scores less than 10 at the initial and one‐year evaluation were excluded. Other assessments were the Geriatric depression scale‐15 (GDS‐15), the Apathy evaluation scale (AES) and the Short physical performance battery (SPPB). Rehabilitation participation was averaged over three consecutive days of use using the Pittsburgh Rehabilitation Participation Scale (PRPS), with the group with a PRPS greater than 4 points divided into two groups: good and poor rehabilitation participation groups. MMSE, GDS, AES and SPPB scores were compared using Wilcoxon’s rank sum test at the initial and one‐year follow‐up.

Result

The age of the participants was 83 ± 7 years and 43/114 were men/women. When further divided into three groups according to MMSE score (≥24, 20‐23 and 19‐10), the good rehabilitation group with an MMSE score of 19‐10 had a significantly higher AES score (p<0.001) and a significantly lower SPPB score (p = 0.016).

Conclusion

Among older adults with dementia using day care services, the group with good participation in rehabilitation was suggested to be at risk of increased apathy and reduced lower limb motor function after one year.
Identifying distinctive role of sarcopenia components for cognitive impairment with multimodal neuroimaging in non‐dementing older adults
Authors: Kim Sunghwan , Wang Sheng‐Min , Kang Dong Woo , Um Yoo Hyun , Yoon Han Min , Lee Soyoung , Choe Yeong Sim , Kim Regina EY , Kim Donghyeon , Lee Chang Uk , Lim Hyun Kook
Published: January 2025

Background

Although previous studies have demonstrated cognitive impairment in elderly individuals with sarcopenia and its neuronal substrates, there is no comprehensive model integrating multiple brain pathologies to predict cognitive impairment associated with sarcopenia. The aim of this study was to explore a comprehensive prediction model for cognitive impairment in sarcopenia using multimodal neuroimaging methods in non‐demented older adults.

Method

This cross‐sectional study used data from the Catholic Aging Brain Imaging Database study, a population‐based cohort study with magnetic resonance imaging (MRI) scans, positron emission tomography (PET) scans, and clinical data. A total of 528 non‐demented older adults, with or without sarcopenia, was included. We measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five‐times sit‐to‐stand test (5STS).

Result

Sarcopenia measures related to muscle mass, power and speed demonstrated significant partial correlations with cognitive function. Cortical thickness was significantly associated with muscle power (HGS; left superior temporal cortex) and speed (5STS; bilateral precentral and insula cortex), while amyloid‐beta (Aß) hand distinctive association with muscle mass (SMI). In the path model, brain atrophy was primarily influenced by SMI and HGS through Aβ retention and periventricular white matter hyperintensity (pvWMH), respectively, resulting in cognitive impairment. On the other hand, the 5STS directly affected brain atrophy, contributing to cognitive decline.

Conclusion

Sarcopenia sub‐domains, including muscle mass, power, and speed, showed distinctive associations with cognitive impairments related to Aß burden, pvWMH, and brain atrophy. Therefore, treatments targeting each sub‐domain should be considered to prevent cognitive decline associated with sarcopenia.
Association between dementia and functional activities of daily living: Mediating effect of visual functions
Authors: Jin Yeonju , Hong Ickpyo
Published: January 2025

Background

Dementia and visual impairment are both associated with reduced mobility and impaired functioning in activities of daily living (ADL) and instrumental activities of daily living (IADL). Cognitive deficits in older adults have more difficulties in performing daily tasks, increase the risk of fear of participation and may lead to injury (e.g. falls, fractures). However, it is not clear whether visual function mediates the association between dementia and functional activities of daily living.

Methods

A retrospective, cross‐sectional design that analyzed the mediating effects of visual functions on the association between dementia and functional activity of daily living. We retrieved 2,523 adults from the 3,817 survey participants in the 2022 National Health and Aging Trends Study. We utilized a series of path analysis models and estimated the mediating effects of visual functions between dementia and functional daily activities. We used the older adults with and without dementia as the independent variables. The mediators were total scores of three visual function variables (distance acuity, near acuity, contrast sensitivity). The dependent variables were the total scores of ADLs (e.g., dressing, toileting) and IADLs (e.g., laundry, shopping).

Results

Among the 2,523 older adults, 201 (8.0%) older adults with dementia, and 1,446 (57.3%) females. In the association between dementia and ADLs, the distance acuity revealed a significant mediation effect of 9.9% (direct effect β = 0.1875, p <0.0001, indirect effect β = 0.0205, p <0.0001), and IADLs showed a significant mediating effect of 8.8% (direct effect β = 0.2095, p <0.0001, indirect effect β = 0.0.0201, p <0.0001). In the association between dementia and ADLs, the contrast sensitivity revealed a significant mediation effect of 11.2% (direct effect β = 0.1847, p <0.0001, indirect effect β = 0.0233, p <0.0001), and IADLs showed a significant mediating effect of 11.6% (direct effect β = 0.2030, p <0.0001, indirect effect β = 0.0266, p <0.0001).

Conclusions

The study findings revealed the importance of visual function between dementia, ADL, and IADLs. Our findings indicated that healthcare professionals would need to provide interventions that consider visual functions to maintain functional activities of daily living in older adults with dementia.
Feasibility and effects of using location‐tracking devices to individuals living with dementia: An integrative review
Authors: Kim Jayeong , Hwang Mina , Hwang Yeji
Published: January 2025

Background

Wandering is a common issue among individuals living with dementia. This behavior often leads to increased worry for family caregivers, as those with dementia are at a heightened risk of becoming lost. Location‐tracking devices have potential as effective tools for providing independence to individuals living with dementia while reducing the risk of them getting lost. However, there is limited knowledge regarding the effectiveness of these devices specifically for people living with dementia. This study aims to examine the feasibility and effects of using location‐tracking devices in individuals living with dementia.

Methods

An integrative review was conducted using five databases: PubMed, Embase, Web of Science, CINAHL, and Scopus. Literature published up to August 2023 was screened for review. The inclusion criteria for a full‐text review were as follows: Empirical studies which (1) applied location‐tracking devices, (2) explored the effects of applying these devices, (3) involved a population of individuals living with dementia or their caregivers, and (4) were published in peer‐reviewed journals. Among the 1,429 studies initially identified, 10 studies were ultimately included in the review.

Results

The severity of cognitive impairment in the study participants varied across the studies. The duration of using the location‐tracking devices also varied from 1 day to 3 years. The location‐tracking devices were either worn on a belt, on the wrist as a watch, carried in a pocket, or embedded in mobile phones. Overall, these devices proved beneficial for both individuals living with dementia and their family caregivers. For individuals living with dementia, the devices provided greater independence when going outside and enhanced their sense of safety. For caregivers of individuals living with dementia, the devices alleviated concerns about their loved ones getting lost.

Conclusions

Location‐tracking devices have the potential to increase independence in individuals living with dementia and to lessen psychological stress among family caregivers. Researchers and stakeholders need to put more effort into encouraging the use of location‐tracking devices and minimizing the barriers.
A Machine Learning Approach Utilizing Normal‐appearing white matter Amyloid uptake for Amyloid Positivity Classification and Clinical progression prediction
Authors: Jo Sungman , Han Ji Won , Kim Ki Woong
Published: January 2025

Background

Amyloid positron emission tomography (PET) positivity is usually determined using visual assessment or a cutoff for standardized uptake value ratio (SUVR) based on cortical amyloid uptake. Our study aimed to develop and validate a machine‐learning based method for classifying amyloid PET positivity utilizing amyloid uptake in cerebral normal‐appearing white matter (NAWM).

Method

We analyzed Florbetaben (FBB) PET and MRI data from 813 participants aged 50 and over, recruited from dementia clinics of Seoul National University Bundang Hospital and the Korean Longitudinal Study on Cognitive Aging and Dementia cohort. Using global cortical composite SUVR and the NAWM Dominance Ratio (NDR; ratio of global SUVR to NAWM SUVR), we developed a machine‐learning algorithm called Gaussian Mixture Model NDR (GMM NDR). This algorithm iterates through two mixture components to categorize individuals as amyloid‐positive (A+) or negative (A‐). We compared the classification performance of GMM NDR to a conventional SUVR cutoff (0.96) using confusion matrices, receiver operating characteristic (ROC) analysis, and visual assessment as the gold standard. Additionally, we explored which classification method, among the three, best predicted clinical progression in individuals with discordant amyloid positivity across methods.

Results

The GMM NDR method demonstrated accuracy, sensitivity, specificity, and Youden’s index of 0.936, 0.988, 0.897, and 0.885, respectively, while the global SUVR method reported similar values of 0.941, 0.974, 0.916, and 0.890 for these metrics. The area under the curve (AUC) for each method were found to be comparable (0.943 for GMM NDR, 0.945 for global SUVR, p = 0.818). Among 59 participants with discrepancies in amyloid positivity across three methods, only the GMM NDR‐identified A+ group showed more clinical progression than the A‐ group (71.7% vs. 33.3%, p = 0.02). Logistic regression revealed a significant association between GMM NDR positivity and clinical progression (OR = 11.42, 95% CI = 1.105 – 117.92, p = 0.041), not observed in other methods.

Conclusion

The GMM NDR method demonstrates both robust classification accuracy for amyloid positivity and superior ability to predict clinical progression compared to traditional methods. This suggests its potential as a sensitive marker for monitoring disease progression and informing treatment decisions in neurodegenerative diseases.
Noun‐Classifier as a Semantic Cue for Lexical Retrieval Therapy for svPPA patients: Treatment Evidence Supported by a Single‐case, Multiple Baseline Analysis
Authors: Chen Lorinda Li‐Ying Kwan
Published: January 2025

Background

Lexical retrieval therapy (LRT) has been proven to be an effective speech therapy for individuals with semantic variant primary progressive aphasia (svPPA) and semantic cue plays an important ingredient in LRT. In recent findings, differential performance in using and choosing noun‐classifiers amongst Chinese individuals with the three subtypes of PPA were observed. The current study aims to explore the treatment effect of employing noun‐classifier as a semantic cue of LRT for Cantonese‐speaking svPPA.

Method

A single‐case, multiple‐baseline intervention study, modified lexical retrieval therapy using noun classifiers was conducted on two native Cantonese speakers (one male aged 74 and one female aged 76) diagnosed with svPPA. Eighteen sessions with daily home practice were conducted. Treatment outcomes were measured by naming accuracy and were measured at timepoints of pre‐treatment, immediate post‐treatment, and an additional 4 to 6 weeks post‐treatment (follow‐up stage). Primary and secondary outcome measures were the gain in accuracy of the naming of trained and untrained stimuli after therapy and at the follow‐up stage. One‐way ANOVA repeated measure was performed to demonstrate changes in treatment outcomes across time.

Result

Both participants showed significant improvement (F(2, 142) = 11.48, p = .000 and F(1.60, 113.39) = 25.07, p = .000 for the two participants respectively) in naming trained stimuli in immediate post‐treatment with a large effect size (η2 = .14 and .26 for male and female participant respectively). Generalization to untrained stimuli was shown in immediate post‐treatment measurement (F(1.47, 104.28) = 12.91, p = .000 and F(1.51, 107.38) = 35.18, p = .000 for the two participants respectively) also with a large effect size (η2 = .15 and .33 for the two participants respectively). Maintenance over six weeks after treatment was recorded for both trained and untrained stimuli for both participants. There was statistically significant improvement in naming accuracy for trained stimuli (F(1.27, 90.31) = 15.58, p = .000 for male participant and F(1.23, 87.04) = 37.95, p = .000 for female participant) in 4‐week and 6‐week follow‐up as compared to pre‐treatment with large effect size (η2 = .18 and .35 for the two participants respectively).

Conclusion

This study provides evidence for using noun‐classifiers as semantic cues in LRT for Chinese svPPA.
Prevalence of Unmet Care Needs of community based People with Dementia and their caregivers in Lusaka
Authors: Simushi Faith , Tanner Jeremy A. , Zimba Stanley , Saylor Deanna
Published: January 2025

Background

Globally, 47.5 million people were living with dementia in 2015. This figure is expected to reach 75.6 million in 2030, and over 135 million by 2050, with Sub‐Saharan Africa being among the regions expected to have the greatest future increase in dementia incidence and prevalence due to the aging population. With this growing number across the world, identifying a source of regular caregiving for people with dementia (PWD) has become a routine practice. While high income countries have formal support systems for people living with dementia and their caregivers, including adult day care and residential programs, in lower‐income countries such as Zambia, informal caregivers (often family members) assume this responsibility and serve as an interface between PWD and health services. The challenges and needs of community‐based PWD and their caregivers in Zambia have not previously been identified and understood; hence limiting the medical team’s ability to address those needs and increases the risk of negative outcomes for PWD.

Method

This was a cross sectional study (n = 33) community based people living with dementia each with a caregiver. The participants underwent a one‐time in‐depth in‐home assessment enabling collection of socio‐demographic characteristics, clinical characteristics, measurement of performance in activities of daily living and impact of supporting someone with dementia. Assessment of care needs was a based on the John Hopkins Dementia Care Needs Assessment tool. Regression analyses were conducted to identify demographic, clinical, functional and quality of life correlates of unmet needs as well as identify the independent predictors of unmet needs among PWD and their informal caregivers

Result

The mean proportion of unmet needs for patients with dementia was 57% while that of caregivers was 62%. Significantly higher unmet needs were associated with having attained a tertiary education and having an unknown type of dementia.

Conclusion

The study identified that patients with dementia and their informal caregivers had a high prevalence of unmet care needs in multiple domains. It also demonstrated that in this particular cohort, having a tertiary education and an unknown type of dementia was significantly associated with a higher proportion of unmet needs.
Long‐term effectiveness and cost‐effectiveness of collaborative dementia care: A general practitioner based randomized controlled trial
Authors: Michalowsky Bernhard , Blotenberg Iris , Platen Moritz , Kilimann Ingo , Teipel Stefan , Thyrian Jochen René , Hoffmann Wolfgang
Published: January 2025

Background

Previous trials reported that collaborative Dementia Care Management (cDCM) could be effective for patients and caregivers and cost‐effective for healthcare systems in the short term. However, long‐term evidence is lacking. Therefore, the study’s objective was to determine the long‐term efficacy and cost‐effectiveness of cDCM compared with usual care.

Method

A General Practitioner (GP)‐based, cluster‐randomized‐controlled intervention trial (DelpHi‐MV) was conducted. Participating GP practices were randomly allocated to one of two arms (care as usual or cDCM). Participants of the intervention group received a comprehensive needs assessment and individualized interventions by nurses specifically qualified for dementia collaborating with GPs and healthcare stakeholders over six months. Controls received usual care. Primary endpoints were behavioral and psychological symptoms (NPI), caregiver burden (Berlin Inventory of Caregivers' Burden), Health‐Related Quality of Life (HRQoL, QoL‐AD, SF‐12), anti‐dementia drug treatment, potentially inappropriate medication, and cost‐effectiveness (incremental cost and Quality‐adjusted Life Years, QALYs) after 36 months.

Result

308 participants (n = 221 cDCM, n = 87 usual care) were included for the efficacy analyses, and 428 (n = 303 cDCM, n = 125 usual care) for the cost‐effectiveness analysis that included deceased patients. Based on multivariate regression models adjusted for baseline scores, participants receiving cDCM showed significantly less behavioural and psychological symptoms (adjusted mean difference ‐10.3 [95% CI ‐16.9 to ‐3.6], p = 0.003, Cohens‐d = ‐0.78), better mental health (+2.26 [0.3 to 4.2], p = 0.023, d = 0.26) and lower caregiver burden (‐0.59 [‐0.8 to ‐0.4], p<0.001, d = 0.71), and more likely received anti‐dementia drugs (adjusted odds ratio 1.91 [1.0 to 3.8], p = 0.065, Cramérs‐V = 0.12) compared to usual care participants. There was no effect on overall HRQoL, physical health, or potentially inappropriate medication after 36 months. cDCM gained QALYs (+0.14 [0.01 to 0.27], p = 0.050, d = 0.20) and increased costs (+437€ [‐5,438 to 6,313], p = 0.868, d = 0.02), resulting in a cost‐effectiveness‐ratio of 3,186€/QALY. Cost‐effectiveness was significantly better in PlwD living alone (‐3,815€, +0.224 QALYs, cDCM dominates) compared to those living with a caregiver (+3.283€, +0.079 QALYs, 47,538€/QALY).

Conclusion

cDCM is effective and cost‐effective in the long term, improving patients, caregivers, and health system‐relevant outcomes beyond the intervention or short‐term periods, and, therefore, should become a health policy priority and translated into routine care practice.
Longitudinal evolution of brain hypometabolism patterns in autopsy‐confirmed AD and LATE
Authors: Labrador‐Espinosa Miguel , Silva‐Rodríguez Jesús , Moscoso Alexis , Sanchez‐Juan Pascual , Schöll Michael , Grothe Michel J.
Published: January 2025

Background

Limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) can underlie clinical presentations mimicking Alzheimer's disease (AD). Recent imaging‐pathological studies have shown that LATE associates with a specific temporo‐limbic FDG‐PET signature that differs from the typical temporo‐parietal pattern of hypometabolism in AD and may be of clinical utility for differential dementia diagnosis. Little is known about the temporal evolution of the respective hypometabolic patterns from early disease stages. We investigated the temporal evolution of LATE‐ and AD‐specific hypometabolism patterns using longitudinal ante‐mortem FDG‐PET data from autopsy‐confirmed cases.

Method

Serial ante‐mortem FDG‐PET scans acquired in an interval of ‐11 to 0 years before death (mean: ‐4.8±2.9 years; median of 3 scans/subject) were analysed from 30 autopsy‐confirmed AD patients and 10 LATE patients enrolled in ADNI. FDG‐PET images were spatially normalized to MNI space and standard uptake value ratios (pons reference) were calculated across 52 brain regions defined in the Harvard‐Oxford atlas. Region‐wise z‐scores were calculated to quantify hypometabolism relative to a healthy elderly control group (N=179). Group‐wise longitudinal metabolic decline of brain regions was calculated using linear mixed‐effects models. Predicted z‐scores were estimated in 2‐year steps over a 10‐year interval from the time of death and referenced to approximate onset of first memory problems. In addition, we evaluated the longitudinal evolution of the inferior‐to‐medial temporal ratio (IMTr) as a previously proposed differential diagnostic imaging marker.

Result

In AD, first pronounced hypometabolism (z>1) was observed in the posterior cingulate cortex and precuneus, approximately 6 years before death (5.5±4.5 years after estimated symptom onset) and progressively affecting additional temporal and lateral parietal brain regions (Fig‐1a). By contrast, first hypometabolism in LATE was observed in the hippocampus/parahippocampal cortex as early as 10 years before death, coinciding with the estimated onset of cognitive symptoms (0.1±3.3 years) and progressively including anterior temporal, subcallosal, and frontal brain regions (Fig‐1b). Interestingly, the IMT ratio showed a constant difference between AD and LATE patients across the entire observation period, including earliest disease stages (t=3.04, p=0.005)(Figure 2).

Conclusion

LATE and AD show markedly different origins and temporal trajectories of regional brain hypometabolism, indicating that FDG‐PET may differentiate between these pathologies even at early disease stages.
Efficacy and safety of DL‐3‐n‐butylphthalide in patients with mild cognitive impairment: a multicentre, randomized, double‐blind, placebo‐controlled trial
Authors: Wang Pin , Sun Wenxian , Gong Jin , Han Xiaodong , Xu Chang , Chen Yufei , Yang Yuting , Luan Heya , Li Shaoqi , Li Ruina , Wen Boye , Lv Sirong , Wei Cuibai
Published: January 2025

Background

The DL‐3‐n‐butylphthalide (NBP), a multi‐target neuroprotective drug, improving cognitive impairment in patient with vascular cognitive impairment has been confirmed. The efficacy of NBP in patients with cognitive impairment due to Alzheimer’s disease (AD) remains unknown. This study aimed to evaluate the efficacy and safety of NBP in patients with mild cognitive impairment (MCI) due to AD though a clinical randomized controlled trail.

Method

This is a 12‐month, randomized, double‐blind, placebo‐controlled, multicentric trial. The trial included patients 50 to 85 years of age who had MCI due to AD, with a clinical dementia rating (CDR) score 0.5 and a mini‐mental state examination (MMSE) score 20‐26. Subjects were randomly assigned to receive either NBP soft capsule (200mg, three times a day), or equivalent dose of placebo for up to 12 months with an allocation ratio of 1:1. The primary endpoint is the change in 12‐item Alzheimer’s disease assessment scale‐cognitive subscale (ADAS‐cog12; range, from 0 to 75, with lower scores indicating lesser severity) after 12 months. Secondary outcomes included the change in scores on the MMSE, the Sum of Boxes of CDR (CDR‐SB), Activities of Daily Living (ADL), Neuropsychiatric inventory (NPI), Auditory Verbal Learning Test (AVLT), Trail Making Test (TMT), Digit Span, as well as the standardized uptake ratio (SUVR) on FDG‐PET. All patients were monitored for adverse events (AEs).

Result

A total of 270 patients were enrolled, with 135 assigned to receive NBP soft capsule and 135 to receive placebo. The mean ADAS‐cog score at baseline was approximately 12 in both groups. The change from baseline in the ADAS‐cog score at 12 months was ‐1.30 with NBP and 0.73 with placebo (difference, ‐2.04 95% confidence interval [CI], ‐2.92 to ‐1.16; P = 0.0001). Other mean differences between the two groups in the change from baseline favoring BNP were Immediate Recall score, 1.53, (95% CI, 0.47 to 2.59; P = 0.0111). NBP‐related AE were uncommon and primarily consisted of liver dysfunction and nausea symptoms.

Conclusion

The results of the 12‐month treatment period showed that NBP was effective in improving cognitive function in patients with MCI due to AD and exhibited good safety.
Protocol for Integrating Memory Workshops into the timely detection of Alzheimer’s Disease associated with prevention, awareness and action on risk factors
Authors: Filho Otelo Corrêa dos Santos , Dunley Glaucia , França Lucia
Published: January 2025

Background

The use of blood biomarkers predictive of the presence of amyloid Aβ and ApoE4 is an effective tool to facilitate a timely AD diagnosis. About a third of dementia cases can be attributed to potentially modifiable risk factors, and the incidence of the disease can be reduced by addressing these factors. Memory Workshops integrated with early detection and actions on risk factors is an operational strategy that is both therapeutic and preventive.

Method

Memory Workshops and Timely Detection of Alzheimer’s Disease and Control of Risk Factors ‐ Memory Workshops will be held for elderly, with two components: Guided Autobiography (GAB), a life review technique, which provides the rescue, search and reinforcement of individual purposes, in a historical and sociocultural scenario common to the group, reviving and valuing the main aspects of the history of life aiming to develop new projects and the Popular Memory Collective based on psychoanalysis, which should address central themes such as significant losses, sexuality, melancholy, differentiating physiological needs, deficiencies, fears of death and illness. Elderly with cognitive complaints will be invited to undergo: 1 ‐ Collection of biomarkers for AD, with defined exclusion criteria. 2 – Recording and monitoring the evolution of risk factors for AD. Elderly people will also receive informative material about AD.

Result

It is a protocol to be implemented from February 2024 in a partnership between the Human Aging Center of the State University of Rio de Janeiro and the Intergenerational State Secretariat for Youth and Human Aging of the State of Rio de Janeiro – Brazil – Memory workshops, timely detection strategies and management of risk factors will be carried out through appropriate training by health professionals from the Project 60+ Centers of the Secretariat of State in agreement with the State University of Rio de Janeiro. 100 Centers will be created in the State of Rio de Janeiro with an estimated care of 100 elderly people per Center. Training and coordination of the work will be carried out by the authors of this abstract

Conclusion

It is a protocol to be implemented.
Discrimination of Alzheimer’s disease and non‐Alzheimer’s disease neurocognitive‐disordered patients by assessing CSF biomarkers in Thai population
Authors: Nanthasi Witsarut , Rattanabannakit Chatchawan , Wongkom Natthamon , Dujada Pathitta , Raksthaput Atthapon , Chaichanettee Sunisa , Phoyoo Paphawadee , Wachirutmangur Lertchai , Senanarong Vorapun
Published: January 2025

Background

CSF biomarkers including β‐amyloid (Aβ) (1‐42), phosphorylated tau (p‐tau) 181 and total tau (t‐tau) are used as ante‐mortem biomarkers to detect Alzheimer’s disease (AD) pathology in cognitively impaired patients. Decreased level of Aβ(1‐42), elevated level of p‐tau 181 and t‐tau are well established in AD. Base on CSF analysis technique and population, cut‐points are varied to distinguish between AD and non‐AD neurocognitive‐disordered patients. This study aimed to evaluate the local cut‐points of CSF biomarkers as diagnostic tools to discriminate AD and non‐AD neurocognitive‐disordered patients in Thai population.

Methods

We enrolled 74 cognitively impaired patients in memory clinic at Siriraj hospital, Thailand. Participants underwent a standardized diagnostic dementia evaluation, including medical history, physical examination, neuropsychological tests using Thai Mental State Examination (TMSE), Montreal Cognitive Assessment (MoCA) and Clinical Dementia Rating Sum of Boxes score (CDR‐SB), and brain imaging. Patients were clinically diagnosed with each subtype of neurocognitive disorder without knowledge of CSF biomarker results. CSF Aβ(1‐42), p‐tau 181 and t‐tau were measure by ELISA technique. Youden index–based cut‐points of CSF biomarkers were defined using receiver operating characteristic (ROC) to distinguish between AD and non‐AD neurocognitive‐disordered patients.

Results

45 (60.8%) patients were diagnosed with AD dementia and 29 (39.2%) patients were diagnosed with non‐AD neurocognitive disorders. Median values of CSF Aβ(1‐42) were significantly lower in AD group than in non‐AD group (371.0 vs. 666.0 pg/mL, p <0.001*). Median values of CSF p‐tau 181 and ratios of CSF p‐tau 181/Aβ(1‐42) were also significantly higher in AD group than in non‐AD group (p‐tau 181; 70.0 vs. 44.0 pg/mL, p = 0.002*) (p‐tau 181/Aβ(1‐42) ratio; 0.180 vs. 0.059, p <0.001*). Whereas t‐tau levels were not statistically different between groups (359.0 vs. 227.0 pg/mL, p = 0.053). Local cut‐points of CSF biomarkers to determine AD dementia were proposed as CSF Aβ(1‐42) ≤538 pg/mL (AUC 0.96, p <0.001*), CSF p‐tau 181 >56 pg/mL (AUC 0.72, p <0.001*) and p‐tau 181/Aβ(1‐42) ratio >0.094 (AUC 0.90, p <0.001*).

Conclusion

The utility of CSF Aβ(1‐42) and p‐tau 181/Aβ(1‐42) ratio was notably higher in effectively distinguishing Alzheimer's disease from non‐Alzheimer's disease neurocognitive disorder within Thai population.
Do patients with early‐stage cognitive impairment have an increased risk for developing frailty syndrome? A cross‐sectional study
Authors: Lopes Pedro de Castro , Machado João Carlos Barbosa , Barbosa Maira Tonidandel , Aguiar Bianca Pessoa , de Souza Júlia Caroline Barbosa , Ferreira João Pedro Neres Antunes , Garcia Luana Rodrigues , Leopoldino Amanda Aparecida Oliveira
Published: January 2025

Background

Frailty syndrome is a prevalent condition associated with high‐impact outcomes for the elderly, such as falls, hospitalization, functional loss and mortality. It can be triggered by several clinical conditions and dementia is one of them. More studies are needed to deeply understand the relationship between these two conditions. Frailty is prevalent in patients with advanced dementia, but this study was developed with the objective to understand if patients with mild cognitive impairment have increased risk for developing frailty too.

Method

This is a cross‐sectional study in which 87 community‐dwelling elderly people were included and evaluated in relation to the presence of cognitive impairment and frailty. Patients with severe cognitive impairment, assessed by a score less than 6 in the CS‐10 (Point Cognitive Screening) were excluded. Individuals with a score between 6 and 7 on the CS‐ 10 were considered to have mild or moderate cognitive impairment and participants with a score greater than 7 on this test were considered to have no cognitive impairment. The individuals were evaluated for the presence of frailty based on the criteria proposed by Fried. Individuals with a score greater than or equal to 3 were considered frail, with score between 0 and 2 were considered non‐frail. In order to evaluate the correlation and association between the characteristics, Pearson’s chi‐square test was calculated. If the p‐value was lower than the significance level of 0.05, it is possible to conclude the association between the development of frailty and a worse score in CS‐10.

Result

In this sample, 50.6% were frail. The mean score of the patients in CS 10 was 8.2. 69.2% of frail patients had a CS10 score between 6 and 7 points. At the highest score range above 10 points, we have that 72% are from non‐frail patients. Thus, there is an association between the risk of frailty and the CS10 score (p‐value 0.008). The Kruskal Wallis test, which evaluates the difference between the medians, also indicates statistically significant association between them (p‐value 0.002).

Conclusion

Patients with mild cognitive impairment have an increased risk of developing frailty syndrome.
Dysphagia in primary progressive aphasia: clinical predictors and neuroanatomical basis
Authors: Mazzeo Salvatore , Mulroy Eoin , Jiang Jessica , Lassi Michael , Johnson Jeremy , Hardy Chris JD , Rohrer Jonathan D. , Warren Jason D , Volkmer Anna
Published: January 2025

Background

Dysphagia is an important feature of neurodegenerative diseases and potentially life‐threatening in primary progressive aphasia (PPA), but remains poorly characterised in these syndromes. We hypothesised that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features and associated with atrophy affecting regions implicated in swallowing control.

Methods

In a retrospective case‐control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant (sv)PPA, 13 logopenic variant (lv)PPA). Using a proforma based on caregiver surveys and clinical records we documented dysphagia (present/absent) and associated, potentially predictive clinical, cognitive and behavioural features. These were used to train a machine learning model. Patients’ brain MRI scans were assessed using voxel‐based morphometry and region‐of‐interest analyses comparing differential atrophy profiles associated with dysphagia presence/absence.

Results

Dysphagia was significantly more prevalent in nfvPPA (43% vs 5% svPPA and no lvPPA). The machine learning model revealed a hierarchy of features predicting dysphagia in the nfvPPA group, with excellent classification accuracy (90.5% [95% confidence interval 77.9:100]): the strongest predictor was orofacial apraxia, followed by older age, parkinsonism, more severe behavioural disturbance and more severe cognitive impairment. Significant grey matter atrophy correlates of dysphagia in nfvPPA were identified in left middle frontal, right superior frontal and right supramarginal gyri, and right caudate.

Conclusion

Dysphagia is a common feature of nfvPPA, linked to underlying cortico‐subcortical network dysfunction. Clinicians should anticipate this symptom particularly in the context of other motor features and more severe disease.
Detecting amyloid positivity from MRI scans using comprehensible convolutional neural networks
Authors: Levin Fedor , Li Qingyue , Singh Devesh , Buerger Katharina , Fliessbach Klaus , Heneka Michael T. , Kleineidam Luca , Laske Christoph , Perneczky Robert , Peters Oliver , Priller Josef , Ramirez Alfredo , Schneider Anja , Spottke Annika , Wagner Michael , Wiltfang Jens , Düzel Emrah , Jessen Frank , Teipel Stefan , Dyrba Martin ,   the DELCODE Study Group
Published: January 2025

Background

Analysis of neuroimaging data based on convolutional neural networks (CNNs) can improve detection of clinically relevant characteristics of patients with Alzheimer’s disease (AD). Previously, our group developed a CNN‐based approach for detecting AD via magnetic resonance imaging (MRI) scans and for identifying features that are relevant to the decision of the network. In the current study, we aimed to evaluate the potential utility of applying this approach to MRI scans to assist in the identification of individuals at high risk for amyloid positivity to aid in the selection of study samples and case finding for treatment.

Method

In the current analysis, we have trained a CNN to detect amyloid positivity using MRI scans from 1461 Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants (498 cognitively normal participants, 103 participants with significant memory concern, 640 participants with mild cognitive impairment, and 220 participants with AD dementia). Amyloid positivity was assessed via amyloid PET scans obtained with [18F]florbetapir or [18F]florbetaben and quantified on a Centiloid scale. A threshold of 24.1 CL categorized 46% of participants as amyloid‐positive. The modeling approach was evaluated using 10‐fold cross‐validation, the number of epochs in training was set to 10.

Result

For each of 10 cross‐validation folds, we selected a model state corresponding to an epoch showing best performance in the validation partition. Balanced accuracy across these models ranged from 0.62 to 0.72 with an average of 0.68 (SD = 0.03).

Conclusion

We used a previously established approach to train CNNs for detecting amyloid positivity using MRI scans. Such models, particularly when tuned to have low rates of false negatives, have a potential to enhance identification of patients who would benefit from more in‐depth assessments, which could then inform antibody treatment. We are conducting ongoing work to improve and characterize the modeling approach, including evaluation of relevance maps which indicate importance of brain regions for detecting amyloid positivity. Future work will evaluate the role of amyloid positivity threshold selection. Planned analyses also include validation in independent data such as the German DZNE ‐ Longitudinal Cognitive Impairment and Dementia Study (DELCODE) dataset.
Association between digital biomarkers and anxiety: a systematic review and meta‐analysis
Authors: Lau Yolanda , Chemas Natalia , Gokani Heema Ajeet , Morrell Rachel , Walker Zuzana , Demnitz‐King Harriet , Marchant Natalie L
Published: January 2025

Background

Anxiety, both generalised anxiety disorder and anxiety symptoms, has been recognised as a risk factor and prodromal symptom of dementia. Digital biomarkers are gaining interest as proxy markers for mental health because they enable passive and continuous data collection, allowing for early detection. However, the association between digital biomarkers and anxiety remains unknown. This systematic review and meta‐analysis aimed to examine the association between digital biomarkers obtained from wrist‐worn wearables and anxiety symptoms in adults.

Method

Systematic literature searches were conducted across six databases, including unpublished grey literature. Studies investigating the association between digital biomarkers from wrist‐worn wearables and anxiety were eligible for this review. Effect sizes were combined across studies, for each digital biomarker separately, using random‐effects meta‐analyses whenever possible. Sensitivity analyses were performed to assess whether results differed according to anxiety type (state, trait), age group (young, middle, older), and sex.

Result

Twenty‐two articles were eligible. Meta‐analyses were conducted for four sleep metrics: sleep efficiency, wake after sleep onset, total sleep time, and sleep onset latency. Analyses revealed that sleep efficiency (8 studies, Fisher’s z = ‐0.08, 95% confidence interval [CI] = ‐0.15 to ‐0.01, p = 0.0263) and wake after sleep onset (6 studies, Fisher’s z = 0.13, 95% CI = 0.01 to 0.24, p = 0.0291) were associated with anxiety symptoms. In sensitivity analyses, associations persisted older adults (for sleep efficiency only) and trait anxiety. Meta‐analyses could not be conducted for physical activity metrics, however, a qualitative synthesis of the limited number of studies (five studies) revealed inconsistent results.

Conclusion

Worse sleep efficiency and longer wake after sleep onset were associated with greater anxiety symptoms. However, due to the limited number of studies, the association with physical activity remains unclear, warranting further research. Further, it became apparent that machine learning studies in this area are limited and of variable quality. Given anxiety is a prodromal symptom of dementia, future research focusing on older adults is essential to explore the use of digital biomarkers in the context of dementia risk.