bluuebunny/crossref_metadata_2025 huggingface dataset:
Related amyloid burden and cortical atrophy in individuals with subtle cognitive decline
Authors: Cersonsky Tess E.K. , Brick Leslie Ann D
Published: June 2023

Background

Subtle cognitive decline represents a stage of subclinical cognitive deterioration in which pathological biomarkers, particularly for Alzheimer’s disease may be present, including early cortical atrophy and amyloid deposition. Using individual items from the Montreal Cognitive Assessment (MoCA) and k‐modes cluster analysis, we previously identified three distinct cognitive clusters of individuals without overt cognitive impairment, which comprised a High Performing cluster (no deficits in performance), a Memory Deficits cluster (lower memory performance), and a Compound Deficits cluster (lower memory and executive function performance). In this study, we sought to understand the different relationships found in our clusters between cortical atrophy on MRI and B‐amyloid burden on PET.

Methods

Data was derived from the Alzheimer’s Disease Neuroimaging Initiative and comprised individuals with Clinical Dementia Rating of 0 with available MRI and 18‐Florbetapir B‐amyloid PET data (n = 272). Using multiple group structural equation modeling, we regressed amyloid standardized uptake value ratio (PET) on volumetric regions (MRI). Models were constrained to test significance of associations across groups defined by cognitive clusters.

Results

In our Compound Deficits cluster, greater whole cerebral B‐amyloid burden was significantly related to atrophy of the right entorhinal cortex and left hippocampus, with regression coefficients of ‐0.412 (p = 0.005) and ‐0.304 (p = 0.049), respectively. Within this cluster, right entorhinal cortical atrophy was significantly related to greater amyloid burden within multiple frontal lobe regions.

Conclusions

The Compound Deficits cluster, which represents a group at higher risk of decline with deficits in both memory and executive function, was observed to have significantly more cortical atrophy, particularly within the entorhinal cortex and hippocampus, associated with whole brain and frontal lobe B‐amyloid burden. These findings, which are consistent with the neuropsychological deficits observed on the MoCA in this cluster, point to a pattern of early pathological deterioration that may place these individuals at risk for future decline.
Psychometric properties of the Yonsei Lifestyle Profile‐BREF of community‐dwelling older adults
Authors: Park Kang‐Hyun , Park Ji‐Hyuk , Hong Ickpyo , Nam Sanghun
Published: June 2023

Background

Lifestyle is important indicator of health and well‐being among older adults. Therefore it is important to measure the individual’s lifestyles effectively. This study aimed to examine the validity and reliability of the Yonsei Lifestyle Profile‐BREF (YLP‐BREF).

Method

In total, 569 community‐dwelling older adults were recruited via an online survey. Confirmatory factor analysis of a one‐factor model was conducted for each of the three domainsof the YLP‐BREF. The total score of YLP‐BREF and each domain were evaluated for convergent validity and divergent validity using the WHO quality of life scale and center for epidemiologic studies depression scale. Additionally, Cronbach’s alpha reliability was examined. Finally, an optimal cutoff score for the YLP‐BREF was established using receiver operating characteristic curve analysis.

Result

The five items of physical activity demonstrated an acceptable fit (CFI = 0.962; TLI = 0.923; RMSEA = 0.095; SRMSR = 0.033). The four items of activity participation illustrated an acceptable fit except for the Tucker–Lewis index (CFI = 0.959, TLI = 0.876, RMSEA = 0.080, SRMSR = 0.022). All 13 nutrition items showed an acceptable fit fit (CFI = 0.927; TLI = 0.913; RMSEA = 0.076; SRMSR = 0.047). Cronbach’s alpha reliability was good for nutrition (r = 0.85) and acceptable for physical activity (r = 0.61), but insufficient for activity participation (r = 0.43). Convergent and divergent validities were good (r = 0.17–0.32, p<0.001; r = 0.01—0.10, p<0.001). The optimal cut‐off score for the YLP‐BREF was 9 for physical activity, 6 for activity participation, and 28 for nutrition

Conclusion

The YLP‐BREF is a reliable and valid self‐report questionnaire for measuring multifaceted lifestyle factors in community‐dwelling older adults in South Korea.
The impact of social network characteristics on health among community‐dwelling elderly in South Korea: Application of social network analysis
Authors: Park Kang‐Hyun , Jeon Byoung‐Jin
Published: June 2023

Background

Older adults’ social network is associated with health and quality of life. This study examines the association between characteristics of social network (friendship network) and subjective well‐being of community‐dwelling older adults.

Method

This study was conducted between June 2015 to August 2015, with a total of 146 respondents. The contracture and density of the social network was analysed by using social network analysis. Additionally, in order to investigate the impact of social network on health, multiple liner regression analysis was used through Netminer 4.0 version. P values of less than 0.05 were considered to indicate statistical significance.

Result

The higher the out‐degree (376.161) and the in‐closeness (201.825), the better the health. On the other hand, the higher the in‐degree (‐279.167) and the out‐closeness (‐52.620), the poor the health. the higher the out‐degree (218.747) and the in‐closeness (170.075), the better the health. In addition, it was showed that religion had a negative effect on health, and the older adults with high level of education illustrated better health.

Conclusion

The findings suggest that the higher out‐degree and in‐closeness intensity affect the health of older adults positively, but the higher the in‐degree and out‐closeness intensity affect the health negatively. Therefore, health professionals should use appropriate strategies to increase the strength of social networks in order to improve the health of the elderly living in the community.
Associations between dietary patterns and structural neuroimaging markers of relevance for dementia
Authors: Samuelsson Jessica , Marseglia Anna , Lindberg Olof , Westman Eric , Kern Silke , Ahlner Felicia , Rothenberg Elisabet , Skoog Ingmar , Zettergren Anna
Published: June 2023

Background

Diet is a lifestyle factors that could influence the risk of developing dementia. However, the impact of diet on the brain is not fully understood. Investigating associations between dietary patterns and neuroimaging markers of relevance for dementia could potentially increase this understanding.

Method

This study includes cross‐sectional data from the population‐based Gothenburg H70 Birth Cohort Studies, Sweden, including 610 dementia‐free 70‐year‐olds (born 1944, examined 2014‐16) with dietary and magnetic resonance imaging (MRI) data (54% women). Three dietary patterns were derived with principal component analysis, a western‐like pattern (e.g., refined cereal products, sweets, savory bakery/fast food), a Mediterranean‐like pattern (e.g., vegetables, fruits, whole grain cereal products) and a low‐fiber and high‐alcohol pattern (e.g., red meat/processed red meat, eggs, alcoholic beverages). Brain MRI markers were of overall neurodegeneration (i.e., mean cortical thickness), Alzheimer’s disease (AD) neurodegeneration (based on cortical thickness of AD‐signature areas), and vascular brain pathology including early abnormalities in the white matter microstructure (derived from diffusion tensor imaging) and small vessel disease (presence of white matter hyperintensities, lacunes, cerebral microbleeds, and/or perivascular spaces). In data analysis, linear and ordinal regression models were adjusted for sex, energy intake, educational level, physical activity level, smoking and body mass index.

Result

Results from this study showed a positive association between higher adherence to the Mediterranean‐like dietary pattern and higher white matter microstructural integrity (B 0.077; 95% CI 0.002 – 0.153). Moreover, a higher adherence to the low‐fibre and high‐alcohol dietary pattern was negatively associated with total mean cortical thickness (B ‐0.011; 95% CI ‐0.019 – ‐0.003) and an AD signature of cortical thickness (mean entorhinal, inferior temporal, middle temporal, and fusiform thickness) (B ‐0.013; 95% CI ‐0.024 – ‐0.001) in the fully adjusted models. No associations were found between the dietary patterns and the small vessel disease markers. Nor were there any associations between the western‐like dietary pattern and the MRI markers.

Conclusion

This study suggests that there may be an association between certain dietary patterns and dementia‐related alterations. These findings could be of importance for dementia prevention strategies and for future intervention studies investigating the effect of dietary patterns in relation to dementia.
High lifelong cognitive reserve prolongs disability‐free survival: Role of cognitive function
Authors: Li Xuerui , Yang Wenzhe , Wang Jiao , Dove Abigail , Qi Xiuying , Bennett David A , Xu Weili
Published: June 2023

Background

High cognitive reserve (CR) has been related to a decreased dementia risk, but the association between CR and survival with independence is unknown. We examined whether lifelong CR accumulation is associated with disability‐free survival and explored the extent to which cognitive function mediates this association.

Method

Within the Rush Memory and Aging Project, 1,633 dementia‐ and disability‐free participants (mean age: 79.3 years) were followed annually for up to 22 years to detect disability and deaths. A lifelong CR indicator was derived based on information about education, early‐life, mid‐life, and late‐life cognitive activities, and late‐life social activity, and categorized into tertiles (low, moderate, and high). Disability was assessed annually in terms of participants’ ability to conduct activities of daily living and survival status was observed during the follow‐up period. Global cognitive function was assessed annually with a battery of 19 tests. Data were analyzed using Cox models, Laplace regression, and generalized structural equation models.

Result

During the follow‐up (median: 4.35 years, interquartile range: 2.01 to 7.98 years), 1,079 (64.6%) participants died or developed disability. In multi‐adjusted Cox models, CR score was does‐dependently associated with disability/death (hazard ratio [HR] 0.96, confidence interval [CI] 0.93–0.99). Compared to low CR, the multi‐adjusted HR (95% CI) of high CR was 0.82 (0.70–0.95) for disability/death. In Laplace regression, the median disability‐free survival time was prolonged by 0.17 (95% CI 0.05–0.30) years per unit higher CR score, and 0.99 (95% CI 0.28–1.71) years for participants with high CR compared to low CR. In mediation analysis, cognitive function mediated 35.7% of the association between CR and disability‐free survival.

Conclusion

High lifelong CR is associated with prolonged disability‐free survival, and cognitive function mediates about one‐third of this association.
Incidence rate ratios of motorcycle crash‐related hospitalizations within 1 year of dementia diagnosis in younger adults: A nationwide population‐based study in Taiwan
Authors: Liu Chih‐Ching
Published: June 2023

Background

The cognitive impairment and motor deficiency due to dementia may adversely affect the ability and skill related to ride motorcycle. However, little information regarding the incidence and risk of motorcycle crash‐related hospitalizations among patients with dementia. This study estimates the incidence rate ratios (IRR) of motorcycle crash‐related hospitalizations between first‐diagnosed dementia and non‐dementia.

Method

In this retrospective population‐based cohort study, we compared dementia aged 40‐64 years and its age‐ and sex‐ matched subjects without dementia from the Taiwan National Health Insurance Research Database entries and Taiwan Police‐reported Traffic Accident Registry between 2006 and 2015. The incidence of motorcycle crash‐related hospitalizations was compared between first‐diagnosed dementia and non‐dementia cases using IRR, stratified by age, sex, and charlson index. The incidence densities of motorcycle crash‐related hospitalizations were estimated based on Poisson assumption.

Result

Over 1‐year of follow‐up, the incidence densities of motorcycle crash‐related hospitalizations were 29.73 and 10.46 per 10,000 person‐years for subjects with and without dementia, respectively, with an IRR of 2.84 (95% CI 1.99 to 4.06). Regardless of any age, sex or charlson index, the incidence densities of motorcycle crash‐related hospitalizations were higher in patients with dementia than subjects without dementia, with the IRR ranging from 1.07 (95% CI 0.49 to 2.37) to 7.06 (95% CI 2.48 to 20.14). Unlike subjects without dementia, the incidence density of motorcycle crash‐related hospitalizations decreased with age among patients with dementia. Among them, the highest IRR was 7.06 (95% CI 2.48 to 20.14) in those aged 40‐44. In gender group, the IRR of motorcycle crash‐related hospitalizations were higher in male (3.34, 95% CI 2.07 to 5.38) than in female (2.27, 95% CI 1.32 to 3.89). The effect of dementia on incidence rate of motorcycle crash‐related hospitalizations were highest in those without comorbidities (IRR 4.17, 95% CI 2.74 to 6.36).

Conclusion

Younger adults with dementia may rise the risk of motorcycle crash‐related hospitalizations within 1 year after diagnosis compared to those without dementia, which suggests the reinforcement transport safety in younger adults with dementia is needed.
Association of pulmonary function with mild cognitive impairment, its progression to dementia and brain pathologies: A community‐based cohort study
Authors: Wang Jiao , Dove Abigail , Song Ruixue , Qi Xiuying , Ma Jun , Bennett David A , Xu Weili
Published: June 2023

Background

The association of pulmonary function (PF) with mild cognitive impairment (MCI) and its underlying mechanisms remain unclear. We examined the association of PF with MCI and its progression to dementia, and brain pathologies.

Method

Within the Rush Memory and Aging Project, the 1,312 dementia‐free participants (mean age: 79.41±7.77 years) included a cognitively intact group (n = 985) and an MCI group (n = 327). The two groups were followed for up to 21 years to detect incident MCI and dementia. PF was assessed with a composite score based on forced vital capacity, forced expiratory volume in 1s, and peak expiratory flow measured at baseline, and further divided into tertiles (i.e., lowest, middle, and highest). MCI and dementia were diagnosed following standard criteria. During the follow‐up, 540 participants died and underwent autopsies for neuropathological assessment (including Alzheimer’s disease [AD], and vascular brain pathologies). Data were analyzed using Cox regression, Laplace regression, and logistic regression.

Result

During the follow‐up (median 7 years, interquartile range 4‐10 years), 461 participants developed MCI in the cognitively intact group, and 324 had dementia among participants with MCI. Compared to the highest PF, the multi‐adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were 1.95 (1.43‐2.66) for MCI in the cognitively intact group, and 1.55 (1.03‐2.33) for dementia in the MCI group, respectively. The median time from MCI to dementia development was 2.75 (95% CI: 2.15‐3.34) years shorter in people with the lowest PF than those with the highest PF. In the pathological data analysis, the lowest PF was significantly related to higher AD pathology (odds ratio [OR]: 1.32, 95% CI 1.19‐1.47) and vascular brain pathologies (OR: 3.05, 95% CI 1.49‐6.25) compared to the highest PF.

Conclusion

The lowest PF is associated with nearly 2‐fold risk of MCI and accelerates progression from MCI to dementia by almost 3 years. Both neurodegenerative and vascular mechanisms may underlie this association.
Tau influences the severity of delusions in older persons with early‐stage cognitive decline
Authors: Khoury Marc A , Bahsoun Mohamad‐Ali , Fahdel Ayad , Shunbuli Shukrullah , Venkatesh Saanika , Ghazvanchachi Abdollah , Mitha Samir , Chan Karissa , Fornazzari Luis R , Churchill Nathan W , Ismail Zahinoor , Munoz David G. , Schweizer Tom A. , Moody Alan R. , Fischer Corinne E. , Khademi April
Published: June 2023

Background

The relationship between delusional severity and structural brain changes in patients with cognitive decline is unclear. In prior work by our group, we conducted texture and volume analysis of Normal Appearing Brain Matter (NABM) using FLAIR MRI sequences in a cognitively impaired delusional cohort. Our results demonstrated that with more severe delusions, greater global brain disease burden and tissue degeneration in NABM is apparent. In this study we examined the relationship between our findings and neurodegenerative biomarkers, ApoE4 and plasma tau.

Methods

A total of 42 patients with Alzhiemer’s disease (AD) or Mild Cognitive Impairment (MCI) with delusions as identified by the Neuropsychiatric Inventory‐Quick version (NPI‐Q) were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). From fluid‐attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) images, Brain extraction and intensity standardization alghorthims were applied to extract the normal‐appearing brain matter (NABM). Three biomarkers were measured from the NABM region, which included volume and two texture features called integrity and damage that measure the structural integrity of tissue and tissue damage. Statistical analysis included a multivariable stepwise regression of each biomarker as a dependent variable across delusional severity groups 1 (lowest severity) to 3 (highest severity) and the inclusion of sex, age, education, ApoE4 and plasma tau as co‐variates.

Results

Data were gathered on the 42 participants representing 164 MRI scans. Significant associations were found between baseline plasma tau, delusional severity group 3 for the NABM integrity and volume biomarkers (p<.05). Additionally, ApoE4 homozygotes were signficantly associated to NABM volume, integrity and damage, though no association was found with delusional severity.

Conclusion

These findings suggest that plasma tau may be linked to both delusional severity and structural alterations within the NABM while ApoE4 status is more strongly associated with structural alterations in the NABM with no effect on delusional severity. Further longitudinal studies are required to establish plasma tau associated mechanisms of delusional severity.
One year longitudinal change of tau accumulation on [18F]PI‐2620 PET in Alzheimer spectrum
Authors: Oh Minyoung , Oh Seung Jun , Lee Sang Ju , Oh Jungsu S. , Roh Jee Hoon , Lee Jae‐Hong , Kim Jae Seung
Published: June 2023

Background

We investigated longitudinal changes in cortical tau accumulation and their association with cognitive decline in patients with Alzheimer’s disease (AD) spectrum using [18F]PI‐2620 PET.

Method

We enrolled 54 (69.9±8.5 y, M:F = 16:38) participants (8 cognitively normal [NC], 28 mild cognitive impairment [MCI], 18 AD) who completed [18F]PI‐2620 PET scans at baseline and 1 y follow up. Subject also underwent [18F]florbetaben PET (baseline only), MRI and neuropsychological tests. Aβ PET images were visually scored as positive or negative. Aβ+ MCI & AD were classified into early onset (<65 y, EO+) and late onset (≥65, LO+) group. Standardized uptake value ratios (SUVr) of [18F]PI‐2620 PET were determined by cerebral to inferior cerebellar ratio and corrected for partial volume effect. Cortical volumes were calculated from 3D T1‐weighted MR images. We also investigated a correlation between the progression of tau accumulation and cognitive decline.

Result

Thirty eight out of 57 participants showed Aβ+ (1 NC, 20 MCI, 17 AD). Global SUVr values of [18F]PI‐2620 PET were 0.96±0.07 in 7 Aβ‐ NC, 1.23±0.41 in 17 LO+ (76.7±3.8y) and 1.86±0.87 in 20 EO+ (63.4±5.4y) (p<0.001). It increased by 0.09±0.14 (7.0%) in LO+ and 0.14±0.27 (11.6%) in EO+ in contrast to no change in NC‐. EO+ showed abundant tau accumulation in Braak III‐V areas at baseline with rapid accumulation in Braak V area (0.33±0.41 [13.9%] vs. 0.08±0.14 [6.7%], p = 0.010) than LO+ group. It showed abundant and rapid accumulation on Braak 3 areas in LO+ group (1.61±0.53 at baseline, change: 0.15±0.25 [8.2%]). Deterioration of the visuospatial function and verbal memory was associated with the progression of tau accumulation in Braak III‐V areas in EO+ group. Progressive atrophy in Braak III‐V areas were associated with the progression of tau accumulation in LO+ group whereas hippocampal atrophy did in EO+ group.

Conclusion

Tau accumulation measured by [18F]PI‐2620 in EO+ showed rapid accumulation in Braak III‐V areas and correlated with deterioration of the visuospatial function and verbal memory. It suggests that [18F]PI‐2620 PET is potential biomarker for selecting therapeutic target and monitoring treatment effect for tau targeting treatment.
Leveraging natural language processing to identify social determinants of health for patients with Alzheimer’s disease and related dementias from electronic medical records
Authors: Wu Wenbo , Najarian Cyrus , Vydiswaran V. G. Vinod , Bynum Julie , Mahmoudi Elham
Published: June 2023

Background

Social determinants of health (SDoH) have a significant impact on the well‐being of individuals with Alzheimer’s disease and related dementias (ADRD). ADRD patients from socioeconomically disadvantaged groups are generally subject to higher risks of adverse health events than those from advantaged groups. However, information related to SDoH is not collected systematically in most medical institutions. Unstructured electronic medical records (EMRs), including free‐text clinical narratives and nurse and social worker notes, may include salient information that can be used to identify individuals who may need assistance. In this study, we sought to develop a rule‐based, natural language processing (NLP) algorithm that identifies from patients’ unstructured EMRs their housing instability, transportation problems, food and medication insecurity, solitariness, and financial exploitation.

Method

We randomly selected 1,000 medical notes from Michigan Medicine between 2016 and 2019 and partitioned them into 750 notes for training and 250 notes for testing. Training notes were preprocessed by a prototype algorithm and annotated by registered nurses. We then trained the algorithm by resolving all human and machine disagreements. The post‐training NLP algorithm was evaluated on the testing notes. The most promising medical notes that found information about SDoH were social worker notes.

Result

The NLP algorithm achieved 85.3% of note‐wise accuracy. Determinant‐wise accuracy scores were 88.6% (housing), 91.1% (transportation), 86.7% (food), 92.0% (medication), 87.4% (solitariness) and 95.3% (financial exploitation). Determinant‐wise F1‐scores were 90.6% (housing), 86.9% (transportation), 91.3% (food), 95.7% (medication), 82.3% (solitariness) and 93.8% (financial exploitation).

Conclusion

Our NLP algorithm is a stand‐alone module that can run on real‐time EMRs and extract information about SDoH with a high level of accuracy. Findings can be used by clinicians, care managers, and social workers to pragmatically and efficiently reach out to ADRD patients who may need assistance with food, transportation, or housing. In doing this, adverse health events may be reduced among this vulnerable patient population. Future efforts will focus on making this algorithm generalizable for use at other institutions.
Best practices for conducting person‐centered life story assessments for people living with dementia: A scoping review
Authors: Gholizadeh Shadi , Popolizio Elizabeth M. , Wile Michelle , Smith Erica C.
Published: June 2023

Background

There has been a growing commitment to incorporating the life stories of people with dementia as part of their person‐centered care. Although there has been some research exploring the role of life story work and reminiscence therapy on various dementia‐related outcomes, there has been relatively little scholarly work examining best practices for the incorporation of the life stories of people with dementia as part of a person‐centered assessment. The aim of this scoping review is to examine the themes and gaps associated with undertaking life history/life story assessment (LSA).

Method

Two databases (PubMed and PsychINFO) were searched from inception through October 1st, 2021 for English‐language articles and books using keywords relating to life story and dementia. The search returned 119 articles after removal of duplicates with 28 selected for inclusion into the review.

Result

Six key themes emerged, including 1) the lack of a standardized approach or best practices in LSA, 2) differing goals in LSA (e.g., the creation of a life story book for reminiscence therapy versus the collection of data to help guide carer interactions), 3) the importance of flexibility in collecting information, 4) the role of close others as collateral sources of information, 5) the potential for one’s own biases and context to influence how and what information is collected, and 6) the role of technology in facilitating LSA.

Conclusion

Incorporating LSA is an important aspect of person‐centered care for people with dementia, yet there is little guidance on how to best approach the assessment. There are gaps in understanding the administration and mechanisms of LSA and the role of LSA in guiding daily care interactions and carer impacts (e.g., self‐efficacy in caring). There is a need for tools and guidance to enable individuals with varied professional backgrounds and disparate cultural contexts to collect life stories that are inclusive and encompass the many salient identities that a person with dementia might hold.
A scoping review of social media use as a form of engagement among people with dementia
Authors: Gholizadeh Shadi , Popolizio Elizabeth M. , Wile Michelle , Smith Erica C.
Published: June 2023

Background

There are an estimated 50 million adults living with dementia worldwide, a number that is projected to triple by 2050 (Patterson, 2018). Because there is no cure for Alzheimer’s disease and other dementias, maintaining and supporting quality life are among the most important care targets. Engagement in meaningful and purposeful activities is a cornerstone of quality of life, however opportunities for participation in meaningful activities can be limited for people with dementia (Wenborn et al., 2008). Although social media has the potential to be a source of engagement and connectivity for people with dementia, there is little known about the impacts of social media use on engagement‐related outcomes in people with dementia.

Method

Two databases (PubMed and PsychINFO) were searched from 2000 through November 12st, 2021 for English‐language articles with search terms relating to dementia and social media in the title. The search returned 23 articles after removal of duplicates with 7 selected for inclusion into the review.

Result

Although there has been an increase in the scholarly exploration of using social media as a tool or raising awareness about dementia and providing a space for connection for carers, there is little research examining social media use in people with dementia. The research that does exist has primarily explored Twitter use and people with early‐onset dementia. Themes that emerged from the articles reviewed included 1) social media use as a tool to counter loss of identity, 2) social media as a forum for support following a diagnosis, 3) a need for greater accessibility, 4) the presence and lack of consideration regarding safety and privacy risks, and 5) dementia activism as a source of engagement and purpose.

Conclusion

The potential for social media to be a tool for social engagement for people living with dementia is relatively unexplored as are the considerations for safety and privacy. There is a need to more broadly understand the patterns and context of social media use among people with dementia. There are also opportunities for interventions using social media as a pathway to intergenerational and social connection, meaningful engagement, and cognitive stimulation.
Genetic prion diseases presenting as frontotemporal lobar degeneration: clinical features and diagnostic challenge
Authors: Chen Zhongyun , Wu Liyong , Chu Min , Kong Yu , Xie Kexin , Cui Yue
Published: June 2023

Background

Elucidate the clinical and ancillary feature of genetic prion diseases (gPrDs) presenting with frontotemporal lobar degeneration (FTLD) in order to aid early identification, diagnosis, and referral for genotype testing.

Method

Global data of gPrDs presenting with FTLD caused by prion protein gene (PRNP) mutations were collected from literature review and our records. Fifty‐one cases of typical FTLD and 136 of prion diseases admitted to our institution were included as controls. Clinical and ancillary data of the different groups were compared.

Result

Forty‐nine cases of gPrDs presenting with FTLD were identified, 23 of which were female. Twenty‐three mutations in PRNP have been reported to be associated with the FTLD, with P39L being the most commonly reported, seen in 4 families with 5 cases. Compared to FTLD or prion diseases, gPrDs presenting with FTLD is characterized by earlier onset age (median: 45 vs. 61/60 years) and stronger family history (81.6% vs. 27.5/13.2%). In addition, gPrDs presenting with FTLD exhibited shorter duration (median: 5 vs. 8 years), and a higher rate of clinical and ancillary features of prion diseases compared to FTLD. Compared to prion diseases, gPrDs presenting with FTLD had a longer duration of symptoms (median: 5 vs. 1.1 years), higher rates of frontotemporal atrophy (89.7% vs. 3.3%), lower rates of periodic short‐wave complexes on EEG (0% vs. 29.4%), and hyperintensity on MRI (25.0% vs. 83.0%). The frequency of the Val allele for codon 129 in PRNP carriers with FTLD was significantly higher than that reported in literature for gPrDs (33.3% vs. 19.2%).

Conclusion

GPrDs presenting with FTLD is characterized by early‐onset, strong family history, high frequency of the Val allele for codon 129 in PRNP. The clinical features of GPrDs presenting with FTLD is intermediate of the two distinct conditions, while the auxiliary features were closer to that of FTLD. Patients with these characteristics need to be considered for PRNP genotype testing.
Cerebrospinal fluid lipid signature as an indicator of risk and rate of progression from mild cognitive impairment to Alzheimer’s Disease
Authors: Dakterzada Faride , Jové Mariona , Pamplona Reinald , Piñol‐Ripoll Gerard
Published: June 2023

Background

Lipids and lipid intermediates are essential for brain functions. Lipid dysregulation and its role in Alzheimer’s Disease (AD) pathogenesis is well documented. However, little is known about the role of lipids in progression and the rate of progression from Mild Cognitive Impairment (MCI) to AD. Our objective was to determine Cerebrospinal Fluid (CSF) lipids that could be implicated in the progression or rate of progression from MCI to AD.

Method

We analyzed the CSF lipid profile of patients with MCI (N = 92) by liquid chromatography coupled with mass spectrometry. The association of lipids with progression was studied by logistic regression and a Cox regression model was used to assess lipids associated with the speed of progression from MCI to AD. We adjusted our analyses for age, sex, core CSF AD biomarkers, APOE4 status, and MMSE.

Result

Forty‐eight (53%) MCI patients progressed to AD during follow‐up (58 ± 12.5 months). Two lipids were associated with progression, of which one as a risk factor (OR 9.288, 95% CI [1.67 – 51.65], p = 0.011) and one as protector (OR 0.048, 95% CI [0.048 – 0.989], p = 0.048). Five lipids were associated with the rate of progression, of which three were associated with a shorter time to progression (OR 2.449, 99% CI [1.226 – 4.892], p = 0.011; OR 2.227, CI 99% [1.119 – 4.430], p = 0.023; and OR 2.542, 99% CI [1.184 – 5.455], p = 0.017) and two with a longer time to progression (OR 0.173, 99% CI [0.066 – 0.449], p < 0.001; and OR 0.442, CI 99% [0.231 – 0.845], p = 0.014).

Conclusion

Our results suggest that lipid dysregulation could have an important role in progression and rate of progression from MCI to AD. Our data also indicate that CSF lipid alterations could have clinical implications as biomarkers of progression and speed of progression.
Clinical validity of a borderline group in CSF biomarker classification in Alzheimer’s disease
Authors: Yosypyshyn Dariia , Costa Ana Sofia , Kučikienė Domantė , Schulz Jörg B. , Reetz Kathrin
Published: June 2023

Background

Efforts to translate the NIA‐AA AT(N) dichotomic research framework of Alzheimer’s disease (AD) into clinical practice should evaluate how to deal with borderline cases. We characterise a peri‐threshold group of individuals regarding Aß classification, using the Aß42/Aß40 ratio in cerebrospinal fluid (CSF).

Method

We conducted a retrospective study of consecutive patients referred to a university hospital memory clinic for diagnostic evaluation of cognitive impairment. We identified individuals (n = 31) with a Aß42/Aß40 ratio within a prior defined borderline zone. Two additional groups, matched for clinical severity, age and sex, were used for comparisons: a low Aß42 (normal Aß42/Aß40 ratio >0,5; pathological Aß42, n = 23), and a typical AD reference group (A+T+(N+)), n = 50). We compared demographic, clinical, neuropsychological and neuroimaging characteristics between the groups.

Results

Included patients had a median age of 72 years and presented either with mild cognitive impairment (CDR 0.5) or mild dementia (CDR 1). Groups did not differ in demographic and clinical characteristics (education, disease duration, prevalence of vascular risk factors). In comparison to the typical AD reference group, patients in the borderline group were overall similar, except for better mean performance on the MMSE (26 vs. 21, p<0.05), verbal delayed recall (mean z‐score ‐1.9±1.6 vs. ‐3.1±1.9, p<0.05) and verbal recognition (mean z‐score ‐1.65±1.1 vs. ‐2.5±1.8, p< 0.05). They also showed a less severe degree of parietal atrophy (Koedam rating score, p<0.05). Compared with the individuals in the low Aß42 group, the borderline group only had a better performance in semantic fluency (mean z‐score ‐1.3±1.9 vs. ‐2.3, p<0.05), verbal learning (mean z‐score ‐2.0±2.2 vs. ‐2.93±2.6, p<0.05) and less severe score in the medial temporal lobe atrophy rating scale (median score 1 vs. 2, p<0.001). The presence of abnormal phosho‐Tau levels did not mediate the observed differences.

Conclusion

These findings suggest that patients in the borderline group are at least partly similar to the typical AD group, as well as the low Aß42 group. Further information from longitudinal data to assess risk progression and cross‐validation in other cohorts is needed to better translation of the AT(N) classification and assist clinical decision regarding borderline cases.
Association between APOε4 allele and cognitive function in healthy Brazilians elderly from Baixada Santista
Authors: Ginsicke Danielle Cristine , Bomfim Larissa Gomes Peres , de Barros Vinícius Lucio , Souza Melyssa Alves , Zanesco Angelina , Colovati Mileny Esbravatti Stephano
Published: June 2023

Background

The faster memory decline was associated with the presence of the apolipoprotein E4 (APOε4) allele, a genetic risk factor for late‐onset Alzheimer’s disease (AD). Studies suggest that the relationship between cognitive decline and APOE ε4 allele in healthy elderly may reflect the preclinical risk to AD. This study examined the influence of apolipoprotein E4 (APOε4) genotype on the cognitive function of the older people from Baixada Santista (Brazil).

Method

This study was approved by the Ethical Committee Board from Medical School/UNIMES (Number: CAAE 20938619.4.0000.5509). Seventy‐two participants with ≥65 years old, both sexes. were eligible for the study. Cognitive function and the level of physical activity were assessed by the mini‐mental state examination (MMSE) and Baecke questionnaire for older, respectively. APOE genotyping was performed in 66 out of the 72 participants. Statistical analysis was performed by using the BioEstat version 5.0, Kolmogorov‐Smirnov test, z‐score, student t or Mann‐Whitney test was applied according to the normality. The Chi‐square test was used for comparison between the sexes. Pearson correlation was also performed. P < 0.05 was considered statistically significant.

Results

Seventy‐two older people were assessed (women = 52 and men = 20), and the mean age was 73±7 years old, Baecke score (3.74 ±3.82), MMSE (27±3), and educational status (8 ± 4 years). As expected, a positive correlation was detected between the education level and MMSE score (r = 0.359, p < 0.05). No difference was found between the sexes for age, level of physical activity, MMSE, and education status (p > 0.05). Regarding the APOE genotype, we found the following frequency ɛ2/ɛ2 (1.5%), ɛ2/ɛ3 (16.7%), ɛ2/ɛ4 (1.5%), ɛ3/ ɛ3 (59.1%), and ɛ3/ɛ4 (21.2%). No correlation was found between carriers (presence of the ɛ4 allele) and non‐carrier for the MMSE score, varying between 27 to 30.

Conclusion

Our preliminary data show that the less educational status influences the cognitive decline in the older Brazilian population. However, no differences between the sexes were observed for all parameters indicating a homogenous population. Additionally, the cognitive function score was not influenced by the presence of the APOɛ4 allele in this population.
Fine‐grained ordering of white matter degeneration in the Alzheimer’s disease pathophysiological cascade
Authors: Parker Christopher S
Published: June 2023

Background

The role of white matter (WM) neurodegeneration in Alzheimer’s disease (AD) is poorly understood. Fine‐grained sequencing of WM neurodegeneration could provide new avenues for early diagnosis and novel disease‐modifying therapies to slow or halt AD progression. Previous approaches are limited by their coarse granularity and incomplete disease coverage. In this study, we apply event‐based disease progression modelling (DPM) (Fonteijn et al, Neuroimage, 2012), which can provide fine‐grained ordering, to estimate progression of regional WM abnormality in AD.

Method

Diffusion tensor imaging (DTI) markers of WM abnormality and Freesurfer volumetric markers of grey matter (GM) atrophy were obtained from ADNI. DTI markers were hemisphere‐averaged and GM volumes were normalised by head size. Eleven WM ROIs with reported AD abnormality and 4 reference GM ROIs were selected for sequencing (abbreviations in Table 1), yielding complete data for 83 cognitively normal subjects, 40 AD patients and 102 MCI subjects. Event‐based DPM (github.com/ucl‐pond/kde_ebm) was used to estimate a data‐driven sequence of neurodegeneration and its uncertainty (positional variance), and individuals were assigned to their most likely stage (Young et al., Brain, 2014). Resampling analysis assessed the robustness of the estimated sequence.

Result

Fig. 1 shows the first data‐driven sequence of WM abnormalities in AD, including positional variance, with GM abnormality events for reference. The earliest WM events are increases in mean diffusivity (MD) in CGH and axial diffusivity (AxD) in FX and BCC. Subsequently, a cascade of AxD events in corpus callosum regions precedes abnormality in other medial temporal lobe WM structures.

Fig. 2 shows the sequence is relatively robust under resampling, with low positional variance and similar median positions for most ROIs. Subject staging (Fig. 3, 4) shows that the fine‐grained approach splits MCI subjects with hippocampal atrophy into those with hippocampal atrophy and those with additional increased MD in CGH.

Conclusion

This study finds WM microstructural abnormality among the earliest events in AD. Early hippocampal WM abnormality and corpus callosum ordering are consistent with early memory deficits in AD and inferences from cruder group‐based comparisons. The order suggests Wallerian degeneration rather than retrogenesis is the primary driver of WM neurodegeneration in AD.
MRI‐based measure of dementia risk derived using machine learning is strongly associated with measures of longevity and biological age
Authors: Casanova Ramon , Anderson Andrea , Barnard Ryan , Justice Jamie , Kucharska‐Newton Anna , Windham B Gwen , Palta Priya , Gottesman Rebecca F. , Mosley Thomas H. , Hughes Tim M. , Wagenknecht Lynne E , Kritchevsky Stephen B
Published: June 2023

Background

Machine learning and artificial intelligence methods have been applied to brain images to estimate measures of brain aging. However, only rarely have these measures been examined in the context of biologic age. Here, we investigated associations of an MRI‐based measure of dementia risk the Alzheimer’s disease pattern similarity (AD‐PS) scores with measures of longevity and biological age.

Method

Participants were those from visit 5 of the Atherosclerosis Risk in Community Study with cognitive status adjudication and MRI available. The AD‐PS score was estimated based on previously reported machine learning methods. We evaluated associations of the AD‐PS score with all‐cause mortality. Participants were stratified by AD‐PS tertiles and the analyses were adjusted for age, race, sex, hypertension and smoking. AD‐PS score was examined in association with 32 proteins reported to be associated with age. In these analyses, we used Bonferroni correction (α = 0.05,p<0.0016). Finally, associations with a deficit accumulation index(DAI) based on 38 health items was investigated. In both cases, linear regression models were adjusted for age, race and sex. Sensitivity analyses using only cognitively normal (CN) individuals were performed.

Result

Mortality – A total of 356 participants died within 8 years of follow‐up. The AD‐PS score was significantly associated(p<0.001) with time to all‐cause mortality. Participants in the lowest tertile had lower all‐cause mortality rate compared to those in the highest tertile (HR: 0.43;95% CI:0.31,0.60). The association remained significant when restricting the sample to only CN subjects (HR for lowest tertile:0.53; 95% CI:0.35,0.81, p = 0.0028).

Age related proteins ‐ The AD‐PS scores were significantly associated (p<0.05, uncorrected) with 10 of the 32 proteins. Growth/differentiation factor 15(GDF‐15) and pleiotrophin remained significant after correction for multiple‐testing. Analysis of CN participants showed a subset of the same proteins to be significant (p<0.05,uncorrected) but only the GDF‐15 remained significant after correction for multiple‐testing.

DAI ‐ A linear regression model showed a significant association between DAI and AD‐PS scores overall (coeff = 0.52; 95% CI:0.37‐0.67) and in the CN subset (coeff = 0.3,95% CI:0.13‐0.48).

Conclusion

While the AD‐PS scores were created as a measure of dementia risk, our analyses suggest that they could also be capturing brain aging.
Continuation rates of newly prescribed donepezil among patients with Alzheimer’s disease in Japan: Life study
Authors: Fukuda Haruhisa , Maeda Megumi , Murata Fumiko
Published: June 2023

Background

Alzheimer’s disease (AD) is a major public health problem. Although donepezil is used as a first‐line pharmaceutical treatment for AD, studies from various countries have reported low continuation rates. However, the only available data from Japan are from post‐marketing observational study reports. This study investigated the continuation rates of newly prescribed donepezil among AD patients in Japan.

Method

The study was conducted using health care claims data and long‐term care claims data from 17 Japanese municipalities participating in the Longevity Improvement & Fair Evidence (LIFE) Study. The study period was from April 2014 to October 2021, and the study population comprised patients who had been newly prescribed donepezil after receiving a diagnosis of AD. The treatment discontinuation was defined as a gap of ≥61 days between the last donepezil prescription and subsequent donepezil, cholinesterase inhibitors, or memantine prescription. Kaplan‐Meier curves were plotted to estimate the duration (days) from the start of a new prescription of donepezil until discontinuation, and patients were censored at the end of the observation period or death. The treatment continuation rates were also analyzed according to the patients’ certified long‐term care needs levels (ranging from levels 1‐5) at the time of the initial prescription.

Result

We analyzed 20,474 patients (mean age: 82.2 years, women: 65.7%) with a mean follow‐up duration of 483 days. The treatment continuation rates at 30 days, 90 days, 360 days, and 540 days after initial prescription were 89.1%, 79.4%, 64.5%, and 58.3%, respectively. By excluding patients with long‐term care needs levels 3‐5, we analyzed 18,924 patients with lower care needs levels (mean age: 82.0 years, women: 65.4%); their treatment continuation rates were almost identical to those of all patients (<1% difference). Within 60 days of donepezil discontinuation, only 2.9% and 3.1% of patients had been switched to galantamine and rivastigmine, respectively.

Conclusion

The AD patients showed a rapid discontinuation of donepezil and subsequent AD treatments by 90 days, and approximately 40% had ceased this therapy after 1.5 years. In view of the limited pharmaceutical options available for AD in Japan, this finding emphasizes the need for AD preventive measures in the pre‐clinical stage.