bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a home‐visit intervention on emotional well‐being for ethnic minority dementia family caregivers: Use of mindful breathing and compassionate listening
Authors: Lee Jung‐Ah , Gibbs Lisa
Published: February 2022

Background

Caregiving burden and depressive symptoms among ethnic minority family caregivers with limited English proficiency (LEP) caring for persons with dementia (PWDs) in the United States negatively affect their health status and quality of life. The purpose of this study was to provide a home‐visit intervention that was culturally appropriate and language specific delivered by community health workers (CHWs) using mindful breathing and compassionate listening to these caregivers to reduce their burden, depressive symptoms, and negative affect (NA) and improve positive affect (PA).

Methods

The study design used a pre and post intervention by bilingual CHWs visiting participants’ home weekly for a month. CHWs demonstrated compassionate listening of the caregivers’ concerns and issues about caring for PWDs. In addition, CHWs taught the caregivers to practice mindful breathing several times a day as needed that has been shown to reduce anxiety. Burden, depressive symptoms, PA and NA were measured at baseline and after the 4‐week intervention. Wilcoxon signed‐rank tests were used to examine the difference in each outcome.

Results

Twenty‐five ethnic caregivers recruited from local community centers participated (8 Latino, 8 Korean, and 9 Vietnamese; 11 spouses and 14 offspring caregivers). All participants completed the intervention. The English proficiency of participants was 1.3/5 (SD=.91); 20% (5 of 25) reported they cannot speak English at all. Ethnic group differences on outcomes were not significant allowing for pooling of the data. Burden was significantly reduced (Mpre = 49.44 ±16.07, Mpost = 41.88 ±17.46, p=.008) and depressive symptoms decreased but were not significant (p=.091). The PA was significantly improved (Mpre=3.09±1.0, Mpost=3.60±1.0, p=.025) but not the NA (p=.090).

Conclusions

These findings show the potential to reduce caregiving burden and improve positive affect in ethnic minority dementia family caregivers receiving home visits by bilingual CHWs. Caregivers had the opportunity to express their concerns and issues freely to CHWs who demonstrated compassionate listening and taught them mindful breathing. Larger scale studies should be conducted to examine long‐term outcomes to improve ethnic minority dementia caregivers’ emotional well‐being.
Theta‐gamma phase‐amplitude coupling explains the advantage of auditory plus visual gamma entrainment in Alzheimer’s therapy
Authors: Fatemi Seyyedeh Nahaleh , Sedghizadeh Mohammad Javad , Aghajan Hamid
Published: February 2022

Background

Impairment of gamma oscillations has been observed in cognitive disorders like Alzheimer’s disease (AD). Gamma entrainment using 40Hz auditory or visual stimulation has been proposed as a potential treatment for AD (Adaikkan et al., Trends in Neuroscience 2020; Sedghizadeh et al. Alzheimer’s and Dementia 2020), while simultaneous use of both modalities has been reported to show superior therapeutic results (Martorell et al., Cell 2019; Suk et al. Alzheimer’s and Dementia 2020). Gamma and theta oscillations are both produced in the hippocampal area and interact with each other. Evidence shows that the interaction between these bands leads to their phase‐amplitude coupling (PAC) in the frontal cortex (Amemiya et al., Cell Reports 2018). The current study assesses the effects of 40Hz auditory and visual stimulation on the theta‐gamma PAC, and suggests that the superior performance of multimodal entrainment can be explained by this marker.

Method

10 cognitively healthy participants were included in this study. Each participant was seated in a dark and quiet room and underwent three sessions of sensory stimulation (visual, auditory, and simultaneous (multimodal) visual and auditory) in a randomized order. Each session consisted of 60 trials of 5s stimulation and 5s rest. The auditory stimulation consisted of a 40Hz clicking sound modulated with a career frequency of 5kHz. The visual stimulation was generated using white LEDs flickering at 40Hz. EEG data were acquired and the theta‐gamma PAC was calculated using the time‐frequency mean vector length (tf‐MVL) method (Munia et al., Scientific Reports 2019).

Result

The PAC value for theta (4‐8Hz) and gamma oscillations near the stimulation frequency (39‐41Hz) on the Fz channel showed a significant increase during the multimodal stimulation intervals compared to the resting state, whereas the increase was not significant during the single‐modal stimulations compared to rest. The multimodal stimulation also involved more brain areas and resulted in a higher PAC compared to single‐modal stimulation.

Conclusion

Entraining gamma oscillations using simultaneous auditory and visual stimulation results in markedly superior theta‐gamma PAC compared to entrainment with single modalities. This superiority can explain the advantages reported for multimodal entrainment in AD therapy experiments.
Amyloid‐βeta peptides in CSF and plasma discriminate cerebral amyloid angiopathy from controls
Authors: Verbeek Marcel M. , de Kort Anna M. , Wermer Marieke J.H. , Marques Tainá M. , Kersten Iris , Schreuder Floris H.B.M. , Klijn Catharina J.M. , Stoops Erik , Brinkmalm Gunnar , Portelius Erik , Gkanatsiou Eleni , van Etten Ellis , Rasing Ingeborg
Published: February 2022

Background

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid‐beta (Abeta) peptides in the cerebral vasculature and has been associated with vascular dementia and intracerebral haemorrhages (ICH). Currently, the diagnosis of CAA is based on neuroimaging and includes the identification of lobar (micro‐)bleeds and cortical superficial siderosis. However, these MRI markers reflect only late‐stage manifestations and are therefore not suitable for an early diagnosis of CAA. We aimed to evaluate the diagnostic potential of the Abeta peptides AB1‐38, AB1‐40, AB1‐42, and AB1‐43 in cerebrospinal fluid (CSF) to discriminate (early) CAA from controls.

Method

We used immunoassays to quantify AB1‐38, AB1‐40 and AB1‐42 in CSF and plasma and AB1‐43 only in CSF. CSF from sporadic CAA patients (n=28) and controls (n=40), and plasma from hereditary Dutch CAA (D‐CAA) patients (asymptomatic and symptomatic), sporadic CAA patients (n=129) and controls (n=99) were analyzed.

Result

In CSF we found decreased levels of AB1‐38 (p=0.03; AUC 0.64), AB1‐40 (p=0.04; AUC 0.63), AB1‐42 (p<0.0001, AUC 0.87) and AB1‐43 (p<0.0001, AUC 0.92) in CAA patients compared to controls. In plasma we found significantly decreased levels of AB1‐38, AB1‐40 and AB1‐42 both in asymptomatic and symptomatic D‐CAA mutation carriers compared to controls. The concentrations of all Abeta peptides strongly correlated with each other (Spearman r>0.6, p<0.0001 for each comparison).

Conclusion

Abeta peptides have strong biomarker potential for the diagnosis of (early)_CAA. Interestingly, our results indicate that AB1‐43, which has shown to be relatively low‐abundant in vascular amyloid deposits, has the highest diagnostic accuracy to discriminate CAA from controls. In addition, we show that CSF AB1‐38 levels are decreased in CAA compared to controls.
Using natural language processing to identify signs and symptoms of dementia and cognitive impairment in primary care electronic medical records (EMR)
Authors: Maclagan Laura C , Abdalla Mohamed , Harris Daniel A , Chen Branson , Candido Elisa , Swartz Richard H , Iaboni Andrea , Stukel Therese A , Jaakkimainen Liisa , Bronskill Susan E
Published: February 2022

Background

Free‐text fields in electronic medical records (EMRs) are a rich source of information about persons with dementia. The signs and symptoms of dementia (e.g., responsive behaviours, cognitive impairment) can present to primary care providers many years before a formal diagnosis. We used natural language processing (NLP) to develop a list of features (i.e., dementia‐related key words) and compare classification algorithms to identify persons with dementia based on signs and symptoms documented in primary care EMRs.

Method

We used a validated algorithm based on administrative data to identify 526 persons with incident dementia (known positives) and 44,148 persons without (known negatives) aged 66+ from a primary care EMR database in Ontario, Canada between April 2010 and March 2018. A list of 900+ features associated with dementia was developed using literature review, clinician input and associated word embeddings. We trained a series of classification algorithms (e.g., gradient boosted models, neural networks, lasso and ridge regression) separately in progress notes and consult notes and compared their performance using nested 10‐fold cross validation.

Result

Persons with dementia were older (mean:80.3 vs. 74.6 years) and more likely to have 5+ chronic conditions (11.6% vs. 7.8%). Persons with dementia had a median of 30.3 features per progress note (IQR:23.8, 40.4) and 54.7 per consult note (IQR:26.6, 83.8) compared to 27.5 (IQR:21.3, 36.5) and 32.1 (IQR:14.0, 55.6) for persons without dementia. Out of eight thematic groups (cognition, social, health system use, function, medication‐dementia, medication, symptoms, other), persons with dementia showed substantially more features related to cognition, social and medication‐dementia in progress and consult notes compared to persons without dementia. Using progress notes, the classification algorithm involving neural networks showed the best performance (Sensitivity:66.2%, Positive Predictive Value [PPV]:81.3%). Using consult notes, the gradient‐boosted classifier performed best (Sensitivity:45.4%, PPV:66.5%).

Conclusion

We used NLP to discover informative features and develop classification algorithms to identify persons with dementia using free‐text EMR data. This could be used to improve recognition of early signs and symptoms of dementia by primary care providers to provide patients with appropriate interventions, including assessments, imaging and specialist referrals.
Domains and dimensions of family quality of life among families with a member with neurodegenerative diseases
Authors: Badia Marta , Orgaz‐Baz Begoña , Vicario‐Molina Isabel , Ortega Eva González , Aza Alba ,   NEUROQUALYFAM Group
Published: February 2022

Background

Family quality of life (FQoL) is a recent construct to be applied in neurodegenerative diseases (NDs). In this context, there is interest in advancing in the measurement of the FQOL as a first step to determine the supports that families need to perceive quality of life. The aim of this study was to test the validity of the Family Quality of Life Survey‐ Dementia (DiZazzo‐Miller & Samuel, 2011) in order to assess FQoL among family members of individuals with NDs who live in the cross‐border area of Spain‐Portugal.

Method

Three hundred family members of people with NDs completed the FQoLS‐NDs Survey (Badia et al., 2020). The mean age was 62.4 years (SD = 13.34). Most were males (70%), married (79.7%), not working (64.7%), with low income (66.1%), and had elementary/high studies (73.1%). The majority were the spouse/partner (40.9%) or son/daughter (51.7%) of the care‐recipient and played the role of primary caregiver (93.3%). Sixty percent of care‐recipients were females (M= 79.3 years; SD= 11.7). Sixty two percent presented dementia, 30.4 % Parkinson´s disease, and 7.6% multiple sclerosis. Construct validity was tested by correlation analysis to examine associations between domain level outcomes (i.e., health, financial well‐being, family relationships, support from others, support from services, influence of values, careers, leisure and recreation, and community integration) and global FQoL. Likewise, t‐tests were used to compare the outcome measures (attainment and satisfaction) within each of the nine family domains.

Result

Global attainment and satisfaction with FQOL‐NDs was found to be significantly correlated with composite attainment and satisfaction from nine domains (r=.489, p<.001 and r=.536, p<.001, respectively). Attainment and satisfaction were positively correlated within the nine domains (ranging from r=.83 to r=‐.69, p<.001). There was a significant difference between domain‐level attainment and satisfaction ratings [t(299)=12.28, p<.001, h2=.34]: the mean level of satisfaction experienced (M=3.71, SD=0.49) was significantly higher than that of attainment (M=3.52, SD=0.49).

Conclusion

This study demonstrates that FQOL‐NDs has good validity properties and it is a useful tool to establish FQOL profiles for family caregivers of people with NDs.
Life experiences of people with dementia in Vietnam and among the Vietnamese diaspora: A systematic review of qualitative studies
Authors: Nguyen Tuan Anh , Tran Kham , Hinton Ladson , Roughead Elizabeth E , Esterman Adrian , Dang Thu Ha , Kim Giang Bao , Pham Diep Bich , Nguyen Huong Thi Diem , Crotty Maria , Kurrle Susan , Pham Thang , Le Pham Tuan , Brodaty Henry
Published: February 2022

Background

As part of the effort to gather research evidence for the development of Vietnam’s National Dementia Plan, a systematic review was conducted to map dementia research in Vietnam or among the Vietnamese diaspora. This paper aimed to report the qualitative research evidence on the life experiences of people with dementia in Vietnam and among the Vietnamese diaspora.

Method

Systematic searches were conducted in June 2019 using Medline, Embase, Emcare, PsycINFO and Cochrane electronic databases, as well as grey literature. Keywords and Medical Subject Headings [MeSH terms] for dementia and associated terms were combined with keywords for Vietnam and its provinces. Qualitative research articles published in English or Vietnamese were included to examine evidence on the life experiences of Vietnamese people with dementia using thematic analysis.

Result

Our searches resulted in 3,940 papers, from which 21 qualitative research studies were included for final analysis. The majority of research has not been undertaken in Vietnam but with the Vietnamese diaspora in Western countries and has taken a cultural perspective to analyses. Research in Western countries has focused on the need for culturally adapted and culturally sensitive models of care. Emerging themes about the life experiences of Vietnamese people with dementia identified from the studies included: many people do not have diagnostic terms for dementia but use the descriptive language of symptoms; stigma was a reported problem and on occasions can be observed in the descriptive language used for people with dementia; cultural and traditional values create both an opportunity and a barrier, supporting compassion, family care and relaxation, but creating barriers to accessing health services or long‐term residential care.

Conclusion

This is the first systematic review reporting evidence on the life experiences of people with dementia in Vietnam and among the Vietnamese diaspora. Future research is needed on the voice of people with dementia themselves and their caregivers particularly in low and middle‐income countries with regards to living with dementia, pathways to care from diagnosis, treatment, care and support, additional social care and preparedness for end of life care for people with dementia.
Relationship of APOE, age, amyloid and clinical phenotype in Alzheimer disease
Authors: Whitwell Jennifer L. , Tosakulwong Nirubol , Weigand Stephen D. , Graff‐Radford Jonathan , Ertekin‐Taner Nilufer , Machulda Mary M. , Duffy Joseph R. , Senjem Matthew L. , Jack Clifford R. , Lowe Val J. , Josephs Keith A. ,   ADNI
Published: February 2022

Background

The apolipoprotein ε4 (APOE4) allele is the most common and well established risk factor for typical late‐onset amnestic Alzheimer’s dementia. Less is known about the role of APOE in patients with atypical clinical presentations of AD, with studies often disagreeing on APOE4 frequencies in these cohorts. We aimed to assess relationships between APOE genotype and age, amyloid‐beta (Aβ) deposition and clinical phenotype in Alzheimer’s disease.

Method

138 atypical AD patients (57 posterior cortical atrophy and 81 logopenic aphasia) were recruited by the Neurodegenerative Research Group at Mayo Clinic, and underwent APOE testing and Pittsburgh Compound B PET. 318 typical AD patients with APOE genotype and known onset age were identified from ADNI (121 had Aβ‐PET). Aβ‐PET was quantified using the centiloid scale. Logistic regression was used to estimate the proportion of APOE4 carriers by onset age and clinical group. Linear regression was used to estimate mean Aβ centiloid by age, APOE4 status, and clinical group in patients who were Aβ‐positive (centiloid≥19).

Result

The overall frequency of APOE4 carriers was lower in atypical AD (52%) compared to typical AD (66%), particularly for ε4ε4 homozygotes (9% vs 20%). APOE4 frequency increased with age in atypical AD, but showed a bell‐shaped curve in typical AD where highest frequencies were observed between 65‐70 years (Figure). Typical AD showed higher APOE4 frequencies than atypical AD only between the ages of 57 and 69 years. Aβ centiloid was higher in atypical AD compared to typical AD by approximately 16 centiloid units, but did not differ according to APOE4 status (Figure). Aβ centiloid stayed relatively flat with increasing age for both carriers and non‐carriers in atypical AD, but declines with increasing age in typical AD. Relationships between APOE4 and age, as well as centiloid, did not differ between the two atypical AD phenotypes.

Conclusion

APOE4 frequency differs between atypical and typical AD but is highly dependent upon age, with higher APOE4 frequency in typical AD only observed between 57 and 69 years. The findings highlight the importance of age and clinical phenotype in understanding the effects of APOE genotype in Alzheimer’s disease.
Factors influencing acceptance of technology across age: Amid the COVID‐19 pandemic
Authors: Whear Sarah A , Wilson Graham , Kourtesis Panagiotis A , Parra Mario A
Published: February 2022

Background

Digital technologies are creating unprecedented opportunities to improve and increase support to older people with cognitive and mental health problems, and to their family and carers. However, barriers that preclude the implementation of technology driven programs for the assessment and intervention of adults at risk of cognitive decline need to be better understood. This study investigated these outstanding issues, as well as considering the impact that the COVID‐19 Pandemic has had on such barriers.

Methods

A sample of 105 participants completed an online survey. Their ages ranged from 18 to 92 years. Of these, 72% were female, 83% had higher education and beyond, 42% were working, 42% were retired, and 14% were unemployed. The questionnaires assessed IT experience alongside awareness, attitudes, and stigmas regarding the use of technologies, particularly those used to support cognitive and mental health. Questionnaires also explored the impact of the COVID‐19 pandemic on these technology‐related factors. We compared these across groups of young (n=45), middle age (n=12) and older adults (n=48).

Results

Relative to younger participants, older participants were less aware of, and held stronger stigmas against healthcare technologies, even though they reported more IT experience. IT awareness was associated to more positive (r=0.619, p<0.001) and less negative IT Attitudes (r=‐0.271, p=0.015), more acceptability (r=‐0.374, p=0.001) and receptiveness towards technologies (r=‐0.610, p<0.001). Male participants appeared to be more aware of such technologies than female participants. However, relative to men, women had increased the number of ways and frequency with which they used technologies since the COVID‐19 pandemic started, and older people in general felt more inclined to endorse the need to learn more about healthcare technologies.

Conclusions

Having more accumulated IT experience throughout our lives may not necessarily lead to better acceptance of healthcare technologies. More awareness about such specific technologies will help overcome stigmas, and challenging environments such as those imposed by the COVID‐19 pandemic may lead to positive changes in perception and acceptance of such technologies. These are necessary steps towards the personalisation of healthcare technologies to support vulnerable adults at risk of dementia.
Brain microstructure mediates effects of tau on cognitive decline in early Alzheimer’s disease
Authors: Reas Emilie T. , Smirnov Denis S. , Banks Sarah J. , Galasko Doug R. , Brewer James B.
Published: February 2022

Background

Tau propagation from medial temporal regions to neocortex correlates with cognitive decline and neurodegeneration. Microstructural damage to medial temporal gray matter and associated white matter predicts Alzheimer’s disease (AD)‐related cognitive impairment. However, whether brain cytoarchitectural injury mediates effects of tau on cognitive dysfunction, or promotes cognitive decline via convergent pathways, remains unresolved.

Method

We used restriction spectrum imaging (RSI) to identify microstructural brain abnormalities associated with total tau, and to determine whether they mediate tau‐related cognitive decline. RSI, cerebrospinal fluid total tau, global cognitive function and verbal episodic memory data were acquired on 34 participants ranging from cognitively normal to mild AD (21 normal controls, 13 cognitively impaired (mild cognitive impairment or early AD)). Longitudinal RSI and cognitive data were collected two and four years post‐baseline, respectively. Restricted isotropic diffusion (RI), neurite density (ND), and isotropic free water (IF) were computed in hippocampus, entorhinal cortex, and six white matter tracts. Partial correlations examined associations among tau, microstructure, and cognition and mediation analyses assessed whether microstructure mediates tau‐related cognitive decline. Linear regressions compared the sensitivity of tau, amyloid and microstructure to cognitive outcomes. Partial correlations tested whether tau predicts subsequent microstructural change.

Result

Tau most strongly correlated with reduced RI, a measure of intracellular integrity, in the hippocampus and fornix. Tau and microstructure in all examined regions correlated with baseline and longitudinal cognitive performance. Hippocampal and fornix RI mediated effects of tau on cross‐sectional memory and global cognitive function, but direct effects of tau on cognition were not significant. White matter and entorhinal microstructure better predicted baseline memory and global cognition, and hippocampal IF better predicted global cognitive decline, than did tau or amyloid. Tau predicted more rapid decline in white matter RI and ND.

Conclusion

Markers of tau‐related neurodegeneration may reflect hippocampal and fornix injury that promotes memory impairment and dementia progression. However, medial temporal and white matter microstructure better predicts cognitive outcomes than tau and amyloid, implicating additional factors contributing to neural injury underlying cognitive decline. RSI may be useful for identifying microstructural brain abnormalities consequent to AD pathology or other risk factors, that signal early cognitive dysfunction.
Cardiovascular risk factors, white matter hyperintensities and executive function: Difference among Mexican Americans and non‐Hispanic whites
Authors: Vintimilla Raul , Hall James R. , Johnson Leigh Ann , Yaffe Kristine , Toga Arthur W. , O'Bryant Sid ,   The Health and Aging Brain Study (HABS‐HD) Study Team
Published: February 2022

Background

Cardiovascular risk factors (CVRF) differ between ethnicities but is not clear if the relationship with white matter hyperintensities (WMH) and executive function is also different. The purpose of this study was to examine the prevalence of cardiovascular risk factors and their effect on WMH and executive function in a sample of Non‐Hispanic Whites (NHW) and Mexican American (MA) elders.

Method

We studied 1100 (585 NHW, 515 MA) cognitively normal subjects from the Health and Aging Brain Study (HABS‐HD) with signed consent, 3T MRI (Siemens Skyra), clinical evaluation, and cognitive testing. WMH volume was measured from FLAIR using the Statistical Parametric Mapping (SPM) Lesion Segmentation Tool. Linear regression was used to predict the effect of CVRF on WMH. Log transformed WMH adjusted for intracranial volume (derived from Freesurferv6.0 analysis of T1 MPRAGE) were used to predict Trails B (executive function). Age, sex, and education were entered as covariates in the models.

Result

Sixty‐three percent of the sample were female. MA were significantly younger (mean age 62.6 vs 68.8), less educated (mean education years 9.84 vs 15.64), and had smaller WMH volumes (‐0.13 vs 0.02) than NHW. There was no difference on Trails B scores. MA had a higher prevalence of diabetes and obesity (p=<0.0001), but the prevalence of hypertension and dyslipidemia did not differ among the groups. WMH volume was associated with hypertension in both groups (p=<0.001), while the association with diabetes was only present on MA (p=<0.001). Dyslipidemia and obesity were not associated with WMH volume in any group. WMH predicted Trails B scores in NHW (B = ‐0.13, t =‐4.29, p = <0.001), and MA (B = ‐0.17, t = ‐3.25, p = 0.001). Results remained significant after adjusting for age, sex, education, and CVRF.

Conclusion

Our findings suggest that the association of CVRF with WMH differs among MA and NHW. Executive function was related to WMH volume in both groups, but it is likely that for MA a metabolic component is more important. Ethnicity should be considered when assessing the association of CVRF, small vessel disease, and cognition.
Amyloid‐β and tau pathologies relate to distinctive brain dysconnectomics in autosomal‐dominant Alzheimer’s disease
Authors: Guzman‐Velez Edmarie , Diez Ibai Palacio , Schoemaker Dorothee , Pardilla‐Delgado Enmanuelle , Fox‐Fuller Joshua T. , Vila‐Castelar Clara , Baena Ana Y. , Sperling Reisa A. , Johnson Keith A. , Lopera Francisco , Sepulcre Jorge , Quiroz Yakeel T.
Published: February 2022

Background

Alzheimer’s disease (AD)‐related pathology (i.e., amyloid‐β and neurofibrillary tangles) disrupts functional networks that support higher‐order cognitive functions. Yet, it is not well known how the brain’s functional architecture is differentially associated with in vivo pathology in preclinical AD, which is critical for predicting disease risk and progression. We intersected functional connectivity and PET images to examine how in vivo amyloid‐β and tau pathologies are associated with weighted‐degree centrality patterns, known to be important for understanding network organization and information transmission hubs, in cognitively‐unimpaired individuals with autosomal‐dominant AD due to the Presenilin‐1 (PSEN‐1) E280A mutation.

Method

21 cognitively‐unimpaired PSEN1 E280A carriers and 31 non‐carriers underwent resting‐state fMRI, 11C Pittsburgh compound B‐PET and 18F Flortaucipir‐PET. We used graph‐based network analyses to examine weighted‐degree centrality, the sum of weights from edges connecting to a node. A general linear model was used to compare connectivity maps between groups, and partial correlations were used to examine the relationship between individual‐subject maps with whole‐brain amyloid‐β and tau PET. A significance threshold of p<0.05 was used. Analyses were covaried for age and corrected for multiple comparisons.

Result

Compared to non‐carriers, mutation carriers exhibited reduced weighted‐degree in the medial occipitoparietal and posterior cingulate cortices. Greater amyloid‐β was associated with reduced weighted‐degree in the lateral temporal lobe and fusiform gyrus, and greater weighted‐degree in the lateral and medial prefrontal cortices. In turn, greater tau burden was associated with greater weighted‐degree in the lateral and medial temporal regions, anterior and posterior cingulate cortices, lateral parietal cortex and precuneus, and decreased weighted‐degree in dorsomedial prefrontal cortex.

Conclusion

Our findings show that cognitively‐unimpaired individuals who are genetically‐determined to develop AD dementia in their forties have abnormal patterns of functional connectivity that resemble spatial patterns of amyloid‐β and tau propagation. Regions that had weaker connections with nearby and distant regions showed greater amyloid‐β burden, while regions that were highly functionally connected exhibited greater tau burden, which has been suggested to increase the probability of tau seeding and propagation. These findings contribute to our understanding of how functional connectivity patterns can help predict risk and monitor AD progression from preclinical to clinical stages.
Anger in family caregivers of people with behavioral variant frontotemporal dementia versus Alzheimer’s disease
Authors: Chen Kuan‐Hua
Published: February 2022

Background

Ample evidence exists that family caregivers of a person with dementia (PWD) suffer a disproportionate level of burden, stress, and strain compared to non‐caregiving individuals. Less is known about the specific negative emotions experienced by dementia caregivers, such as anger. Anger is experienced by 40‐60% of dementia family caregivers and is associated with feelings of resentment towards the PWD. Anger may mediate aspects of caregiver well‐being and the quality of care of the PWD. Caregivers may experience increased anger due to behavioral symptoms of the PWD, but this has not been well‐characterized. Frontotemporal dementia (FTD), particularly the behavioral variant (bvFTD), is characterized primarily by behavioral symptoms. In contrast, cognitive symptoms may be more prominent in Alzheimer’s Disease (AD). We examined anger ratings of family caregivers for PWDs diagnosed with bvFTD, the two other FTD subtypes (i.e., semantic variant primary progressive aphasia [svPPA], and non‐fluent variant primary progressive aphasia [nfvPPA]), and AD.

Method

We studied 48 familial PWD‐caregiver dyads (19 bvFTD, 9 svPPA, 8 nfvPPA, 12 AD). PWD behavioral symptoms were assessed using the Neuropsychiatric Inventory (NPI). PWD cognitive symptoms were assessed using the Mini‐Mental State Examination (MMSE). Caregivers self‐reported their anger on the State Anger Scale.

Result

An ANOVA revealed that caregivers of people with bvFTD, svPPA, nfvPPA, and AD differed in anger (F=3.22; p=.03). Posthoc analyses revealed that bvFTD caregivers reported greater anger (M=1.50, SD=.46) than AD caregivers (M=1.18, SD=.21, p=.02). No other group difference was found. Follow‐up analyses revealed that within bvFTD and AD caregivers, higher caregiver anger was associated with higher scores on the NPI reflecting greater PWD behavioral symptoms (r =.63, p<.001), but not cognitive functioning on the MMSE (r=‐.03, p=.85). Importantly, PWD behavioral symptoms fully mediated the association between disease diagnosis (i.e., bvFTD vs. AD) and caregiver anger. We did not find a similar mediation effect for PWD cognitive functioning.

Conclusion

Anger among family caregivers is higher among those caring for persons with bvFTD compared to AD. Our findings reveal the important role that behavioral symptoms in PWDs play in explaining caregiver anger.
Neuronal networks are differentially affected in mutation carriers versus non‐carriers in autosomal dominant Alzheimer’s disease
Authors: Yang Kao Lee , Adluru Nagesh , McKay Nicole S. , Gordon Brian A. , Benzinger Tammie L.S. , Nair Veena A. , Prabhakaran Vivek , Alexander Andrew L. , Singh Vikas , Bendlin Barbara B. ,   Dominantly Inherited Alzheimer Network
Published: February 2022

Background

Autosomal dominant Alzheimer’s disease (AD) is caused by known genetic mutations which results in the biochemical consequences that underlie the pathological basis of the disease, and a disease process driven by amyloid accumulation. Mutation carriage is characterized by substantial amyloid accumulation, and dementia onset at or around the age of parental dementia onset. Dementia onset is likely due to neurodegeneration, including loss of neuronal networks, although changes to structural connectivity remain incompletely characterized. Here, we report preliminary connection‐wise analysis of neuronal networks based on mutation and cognitive status, as well as estimated years to symptom onset (EYO), in autosomal dominant AD.

Method

Cross‐sectional diffusion tensor imaging (DTI) data from participants in the Dominantly Inherited Alzheimer Network were analyzed. DTI pre‐processing was performed using FSL and MRtrix3. Network node regions were identified based on the IIT‐Desikan gray matter atlas. Threshold‐free network‐based statistics (TFNBS) method was applied to test the effect of group as well as the linear interaction effects of the EYO and group on neuronal networks. The groups examined were mutation carrying AD (AD:MC), cognitively unimpaired mutation carriers (CU:MC), and cognitively unimpaired non‐carriers (CU:NC). Age and sex were used as nuisance variables in the linear models.

Result

Sample characteristics are shown in Table 1. Group level effects are shown in Figure 1. EYO by group interaction effects are shown in Figure 2. The names of the corresponding gray matter regions are shown in Table 2. Threshold‐free network‐based ‐statistic matrices for the interaction effects are shown in Figure 3.

Conclusion

AD:MC and CU:MC groups had higher weighted totals (a proxy of intra‐axonal cross‐sectional area of fiber bundles) in most of the neuronal connections. In addition, a similar increase in the weighted totals was observed as CU:MC group approached EYO. Increased cross‐sectional area may reflect loosening and shortening of fiber bundles with disease progression. Characterizing these regions among cognitively unimpaired individuals may inform the specific disease pathophysiology that act upon brain structures and lead to dementia. Future studies will examine these patterns among individuals with late onset AD and assess longitudinal relationships.
Does a truly hippocampal sparing subtype of Alzheimer’s disease really exist?
Authors: Ferreira Daniel , Mohanty Rosaleena , Murray Melissa E , Nordberg Agneta K , Kantarci Kejal , Westman Eric
Published: February 2022

Background

The field of biological subtypes of Alzheimer’s disease (AD) has recently gained attention as a strong driver of precision medicine and future clinical trials. Neuropathology and neuroimaging studies have consistently identified four subtypes: hippocampal sparing AD, typical AD, limbic predominant AD, and minimal atrophy or minimal tau NFT AD. An important and still unresolved question is whether a truly hippocampal sparing subtype of AD can really exist, since it would challenge the widely accepted model of NFT spread. To address this question, we conducted a systematic review of the literature and performed original analyses on tau PET data.

Method

Our systematic review included a search on EMBASE, PubMed, and Web of Science databases up to October 2020. Original analyses included implementation of several methods for AD subtyping on tau PET, and utilization of five complementary cut points to identify hippocampal sparing AD cases both in published studies and in data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Result

In the three reviewed neuropathologic studies, we did not find any individual case with tau NFT in the association cortex while completely sparing the hippocampus (i.e., truly hippocampal sparing cases). In the in vivo tau PET studies, more lenient cut points consistently identified AD patients with tau NFT in the association cortex while completely sparing the hippocampus.

Conclusion

Our current data suggests that the hippocampal sparing subtype of AD does exist ante‐mortem, at earlier stages of the disease, but more research is needed to understand its pathogenesis and progression during life. Based on the findings from both in vivo tau PET and neuropathologic studies, we suggest that there are two possible independent pathways of tau spread: (1) a canonical pathway with early involvement of entorhinal cortex with subsequent involvement of limbic regions before eventually affecting multimodal association cortices, and (2) a less common pathway that affects multimodal association cortices with limbic involvement observed at end stages of the disease. As emphasized in the Murray 2011 study, hippocampal sparing relative to greater cortical involvement defines the phenotype.
Shared subcortical morphometry markers of cognitive impairment between Alzheimer’s and Parkinson’s diseases
Authors: Zhao Yuji , Goldman Jennifer , Merkitch Douglas , Gutman Boris A.
Published: February 2022

Background

Alzheimer's (AD) and Parkinson's (PD) diseases remain the two most widespread neurodegenerative disorders of our time. Though PD is far less prevalent than AD, its complex symptomatology can be useful in helping understand early progression of AD. Beyond cardinal motor symptoms, the majority of PD patients develop mild cognitive impairment (MCI), which is a common prodromal stage of AD. We employed spatially adaptive machine learning models to reveal shared morphometric signatures between AD and PD‐MCI

Method

We computed shape features in 7 subcortical regions based on T1‐weighted (T1w) MRI data from 239 PD subjects with normal cognition (PD‐NC) controls/120 de novo PD‐MCI patients from the PPMI cohort, and 225 controls (ADNI‐CTL) /398 ADNI‐MCI patients from the ADNI cohort. We first trained two separate sparse spatially regularized (TV‐L1) Logit models, one to distinguish ADNI‐MCI from ADNI‐CTL and the other to separate PD‐MCI and PD‐NC. We then coupled the training of the two Logit models, penalizing the model difference weighted by local mutual information (MI) of the linear weights’ patterns. We used ROC AUC scores to assess model accuracy. As the MI map itself is updated during training, it reveals the degree of similarity between the degenerative patterns. To test its statistical significance, we bootstrapped a distribution of MI weights when optimizing Logit models for randomly labelled ADNI and PPMI subjects. The nonparametric p‐values were corrected using searchlight False Discovery Rate.

Result

Out‐of‐sample ROC AUC for PD‐MCI prediction was 0.654 for the naïve model, and 0.704 for the joint model. Models and MI are displayed in Fig. 1. Only the left putamen showed a significantly similar pattern after FDR correction (Fig. 2).

Conclusion

We utilized a spatially adaptive machine learning model to discover shared imaging biomarkers of cognitive decline in AD and PD. Predictive accuracy improves when the two models are trained jointly. Such shared information may provide clues for pathological understanding of cognitive decline across common neurodegenerative diseases.
DeepADNet: A CNN‐LSTM model for the multi‐class classification of Alzheimer’s disease using multichannel EEG
Authors: Ho Thi Kieu Khanh , Jeon YoungHoon , Na Eunchan , Ullah Zahid , Kim Byeong C , Lee Kun Ho , Song Jong‐In , Gwak Jeonghwan
Published: February 2022

Background

Early and accurate diagnosis of Alzheimer’s disease (AD) – an incurable and progressive brain disorder, along with a sharp upward trend in the incidence rate, is significantly important for patients to take prevention and appropriate treatments. However, the pathophysiological mechanism at the levels of AD severity is still poorly understood in spite of the worldwide financial and research efforts. Using an inexpensive and noninvasive modality, such as Electroencephalography (EEG) coupled with Deep Learning (DL)‐derived diagnostic tool to retain the accuracy and versatility, therefore, has gained much attention in AD multi‐class classification.

Methods

The present study proposes DL model, named DeepADNet, for the AD multi‐class classification using multichannel EEG. First, we extracted the event‐related spectral perturbation (ERSP) features measuring the average dynamic changes in amplitude of three main EEG frequency bands relative to a specific experimental event. Second, the hybrid deep Convolutional Neural Network (CNN) ‐ Long Short‐Term Memory Network (LSTM) was built to exploit the wide range of ERSP patterns on a time‐frequency domain and to generate discriminant features to classify healthy controls (HC) with two AD subject groups. To tackle the imbalance problem and improve the classification accuracy, we also applied different over‐sampling techniques

Results

The EEG data were collected from the Oddball – a cognitive ability test with 63 subjects (23 HC, 17 Pre‐symptomatic AD (aAD) and 23 Prodromal AD (pAD) subjects) and the N‐back – a memory ability test with 36 subjects (13 HC, 11 aAD and 12 pAD subjects). We demonstrated that the ERSP patterns displayed significant differences among three subject groups during the two experimental stages. Classification results also reveal that a CNN‐LSTM model could overcome the existing methods utilizing the hand‐engineered features which demand on prior knowledge of AD analysis and achieved the highest accuracy during the Oddball (71.95% ± 0.019 and 75.95% ± 0.017) and during the N‐back (69.40% ± 0.003 and 73.70% ± 0.010) corresponding to original and SVMSMOTE‐based ERSP features.

Conclusions

These findings demonstrate the capability of the EEG systems to better underlie the AD progression through spatiotemporal‐dynamic regions in the brain and the potential of DL‐based models for further AD classification studies.
Evaluating frontoparietal network topography for diagnostic markers of Alzheimer’s disease
Authors: Rogers Bayard
Published: February 2022

Background

A group of mild, untreated AD patients (n = 63) and a control group of healthy age‐matched individuals (n = 73) were compared on amplitudes and latencies of the N4 and P6 ERP.

Method

Secondary EEG and behavioral data used for the present study was collected on participants while taking the Alzheimer’s Disease Evoked Potential Test (ADEPT) (Kilborn et al., 2009).

Result

We found a statistically‐significant difference in groups by N4 amplitude [F(1)=32.18, p < 0.001] and N4 latency [F(1)=31.41, p < 0.001], though linear models showed no interaction between these factors. A Tukey HSD post‐hoc test revealed significant pairwise differences between patients and controls (‐0.96 in N4 amplitude and 7.44 in N4 latency). We also found a statistically‐significant difference in groups by P6 amplitude [F(1)=11.12 p < 0.001] and P6 latency [F(1)=11.06, p < 0.001], and linear models showed no interaction between these factors. A Tukey HSD post‐hoc test revealed significant pairwise differences between patients and controls (‐1.13 in P6 amplitude and 7.70 in P6 latency).

Conclusion

Our results reveal a distinct N4/P6 ERP amplitude attenuation and subsequent component latency increase of mild untreated AD patients during cross‐modal memory tasks, while systematically showing statistically significant group effects in N4/P6 amplitudes and latencies of controls and patients making old/new recognition judgments. Our findings go further to provide evidence that N4 ERP anomalies are potentially more effective than those of their P6 counterpart for use as possible candidate AD biomarkers. Using EEG scalp topography, we visually demonstrate how and approximately where healthy control participants demonstrate neural cohesion through FPN shifting during cross‐modal tasks whereas the AD patients do not.
Grenzen der Verfahren zur Bewertung des Sommerlichen Wärmeschutzes nach DIN 4108‐2:2013
Authors: Freudenberg Peggy , Budny Oda
Published: February 2022

Die Methodik der DIN 4108‐2 zur Bewertung der Überhitzungswahrscheinlichkeit eines kritischen Raumes entspricht nicht mehr den wissenschaftlichen und technischen Standards. Die Kritik in der Fachliteratur hat zugenommen. Im vorliegenden Artikel werden die Hintergründe der DIN 4108‐2 erläutert und bekannte Anwendungsgrenzen und Unzulänglichkeiten aus der Literatur zusammengefasst. Diese betreffen sowohl angenommene Randbedingungen als auch die Abbildung der relevanten physikalischen Effekte und Bewertungsgrößen. Darüber hinaus wird dargelegt, dass Gebäudenutzung, Raumeigenschaften und Klima als relevante Kategorien in der Betrachtung des Überhitzungsrisikos differenzierter abgebildet werden müssen. Anhand von fünf Praxisbeispielen werden Widersprüche zwischen Ergebnissen des vereinfachten Sonneneintragskennwerte‐Verfahrens, Simulationen mit Randbedingungen gemäß DIN 4108‐2 und Simulationen mit gebäudespezifischen Randbedingungen aufgezeigt. Anhand eines Vergleiches von Mess‐ und Simulationsergebnissen für einen dieser Beispielräume werden auch Grenzen der Simulationsrechnungen angesprochen. Ziel der Darstellung ist es, zwischen der wissenschaftlichen Diskussion, die von stark idealisierten Fällen getragen ist, und den planerischen Herausforderungen der Praxis, in welcher die Anwendbarkeit dieser Nachweisansätze oft unklar ist, zu vermitteln.
A Research on Quality Evaluation of Eight Wild Edible Macrofungi Collected from East Mediterranean Region of Turkey
Authors: Kıvrık Merve , Süfer Özge , Bozok Fuat
Published: February 2022

Eight edible macrofungal species (Suillus collinitus, Rhizopogon roseolus, Lactarius sanguifluus, Lycoperdon molle, Ganoderma adspersum, Pleurotus cornucopiae, Lycoperdon perlatum, Macrolepiota procera) grown in Osmaniye were studied. Besides the evaluation of fresh forms, the mushrooms were dried at 40 °C, and the color, texture, protein and mineral contents, and bioactivities (total phenolic content, (TPC) and antioxidant activities by DPPH, FRAP and ABTS techniques) were determined. The protein, macro and micro mineral contents of dried samples were in range of 11.31–55.31 %, 132.75–50844.80 and 0.30–812.05 mg/kg, respectively. TPC of fresh samples were 10227.13–42216.89 mg gallic acid equivalent (GAE)/kg dry matter (DM) in methanolic solution, 3625.31–28809.99 mg GAE/kg DM in ethanolic solution, and decreased by drying process. ABTS method yielded higher results in fresh specimens, however, DPPH method in ethanol and FRAP method in methanol were the superior in dried forms.
Increases in prevalence rates for autism spectrum disorder: Clinical considerations
Authors: Walters Anne S.
Published: February 2022

Among those working with children across a variety of disciplines, an increase in children presenting with symptoms of autism spectrum disorder (ASD) has been questioned. Further, questions about whether this is truly an increase in incidence or related to improvements in diagnosis and identification have been widely discussed. At times professionals are reluctant to assign a diagnosis because we are trained to think that autism is a “rare” diagnosis. In fact, when I was first in practice many years ago, the rates were one in 10,000, and intellectual disability along with autism was common.