bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher allostatic load is associated with poorer structural integrity in the limbic network in cognitively unimpaired elderly
Authors: Palix Cassandre , Chocat Anne , Ferment Victor , Coulbaut Laurent , Felisatti Francesca , Haudry Sacha , Gonneaud Julie , Collette Fabienne , Mézenge Florence , Landeau Brigitte , la Sayette Vincent De , Vivien Denis , Chetelat Gael , Poisnel Géraldine
Published: June 2023

Background

Allostatic load (AL) is a cumulative measure of dysregulations across multiple physiological systems of the body occurring over time. AL was originally developed to explain how chronic stress damages physiologic systems and accelerates aging. Studies exploring the relationship between AL and brain health in older adults using a multimodal approach are limited. Our objective was to provide a comprehensive overview of the brain substrates of AL in cognitively unimpaired elderly using complementary multimodal neuroimaging techniques.

Method

Baseline data of 111 cognitively unimpaired older adults (mean age, 68.9years) from the Age‐Well study (NCT02977819) were included. They underwent multimodal neuroimaging (T1‐weighted and diffusion MRI, FDG‐PET and amyloid‐PET). A global measure of brain integrity was obtained for each modality by extracting the averaged signal across the whole gray matter (GM) or white matter (WM) for diffusion. AL was computed based on 19 markers of health. First, we examined the relationships between AL and sex or age. Second, we performed multiple regression and voxel‐wise analyses to predict AL from each neuroimaging modality and to highlight the brain regions involved. Finally, we conducted forward stepwise multiple regressions including the 19 AL‐components to determine the prognostic components of each of these associations; correcting for age, sex and education.

Result

AL was associated with sex (men>women) but not with age. Higher AL was associated with lower global GM volume and WM mean diffusivity. Adjusting for alcohol consumption, smoking habits, treatments or comorbidities, these associations remained unchanged. Association with lower GM volume was found in the parahippocampus, hypothalamus, anterior insula and prefrontal gyrus and with WM diffusivity in the corona radiata and corpus callosum. Stepwise regressions revealed that these associations with GM volume and WM diffusivity were mainly explained by the body mass index (BMI) and waist‐hip‐ratio (WHR), respectively.

Conclusion

Higher AL is associated with poorer structural integrity in regions of the limbic network, which is implicated in memory, emotion and stress processes and known to be particularly vulnerable to Alzheimer’s disease. Our results further suggest that maintenance of a healthy weight (by monitoring BMI and WHR) might help to prevent AL increase, thus promoting brain health.
Circadian disturbances, risk for postoperative delirium and conversion to dementia
Authors: Gao Lei , Li Peng , Gao Chenglu , Zheng Xi , Ulsa Ma Cherrysse , Wong Patricia M , Rutter Martin K , Scheer Frank AJL , Johnson‐Akeju Oluwaseun , Hu Kun
Published: June 2023

Background

Delirium is one of the most common complications in older adults after surgery. Circadian rest‐activity rhythms are known to be disrupted with age, and among individuals with mild cognitive impairment and Alzheimer’s disease (AD), major risk factors for postoperative delirium (POD). However, the relationship between prior circadian rest‐activity rhythm measures and POD, and whether these measures can predict conversion from delirium to dementia has not been systematically assessed.

Method

64,852 UK biobank participants between 2013‐2015 (mean 57.9y [SD = 8.0], 54.0% female) were assessed with actigraphy for 7 days, followed by at least one surgical event requiring hospitalization during follow‐up until 2021. Four measures were extracted from actigraphy to quantify circadian rest‐activity rhythms, which were amplitude (representing the strength), acrophase (representing peak activity time), interdaily stability (IS), and intradaily variability (IV; representing the fragmentation) of 24‐h rhythm. Earliest occurrence of delirium and dementia were determined using ICD‐10 coding from hospitalization records, and POD was defined as delirium within 3 days of an operation. Cox proportional hazards models were used to assess whether circadian disturbances in these rhythms predicted increased risk for delirium including POD, and logistic regression for the risk of conversion from delirium to dementia within 5 years of the first delirium occurrence.

Result

Risk for new POD during hospitalization (n = 249) was increased with lower amplitude (1 SD decrease, hazard ratio [HR] 1.28, 95% CI: 1.10‐1.49, p = 0.002), and higher intradaily variability (1 SD increase, 1.30, 1.12–1.51, p<0.001) after controlling for demographics, lifestyle factors, cardiovascular risk, and morbidity burden. These results were consistent when all new delirium cases during hospitalization (n = 500) were included. Within 5 years, 47 developed incident dementia. Every 1‐SD decrease in amplitude within a cohort of was associated with increased odds of incident dementia (odds ratio 1.44, 1.06‐1.96, p = 0.02) independent of age at first delirium and sex.

Conclusion

These results indicate a link between circadian disturbances and risk for delirium, as well as conversion to incident dementia. This is novel evidence that circadian disturbances are part of the shared common underlying pathophysiological mechanisms between delirium and dementia that warrant further investigation.
Underrepresented minorities in US dementia clinical trials 2010‐2020: A systematic review
Authors: Neugroschl Judith A. , Sewell Margaret , Zhu Carolyn W , Dauray Adeleine , Melnick Jonah , Pomerantz Erin , Ryan Catherine , Walsh Samantha , Loizos Maria , Evans Kirsten , Meuser Caroline , Pun Kelly , Martin Jane , Sano Mary
Published: June 2023

Background

Though Alzheimer’s disease and related dementia (ADRD) risk is higher among Blacks (13.8%) and Hispanics (12.2%) compared to non‐Hispanic whites (10.3%), diverse groups are underrepresented in randomized control trials for dementia. This systematic review examined reports of race/ethnicity in RCTsfrom 2010‐2020 and included pharmacological, nutraceutical, nutritional, TMS or other CNS interventions for AD.

Method

A comprehensive search was executed in MEDLINE/Embase of published RCTs on MCI/AD participants from 2010‐2020. Using Covidence software, study selection was conducted independently by 10 trained reviewers. Two reviewers independently screened each article for inclusion, abstracted data. Conflicts were resolved by senior authors. 3,281 articles were reviewed, 515 assessed for eligibility, with data extraction conducted on 148; data presented focused on 85 studies conducted in the U.S. Average number and proportion of participants in studies that reported each race/ethnic group were computed.

Result

49/85 (58%) studies reported race/ethnicity in some way: 15 reported race and ethnicity as separate variables, 10 reported race/ethnicity as one variable (i.e., non‐Hispanic Black), 15 did not specify if race and ethnicity were separate variables, and 11 only reported the % of Whites. Of the 49 studies that reported any race/ethnicity information, all 49 reported the number of White participants, who on average constituted 85.4% (range 30‐100%) of study samples. In the 35 studies that mentioned Blacks, Blacks constituted an average of 8.6% (range 0‐33%) of study samples. In the 16 studies that mentioned Asians, the mean was 6.7% (range 0‐47%). Only 3 studies mentioned Native Americans, representing 1% (range .8‐1.4%) of study samples. 28 studies reported Latinx’s: they accounted for a mean of 13.4% of the samples (range 0‐92%).

Conclusion

Despite efforts to improve diverse recruitment, just over half of studies conducted in the U.S. reported race/ethnicity at all, and those that did frequently presented data in a manner that is difficult to interpret (e.g., only % of Whites). Underrepresented minorities continue to be grossly underrepresented and/or underreported in dementia clinical trials.
Early detection of Alzheimer’s Disease using MRI images and deep learning techniques
Authors: Nagarathna C R , Kusuma M M
Published: June 2023

Background

Alzheimer’s is a neurodegenerative disease that diminishes the capability of individuals to perform their daily activities. It is an irreversible disease once it is started not able to stop it but early detection of the disease can help to slow down the progression of it by starting early treatment. In this experiment, we use MRI images and clinical study data available at the Alzheimer’s Disease Neuroimaging Initiative data set to detect the different stages of Alzheimer’s and forecast the duration required for the conversion from mild cognitive impairment to Alzheimer’s. The clinical signs of Alzheimer’s disease are portrayed by Age, patient education details, the progression rate of disease, and cognitive information. Done experiment by using Machine learning and Deep learning techniques like multi perceptron networks, Random forest, SVM, and decision tree classifiers to do binary and multi‐classification of Alzheimer’s Disease(AD), Late Mild cognitive impairment (MCI), Early cognitive impairment (EMCI), and Cognitive control(CN).

Method

Deep learning technique

Result

an average the model achieved 91.25% of precision indicates 91.25% total positive images are correctly classified, 91.25% of sensitivity indicates 91.25% of total images are detected remaining are not, and achieved 95.52% of accuracy

Conclusion

Alzheimer’s is a neuron degenerative disease. Currently no treatment is available to cure AD or to stop progress of disease. But detection of dementia at its early stage might help individual family to think about their future regarding financial issues. In this work we tried our best to categorize the different phases of AD. We used a deep neural network and achieved an accuracy of 95.52%.
ApoE4 binding in dried blood spots is associated with lower cognition in a population‐based sample of 50+ non‐demented adults
Authors: Araujo Yacila I. Deza , Weiss Luzia M , Groh Rebecca , Horton Hannah M. , Borbye‐Lorenzen Nis , Skogstrand Kristin , Holmgaard Solveig , Andersen‐Ranberg Karen , Ludmark Vania Panes , Börsch‐Supan Axel , Börsch‐Supan Martina , Rieckmann Anna
Published: June 2023

Background

The ApoE ε4 allele is a major risk factor for late‐onset Alzheimer’s disease and cognitive decline in ageing (Corder et al., 1993) but the role of the circulating ApoE4 protein on cognition is still under debate (Simon et al., 2012; Wang et al., 2014). Here, we report the distribution of circulating ApoE4 protein, assessed from dried blood spots, in a large population‐based sample. Preliminary analyses examined its associations with cognition and lifestyle factors.

Method

Measures of memory (word recall), verbal fluency and dried blood spot samples were collected during the 6th Wave of the Survey of Health, Ageing and Retirement in Europe ‐ SHARE (N = 12,531, 50y and over, 59.3% females). An assay to specifically bind to the ApoE4 protein in dried blood spots was developed. Data driven cut‐offs were tested to divide the ApoE4 binding distributions in specific and non‐specific types. Next, multiple linear regressions were used to test the association between ApoE4 binding type and cognition. Models were adjusted for available demographic, lifestyle and health‐related variables. Interaction terms between age and ApoE4 binding type were created. Finally, specific binding levels were used as a continuous outcome to assess whether they were associated with demographic, health or lifestyle variables.

Result

A cut‐off of 50.000 pg/mL was chosen to separate the distributions of specific (28.4%) vs. non‐specific (71.6%) ApoE4 binding (Fig. 1). Belonging to the specific binding group had a significant negative effect on word recall (ps < 0.001) but not on verbal fluency. Interaction effects between age and specific ApoE4 binding were observed in all models, with the effect of specific ApoE4 binding on cognition magnified for adults aged 75‐84y (Fig. 2A, 2B and 2C). Finally, higher BMI, female sex and hypertension (all ps < 0.05) were predictors of higher levels of specific ApoE4 binding.

Conclusion

Specific and non‐specific binding to the ApoE4 protein, assessed in dried blood spots, followed known population frequencies of ApoE ε4 allele (Gerdes, 2003). Specific ApoE4 binding was associated with worse cognitive performance. Higher specific ApoE4 levels were associated with female sex and cardiovascular factors.
Accelerated long‐term forgetting‐ALF in Mild Cognitive Impairment: A sensitive tool for subtil memory problems
Authors: Berrios Waleska , Campora Nuria , Fernandez Maria Cecilia , Genero Agustina , Rugiero Marcelo , Golimstok Angel
Published: June 2023

Background

Accelerated long‐term forgetting (ALF) has been considered a memory consolidation problem, whereby a person can learn and recall information accurately for a limited period of time, but then exhibits a long delayed recall deficit. Standard episodic memory tests which assess long delayed recall consider a delay interval up to 40 minutes after the initial learning. ALF could not be detected by this method. The aim of this study was examining ALF phenomenon in a population of Mild Cognitive Impairment (MCI) patients and normal cognitive performance (NC) individuals.

Method

Patients with cognitive complaints were included during a period of 1 year, according to selection criteria. A standard neuropsychological test battery was administered. In order to assess ALF we used the Logical Memory (LM) subtest of Signoret’s memory battery. We registered immediate recall, delayed recall at 30‐minutes and long delayed recall at 7‐days. We also proposed that the performance of long delayed recall at 7‐days ≤50% of the value of delayed recall at 30‐minutes in LM could be considered ALF.

Result

During a 1 year‐period 115 patients were included, as “G1” 84 MCI patients and “G2” 31 NC individuals. Demographics data: 1) G1 mean age was 73.06±9.99 years, mean education was 12.17±4.28 years and 39(46.42%) were females; 2) G2 mean age was 67.03±8.28 years, mean education was 14.4±3.8 years and 24(77.41%) were females. The performance in memory tests showed that G1 had lower values in long delayed recall at 7‐days compared to G2 with statistical significance (G1 3.65±2.59 vs G2 6.16±2.6; p = 0.001). When we applied our proposal for ALF, just 7(22.6%) patients of G1 and 26(31%) of G2 had a performance of long delayed recall at 7‐days ≤50% of the value of delayed recall at 30‐minutes in LM without statistical difference (p = 0.378).

Conclusion

Until the date, there isn’t an agreement in memory test to use or delay interval to consider or normative data available to detect ALF. While our proposal doesn’t differentiate between MCI and NC patients, it is necessary to continue studies and produce normative data.
Assessing biomarkers of awareness in people with advanced Alzheimer’s disease in care homes‐ a feasibility and pilot study
Authors: Huntley Jonathan D
Published: June 2023

Background

There is an urgent need to understand the nature of awareness in advanced AD to ensure effective person‐centred care. As dementia progresses, it can become very difficult for family members and caregivers to understand the lived experience of a person with advanced dementia, and assumptions are often made about their level of awareness and quality of life based on observations of behaviour. However, such observations are subject to bias and misinterpretation. In addition, there are anecdotal reports of variability of awareness with apparent moments of lucidity, however there is no objective data on how this relates to changes in underlying brain activity or subjective experience.

Method

This feasibility and pilot study uses of electrophysiological and physiological biomarkers to assess awareness and emotional responsiveness in a real‐world setting. These approaches include 1) 7 channel EEG 2) Bispectral index monitoring 3) physiological markers of emotional response (heart rate, electrodermal activity, accelerometry, temperature). These data were collected during a 1 hour protocol involving rest, musical stimulation, visual stimulation and interaction with caregivers.

Result

We report the feasibility of using these approaches in 15 people with advanced dementia (sMMSE 0, CDR 3) who reside in specialist dementia care homes. Data was collected in the ‘real world’ care home setting and was feasible and acceptable to people with advanced dementia, family members and care home staff. Preliminary data will be presented on baseline biomarkers of awareness and arousal in advanced AD, and whether EEG and physiological markers can differentiate between rest and emotionally salient conditions.

Conclusion

These biomarkers provide experimental approaches to assess awareness and improve understanding and care for people with advanced AD.
Involvement of striatal motoric subregions in familial frontotemporal dementia with parkinsonism harboring the C9orf72 repeat expansions
Authors: Liu Li , Liu Shuying , Chu Min , Xie Kexin , Cui Yue , Rosa‐Neto Pedro , Wu Liyong
Published: June 2023

Background

The chromosome 9 open reading frame 72 (C9ORF72) has been proposed as the causative gene of frontotemporal dementia with parkinsonism (FTDP), but its pathophysiological mechanism of parkinsonism is poorly understood.

Method

To explore the roles of striatal motor subdivisions in the pathogenesis of parkinsonism resulting from C9ORF72 repeat expansions in the FTDP, two patients with FTDP from one pedigree and seventeen healthy controls were enrolled. The participants received clinical interviews and underwent neuropsychological assessments, genetic testing, [18F]‐fluorodeoxyglucose PET/MRI, and [18F]‐dihydrotetrabenazine PET/CT. Voxel‐wise and region of interest analysis were conducted with respect to gray matter volume, metabolism, and dopamine transport function between patients and controls, focusing on the motor part of the striatum according to the Oxford‐GSK‐Imanova Striatal Connectivity Atlas.

Result

Patient 1 presented with parkinsonism as the initial symptom, while patient 2 exhibited behavior disturbance as the first symptom, followed by parkinsonism within one year. Both patients had the hexanucleotide expansion detected in C9ORF72(>52 repeats). Gray matter volume atrophy, hypometabolism and dopamine dysfunction were observed in the motor areas of the striatum. Of the two patients, marked glucose hypometabolism within the striatal motor subregion was observed in patient 1, with corresponding gray matter atrophy. In addition, presynaptic dopaminergic integrity of patient 2 was deteriorated in the motor subregions which was consistent with gray matter atrophy.

Conclusion

These findings provide evidence that C9orf72 repeat expansions could result in degeneration and dopaminergic dysfunction of the striatal motor subregion, which contributed to parkinsonism in FTDP.
Circulating extracellular vesicles of neurovascular origin are elevated in women with severe preeclampsia years after their affected pregnancies
Authors: Suvakov Sonja , Norby Alexander , Abou‐Hassan Coline , Milic Natasa , Rajovic Nina , Jayachandran Muthuvel , Kantarci Kejal , Mielke Michelle M. , Garovic Vesna D
Published: June 2023

Background

Preeclampsia (PE), a pregnancy specific hypertensive disorder, has been associated with elevated risk for strokes, cognitive decline, and smaller brain volumes later in life. As severe PE has been associated with the highest risks for cerebrovascular disease, we hypothesized that circulating extracellular vesicles (EVs) of neurovascular origin will be detectable in women years after severe PE as a marker of persistent neurovascular damage and amyloid‐β.

Method

A cohort of 40 women with histories of normotensive pregnancies (control group) and age‐ and parity‐matched to 40 women with history of mild (n = 33) and severe (n = 7) PE were identified using the Rochester Epidemiology Project. Diagnosis of severe PE was ascertained based on clinical criteria (Table). While none of the women had any major cardiovascular events, our previous study of this cohort has demonstrated that total gray matter volumes were smaller in women with a history of preeclampsia and late‐life hypertension compared with the other groups. Blood‐borne EVs derived from neurovascular cellular activation were determined by standardized digital flow cytometry. Plasma concentration of amyloid‐β was measured by ELISA. Differences among the groups were tested by ANOVA, with the least difference test for pos hoc analysis. The association between EVs and MRI brain imaging was assessed by Pearson correlation coefficient.

Result

Women with history of severe PE had a significantly higher concentration of amyloid‐β carrying EVs compared to controls (p = 0.003). EVs positive for the markers of blood‐brain barrier‐ endothelial damage (LDL‐R) and inflammatory coagulation pathway activator (tissue factor), were significantly higher in women with history of severe PE compared to controls (p = 0.008 and p = 0.002, respectively), as well as to the women with history of mild PE. Plasma concentration of total amyloid‐β was also significantly greater in women with history of severe vs. mild PE (p = 0.037) (Table). The number of tissue factor positive EVs was negatively correlated with total gray matter volume (cm3) (p<0.05).

Conclusion

Women with a history of severe PE demonstrate elevated levels of markers of neuroinflammation and neurovascular damage, as well as greater amyloid‐β secretion. Excessive inflammation may contribute to previously described brain atrophy in these women.
Semantic variant Primary Progressive Aphasia: Additional semantic features in Chinese language users
Authors: Tee Boon Lead , Chen Lorinda Li‐Ying Kwan , Chen Ta‐Fu , Wang Pei‐Ning , Lu Chien Jung , Chan Andrew LT , Gorno‐Tempini Marilu
Published: June 2023

Background

To date, most literature on Primary Progressive Aphasia (PPA) has been based on English language users. Yet, there are more than 7,000 living languages worldwide with vast heterogeneities in their linguistic features. Contrary to English language, Chinese language is a classifier language in which it is grammatically mandatory to have classifiers present between numerals and nouns. In addition, Chinese characters typically have an abundance of homophones (i.e., words with same pronunciation but vary in orthography and meaning) and heteronyms (i.e., words with same orthography but vary in meaning and pronunciation). Chinese language users rely on semantic knowledge to identify the accurate classifiers, homophones, and heteronym pronunciations. Thus, we hypothesize that Chinese‐speaking semantic variant (sv) PPA patients have difficulties producing classifiers, homophones, and heteronyms.

Method

To assess classifier production, participants are presented with pictures of nouns. Participants are first tasked with producing noun‐specific classifiers spontaneously. If failed, they are presented with four classifiers to select. To evaluate homophone selection skills, participants are shown short sentences with one character/word removed. They are then tasked to complete the sentences by choosing one of the four homophones presented. For heteronym reading, participants are asked to read out loud Chinese compound words with heteronyms (e.g., “windmill” and “wind up”).

Result

We recruited 22 controls and 47 PPA individuals (12 svPPA, 10 nonfluent variant (nfv) PPA and 25 logopenic variant (lv) PPA). In classifier production test, svPPA and lvPPA patients produce fewer accurate classifiers (p<0.0001, p = 0.001), with svPPA showing least improvement when presented with multiple choices (p = 0.003). In homophone selection test, svPPA and lvPPA scored lower than controls (p<0.0001 and p = 0.007). For heteronym reading test, svPPA showed the lowest performance when tasked with reading heteronym characters (p = 0.001). Using voxel‐based morphometry, we noted that the ability to produce classifiers, read heteronyms and identify heteronyms are correlated with grey matter volumetric changes over the anterior portion of the left temporal lobe and fusiform gyri, brain regions associated with language semantic functions.

Conclusion

PPA symptomatology may vary across languages. Thus, studying PPA symptoms via a linguistically diverse approach potentially provides a more comprehensive understanding to the syndrome.
Cerebral amyloid‐β deposition in patients with diseases of the heart or carotid arteries: A systematic review and meta‐analysis
Authors: Starmans Naomi LP , Leeuwis Anna E , Biessels Geert Jan , Kappelle Jaap , van der Flier Wiesje M. , Tolboom Nelleke
Published: June 2023

Background

Cardiovascular disease is increasingly recognized as a contributor to cognitive impairment. Reduced cerebral blood flow alone does not explain this association. Another contributing mechanism could be increased cerebral amyloid‐β accumulation. We hypothesized that patients with diseases of the heart or carotid arteries have more cerebral amyloid‐β accumulation than patients without these diseases.

Method

We conducted a systematic review to determine whether there is an association between diseases of the heart (heart failure, myocardial infarction, heart valve diseases, arrhythmias and cardiomyopathies) or carotid arteries (stenosis or occlusion of the extracranial internal carotid arteries (ICA)) and cerebral amyloid‐β accumulation, measured with positron emission tomography. We searched Pubmed, EMBASE and Scopus for studies that matched inclusion and exclusion criteria. Where possible, we obtained standardized mean differences (SMD) of amyloid‐β standardized uptake volume ratios (SUVr) with a meta‐analysis using a random‐effects model.

Result

Seven cross‐sectional studies, two on heart diseases and five on carotid artery diseases, were identified, including a total of 1262 participants (mean age 60‐76 years, 53% female). Six of the seven studies did not find a difference in cerebral amyloid‐β accumulation between patients with or without heart or carotid artery disease. One study including 11 participants found more amyloid‐β in the hemisphere ipsilateral to an ICA stenosis than in the hemisphere of healthy controls. SMD were calculated for atrial fibrillation (AF) (two studies including 746 participants) and unilateral ICA stenosis or occlusion (two studies including 24 participants). Patients with AF tended to have more cerebral amyloid‐β than reference participants (SMD in SUVr 0.14, 95% CI ‐0.06 – 0.34). There was less amyloid‐β in the hemisphere ipsilateral to the ICA stenosis or occlusion compared to the contralateral hemisphere (SMD in SUVr ‐0.13, 95% CI ‐0.70 – 0.43). Although we did not find significant effects.

Conclusion

Currently available evidence does not support the notion that diseases of the heart or carotid arteries predispose for a higher burden of cerebral amyloid‐β.
Subtle cognitive impairment is associated with subtle instrumental activities of daily living defecits, but not severity of memory complaints in sucjective cognitive decline
Authors: Ryu Seon Young , Lee Sang Bong , Lee Taek Jun , Jung Yu Jin
Published: June 2023

Background

Subjective cognitive decline (SCD) can be considered as the preclinical manifestation of Alzheimer’s disease. The objective of this study was to examine whether there would be differences of the clinical correlates due to evidence of subtle cognitive imparment (SCI) in inividuals with SCD.

Method

One‐hundred‐and‐fifty‐five individuals with SCD (mean age: 68.18 ± 8.09 years) were included in this study. The participants underwent clinical assessments and completed detailed neuropsychological tests. The functional assessment was performed by the Korean Instrumental Activities of Daily Living (IADL) scale. Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ) consisting of 16 items that describe everyday memory failure.

Result

SCD individuals with SCI (n = 20) had lower Mini‐Mental State Examination scores and showed lower performances in the neuropsychological tests than the SCD only group (n = 135). In addition, the SCI group had worse IADL performance than the SCD only group. There were no differenes in depressive symptoms and PRMQ scores between two groups.

Conclusion

In SCD individuals, SCI was associated with subtle IADL deficits, but not with the severity of self‐reported memory complaints, compared to the SCD only group. These results suggest that functional assesments would be helpful for the clinical evaluation of individuals with SCD.
Characterization of altered neuroenergetic patterns in Alzheimer’s Disease using combined FDG‐PET and sodium MRI
Authors: Haeger Alexa , Fuchs Annalena , Romanzetti Sandro , Bottlaender Michel , Boumezbeur Fawzi , Lagarde Julien , Rabrait‐Lerman Cécile , Holtbernd Florian , Sarazin Marie , Winz Oliver , Heinzel Alexander , Mottaghy Felix M. , Schulz Jörg B. , Reetz Kathrin
Published: June 2023

Background

[18F]‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) positron emission tomography (PET) is applied to delineate cerebral glucose metabolic patterns in Alzheimer’s disease (AD). Sodium MR imaging (23Na‐MRI) can reveal alterations in tissue sodium concentration (TSC) in the brain, potentially reflecting mitochondrial dysfunction and impaired cellular energy state. This initial study aims at investigating disease‐specific topographical associations between glucose metabolism assessed via FDG‐PET and regional TSC from 23Na‐MRI, thus improving our understanding of neuroenergetics alteration in AD.

Method

20 patients with a biological biomarker‐based diagnosis of prodromal/mild AD (mean age 68±7.5; 8 females; CDR 0.75±0.57, MMSE 23.9±4.2) received an FDG‐PET, 23Na‐MRI and 1H‐MRI at 3T magnetic field (Siemens Prisma). A variable flip angle method was used to obtain TSC maps (Coste et al., 2019). To control for inter‐individual differences, FDG‐PET and TSC images were intensity‐normalized to the brainstem to create normalized glucose metabolism (nFDG) and normalized TSC maps (nTSC) (de Souza et al., 2011; Nugent et al., 2020), respectively. The Hammersmith and VolBrain Segmentation atlases were applied for region‐of‐interest analysis and to create correlation matrices between nFDG, nTSC and normalized local brain volume.

Result

Regional nTSC negatively correlated with nFDG in AD patients mainly in temporal lobe structures and superior frontal gyri, indicating that decreased glucose metabolism was associated with increased TSC and vice versa. As expected, regional volume was positively correlated with nFDG in regions of the temporal lobe. When performing partial correlation controlling for volume, negative correlation clusters between nTSC and nFDG remained significant for superior frontal gyri and the anterior temporal lobes (Figure 1).

Conclusion

For the first time, the association between local glucose consumption rates and sodium concentrations were investigated in AD using combined FDG‐PET and 23Na‐MRI at 3T. Consistently to our recent findings of increased TSC in AD patients (Haeger et al., 2021), the negative correlations between nTSC and nFDG values in temporal and frontal brain regions, are confirming the interplay between reduced energy metabolism and sodium increase in AD, the exact nature of which remains to be determined.

References: Coste […]. Magnetic Resonance Imaging 2019.

Haeger […]. Alzheimer’s & Dementia 2021.

Nugent […]. Scientific Reports 2020.

de Souza […]. Brain 2011.
Who is at risk of dementia? Trajectories of cognitive decline from mild cognitive impairment to dementia and the factors which mediate this decline
Authors: Robson Kaye Victoria , Slight Sarah , Mc Ardle Ríona
Published: June 2023

Background

Mild cognitive impairment (MCI) is generally referred to as the transitional zone between normal cognitive function and clinically probable dementia disease. Prevalence of MCI varies across international studies and ranges between 3% and 42% depending on the classification criteria used .(1) It is thought that 3‐15% of MCI patients will progress to dementia each year. (2) Individual differences have been reported in how quickly cognition deteriorates, with several factors contributing to this. A systematic review was conducted to understand the trajectories of progression from MCI to dementia due to Alzheimer’s or Lewy body disease, and the mediating factors which influence the rate of progression.

Method

This systematic review was conducted according to the Preferred reporting items for Systematic reviews (PRISMA) guidelines. Searches were conducted across four databases including Web of science, Medline, Embase and PsycInfo. Participants were diagnosed with MCI at baseline and progressed to dementia of either Alzheimer’s dementia (AD) or dementia with Lewy bodies (DLB). Studies included were longitudinal and published in English language between 2004‐2021. A data extraction form was prepared, and key data extracted from all eligible articles. This review was registered with PROSPERO (Reference: CRD42022289243)

Result

Sixteen studies were included. The sample size ranged from 56 to 7118 participants across the studies and participants had been followed between 2 to 12 years. Higher progression rates and quicker trajectories of decline were reported with DLB compared to AD. Characteristics found in the rapid declining groups, include participants with a positive APOE4 status, visual hallucinations, low baseline cognition score, lower education (< 6 years), REM sleep behaviour disorder (RBD), cognitive fluctuation, higher ‘Geriatric Depression Scale’ (GDS) score, and were mostly males. Having >1 DLB feature increased the trajectories of decline. Neuropsychiatric symptoms (NPS), in particular, apathy and irritability predict greater rates of conversion to dementia.

Conclusion

Incorporating NPS symptoms into a revised criteria for dementia is worth considering. Although these symptoms have previously been reported, presentation of different combination of symptoms and factors has yet to be explored in greater depth. Further studies are needed to retrieve an accurate result in deprivation decile and how this impacts MCI progression.
Mild behavioral impairment linked to phenoconversion to Alzheimer’s disease and cortical thinning in mild cognitive impairment
Authors: Jin Yoon Eun , Lee Jun‐Young , Kwak Seyul , Kim Heejung , Kim Yu Kyeong
Published: June 2023

Background

Mild Behavioral Impairment (MBI) is a neurobehavioral syndrome characterized by later life emergence of sustained neuropsychiatric symptoms, as an at‐risk state for dementia (Ismail Z, Alzheimers Dement, 2016). However, the associations between MBI and a risk of phenocoversion to dementia and its neuroanatomical correlates in MCI are still unclear.

Method

A total 1326 older adults with MCI was followed for a mean of 3.0 ± 2.0 years. MBI was approximated using a transformation algorithm for the neuropsychiatric inventory at baseline. Two‐step cluster analysis was used to explore classes of 5 MBI domains (decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, abnormal perception/thought content). A Cox regression analysis was applied to investigate the association between the clusters and phenoconversion to AD. A subset of participants (n = 225) underwent 3D T1‐weighted MRI scans and cortical thickness was compared among the clusters of MBI domains.

Result

The cluster analysis identified 3 groups of participants: (1) people without MBI (47.8%, asymptomatic); (2) people with only affective dysregulation (29.3%, affective dysregulation); (3) people with relatively high probability of affective dysregulation, followed by impulse dyscontrol and affective dysregulation (22.9%, multiple domains). Compared to the asymptomatic, multiple domains was associated with a higher risk of phenoconversion to AD (hazard ratio = 2.589 [1.981 – 3.385], p = < 0.001), but affective dysregulation did not predict phenoconversion (1.204 [0.896 – 1.620], p = 0.219) (Fig 1). MCI individuals with symptoms in multiple domains revealed thinning in the bilateral superior and inferior parietal, superior temporal, and prefrontal cortex, and the right precuneus compared to those with only affective dysregulation (Fig 2). We did not find differences in cortical thickness between phenocoverter and non‐phenoconverter, and interaction of clusters of MBI domains and phenoconversion.

Conclusion

The multiple co‐occuring MBI domains in individuals with MCI are associated with a higher risk of phenoconversion to AD. Moreover, MCI individuals with symptoms in multiple domains revealed cortical thinning in the superior parietal and precuneus, which have suggested as AD signatures (Dickerson BC, Cereb Cortex, 2009). These results suggest that evaluation of MBI and neuroimaging characteristics could be useful for risk stratification in MCI individuals.
Differential diagnosis of neurodegenerative diseases using an innovative deep learning approach
Authors: Redolfi Alberto , De Francesco Silvia , Crema Claudio , Archetti Damiano , Muscio Cristina , Firbank Michael J , Taylor John‐Paul , Tiraboschi Pietro
Published: June 2023

Background

Neurodegenerative diseases lead to memory disorders and cognitive impairments with major impacts on day‐to‐day function. Early detection of patients is essential for an efficient care approach, and differential diagnosis is essential for determining prognosis and tailoring management. Most research studies compare patients by pairwise comparison methods, but this does not correspond to daily clinical practice, in which clinicians need to distinguish many different possible types of dementia concomitantly. It has been shown that magnetic resonance imaging (MRI) can mark with good accuracy the different types of dementia, such as: Alzheimer’s disease (AD), Frontotemporal dementia (FTD), Parkinson’s disease (PD), dementia with Lewy bodies (DLB). Recently, Deep Learning approaches have started being used although differential diagnosis is still almost ignored. The aim of this study was to develop a Convolution Neural Network (CNN) to classify probable AD, FTD, DLB, PD and healthy elderly control (CN) subjects starting from Diffusion Tensor Imaging (DTI).

Method

The cohort used in this study came from six different initiatives: ADNI1, NIFD2, NACC3, PDBP4, PPMI5 and Newcastle University6,7,8,9. We analysed a total of 108 CN, 110 AD, 135 FTD, 150 DLB, 132 PD. Demographic and neuropsychological characterization is shown in Table 1. The DTI scans were pre‐processed using the FMRIB software library (FSL) with eddy current correction, skull‐stripping and diffusion tensor calculation. We post‐processed the Fractional Anisotropy (FA) map using 3D CNN. The proposed CNN structure consisted of an image input layer, convolutional filters, several batch normalization with max‐pooling layers and, finally, the classification layer. A data augmentation approach was adopted that ultimately resulted in a dataset of 26’450 brain scans. A hold‐out validation (70% training set 30% test set) was performed.

Result

We found excellent performance of the 3D CNN in discriminating the different neurodegenerative diseases. Figure 1 shows the confusion matrix with the following values for the area under the ROC curve in each class: 0.92 for CN, 0.90 for AD, 0.97 for DLB, 0.96 for FTD, 0.99 for PD.

Conclusion

These results prove that Deep Learning and the 3D CCN method are suitable for clinical practice and provide additional clues that can help clinicians in diagnosis making.
Dementia mediates the association of life‐course depression with mortality: A nationwide twin study
Authors: Yang Wenzhe , Wang Zhiyu , Li Xuerui , Qi Xiuying , Zhang Lulu , Pan Kuan‐Yu , Xu Weili
Published: June 2023

Background

Although the association between depression and mortality has been investigated, the impact of depression in different periods of life on mortality remains inconclusive. We aimed to examine the association of depression with all‐cause mortality from a life‐course perspective, and to explore the roles of dementia, as well as genetic and early‐life environmental factors shared by twins, in this association.

Method

From the Swedish Twin Registry, 44,919 twin individuals were followed for up to 18 years. Depression and dementia were ascertained using the Swedish National Patient Registry. Early‐life (<45 years), midlife (45‐64 years), and late‐life (≥ 65 years) depression were categorized according to the age of the first depression diagnosis. Deaths were identified through the Cause of Death Register. Generalized estimating equation model was used for unmatched analysis among all individuals. The mediating effect of dementia on the depression‐mortality association was estimated using generalized structural equation modeling. Conditional logistic regression model was used for co‐twin matched analysis among death‐discordant twin pairs.

Result

Among all the participants (mean age 59.34 years), 1,179 had a history of depression at baseline and 12,761 died during the follow‐up. In the unmatched analysis, the multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of all‐cause mortality were 1.71 (1.46–2.00) for depression at any age, 1.72 (1.36–2.17) for early‐life, 1.51 (1.19–1.90) for midlife, and 4.10 (2.02‐8.34) for late‐life depression. Mortality was significantly higher in individuals with late‐life depression than those with earlier‐life depression (P<0.05). Depression at any age was also associated with an increased risk of mortality with dementia (OR 1.62, 95% CI 1.28–2.05). In the mediation analysis, 56.74% of the depression‐mortality association was mediated by dementia. In the co‐twin matched analysis, the OR (95% CI) for the depression‐mortality association was 1.70 (1.22–2.38). No statistically significant difference in ORs between the unmatched and co‐twin matched analyses was observed (P = 0.09).

Conclusion

Depression, especially occurring in late life, is associated with an increased all‐cause mortality. Dementia in late life mediates over 50% of the depression‐mortality association, but genetic and early‐life environmental factors appear not to account for this association.
CSF neurodegeneration biomarkers predict MTL atrophy over time in cognitively healthy older adults
Authors: Vidal‐Piñeiro Didac , Capogna Elettra , Blennow Kaj , Halaas Nathalie , Idland Ane‐Victoria , Mowinckel Athanasia M , Pereira Joana B , Watne Leiv Otto , Zetterberg Henrik , Initiative Disease Neuroimaging , Walhovd Kristine B , Fjell Anders M
Published: June 2023

Background

Structural decline in the medial temporal lobe is an unspecific biomarker of neurodegeneration, assessed in normal older adults (OA) and Alzheimer’s Disease (AD). We investigated, in OA, whether CSF biomarkers of neurodegeneration (t‐tau, NFL, Ng, FABP3) predict longitudinal brain atrophy, whether this association is moderated by core AD biomarkers of beta‐amyloid (Aβ) and phosphorylated tau (p‐tau) and whether it is related to specific cellular and molecular mechanisms by using neurogenetic profiles.

Method

Longitudinal structural MRI up to 7 years and baseline CSF biomarkers levels were collected in 189 OA (mean age = 74.8 years). Hippocampus (HC) and entorhinal cortex (EC) were selected as regions of interest. Linear mixed and generalized additive mixed models (GAMM) were used to assess the effects of Biomarker, Time, and Time×Biomarker on EC thickness and HC volume. Similar models were used to assess the interaction with core AD biomarkers. Correlation between cortical decline maps, associated with CSF biomarkers, and gene‐expression maps (Allen Human Brain Atlas https://human.brain‐map.org/) for specific cellular components, was assessed with BrainSMASH package (https://brainsmash.readthedocs.io/en/latest/)

Result

Higher NFL, FABP3, and t‐tau CSF values were associated with steeper EC thinning and more HC atrophy (p<.05) over time (Figure 1a). GAMM showed significant non‐linear interactions with Time (except NG): NFL and FABP3 on EC (edf = 3.15, 3.81) and NFL and t‐tau on HC (edf = 3.09, 2.77) (Figure 1b). Aβ+ status (<550 pg/mL) did not significantly moderate the association with any biomarker (all tests p>.08) (Figure 2a). The relationships between CSF NFL with EC thinning (t = ‐3.27, p = 0.001) and HC atrophy (t = ‐2.91, p = 0.004), and FABP3 with EC thinning (t = ‐1.98, p = .05) remained significant, independently of p‐tau. The spatial pattern of cortical atrophy associated with the CSF biomarkers of neurodegeneration (Figure 2b) overlapped with distinct neurogenetic profiles: t‐tau with axonal growth cone (r = ‐.50, punc = .002); NFL with cortical cytoskeleton (r = ‐.61, pfdr<.001) and Ng with the dendritic shaft (r = ‐.40, punc<.009) components.

Conclusion

CSF NFL and FABP3 predict HC atrophy and EC thinning independently of Aβ/p‐tau. The neurodegenerative biomarkers may improve the accuracy of individual predictions of neurodegenerative changes in OA and identify those with a higher risk of future cognitive decline.
Diagnostic Value of Multi‐delay Multi‐parametric 3D pCASL in Early Alzheimer' Disease
Authors: Sun Mengfan , Wang Yanli , Li Runzhi , Jiang Jiwei , Zhang Yanlilng , Yao Zeshan , Li Wenyi , Zhang Yuan , Jia Ziyan , Xu Jun
Published: June 2023

Background

Single post‐labeling delay (PLD) pseudo‐continuous arterial spin‐labeling (pCASL) measures cerebral blood Flow (CBF). The altered CBF is associated with cognitive decline in early Alzheimer’s disease (AD). However, multi‐delay pCASL that measures multi‐parametric measurements including CBF, arterial cerebral blood volume (aCBV) and arterial transit time (ATT) has rarely been applied to AD studies and its diagnostic performance to recognize AD in early stage remains unclear. The purpose of this study is to compare the diagnostic value between the CBF measured by single PLD pCASL and the CBF/aCBV/ATT measured by multi‐PLD pCASL for early‐stage AD.

Method

Both 1 PLD and 7 PLD 3D pCASL protocols on 3T GE scanner were performed within one MR session for 26 cognitively normal (CN), 37 mild cognitive impairment (MCI) and 39 AD subjects who were recruited in Chinese Imaging, Biomarkers, and Lifestyle Study of Ageing Project (CIBL) from April to October 2021. Comparisons on CBF/aCBV/ATT in 10 regions of interest (ROIs), including left and right regions of olfactory, post cingulate, hippocampus, cuneus and precuneus, were performed across different groups. The area under the curve (AUC) were assessed through receiver operating characteristic (ROC) analysis.

Result

All ROIs showed significant decrease in CBF and increase in ATT of AD groups compared with that of CN and MCI groups (P < 0.05). There was no significant difference in aCBV between groups and CBF/ATT between CN and MCI (P > 0.05). The area under the ROC curve (AUC) of CBF in ROIs for both3D pCASL protocols was similar for discriminating AD against HC (0.949 vs. 0.965 for 1 PLD vs. 7 PLD, respectively), AD against MCI (0.836 vs. 0.830), MCI against HC (0.686 vs. 0.786). However, the combination of CBF/aCBV/ATT in ROIs measured by 7 PLD 3D pCASL could significantly improve diagnostic performance, which AUC was 1.000, 0.967 and 0.918 for identifying AD against HC, AD against MCI and MCI against HC respectively.

Conclusion

Multi‐parametric perfusion data from multi‐delay pCASL can improve the diagnostic value of AD in early stage, which could be a promising imaging biomarker in AD patients.