bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between bilateral oophorectomy and cognitive decline in older women from the Baltimore Longitudinal Study of Aging
Authors: Reuben Rebekah , An Yang , Resnick Susan M. , Einstein Gillian
Published: December 2021

Background

Nearly two‐thirds of individuals with Alzheimer’s disease (AD) are women, and the lifetime risk for AD is twice as high in women compared to men at age 45 (Alzheimer’s Association, 2019). Despite this increased prevalence, little is known about why more women develop AD. Early life events affecting 17β‐estradiol (E2) may be a potential mechanism behind this sex difference. E2 and/or ovarian loss leads to cognitive decline and neurodegeneration, which is mitigated with E2 (Gervais et al., 2020; Kantarci et al., 2018; Zeydan et al., 2019). Further, women with bilateral oophorectomy have an increased risk of AD in later life (Rocca et al., 2007). However, little is known about the long‐term trajectories of cognitive change post‐oophorectomy.

Method

The current study investigated cognitive decline over time in older women with bilateral oophorectomy (BO; n = 30; total visits = 131) prior to age 45 compared to spontaneously menopausal (SM; n = 61; total visits = 277) women from the Baltimore Longitudinal Study of Aging (BLSA; Shock et al., 1984). All participants were free of any dementia and completed a variety of demographic and cognitive assessments. Each eligible BO participant was age‐matched at a 1:2 ratio with a SM participant. Data were analyzed using linear mixed‐effects models in R 3.6.1 (R Core Team, 2019).

Result

Participants completed an average of four visits over 11‐years, and ranged in age from 52‐91 years. Our analyses revealed the BO group recalled significantly less words on the California Verbal Learning Test and made significantly more errors on the Benton Visual Retention Test over time than the SM group. Additionally, the BO group had poorer Digits Backward and Letter Fluency performance over time compared to the SM group.

Conclusion

Results demonstrate an association between BO prior to age 45 and greater longitudinal decline in executive function, verbal memory, visual memory, and working memory performance compared to age‐matched, spontaneously menopausal women. This is the first study to evaluate continuous cognitive decline post‐oophorectomy from midlife to older age, and suggests that even in normal aging, the early loss of E2 via BO may confer long‐lasting effects on cognition spanning decades of life.
The neural association between awareness of the self and of others: A brain imaging study of anosognosia and social cognition in early Alzheimer’s disease
Authors: Valera‐Bermejo Jose Manuel , Mitolo Micaela , Cerami Chiara , Dodich Alessandra , De Marco Matteo , Venneri Annalena
Published: December 2021

Background

A major proportion of patients with Alzheimer’s disease (AD) shows disorders of awareness in the early stages of disease that manifest as lack of/limited self‐awareness of their own cognitive deficits (anosognosia). Additionally, social awareness, i.e. aspects of social cognition, might also be impaired and reflect negatively on the patient’s capacity for self‐appraisal. The present study intends to explain the behavioural, brain structural and functional relationship between the presence of anosognosia and alterations in emotion and intention attribution in early‐AD, to understand the interaction between self/others awareness in the early stages of the disease.

Methods

Twenty‐nine early‐AD individuals underwent neuropsychological assessment to detect the presence of anosognosia and alterations in proxies of affective ToM. Additionally, T1‐weighted structural and resting‐state functional MRI scans were acquired and pre‐processed using the Statistical Parametric Mapping (SPM) 12 software. An independent component analysis (ICA) was performed at a group level to isolate and reconstruct four intrinsic connectivity large‐scale brain networks, namely fronto‐parietal, salience, and anterior and posterior default mode networks (DMN). Non‐parametric partial correlations were performed between the neuropsychological proxies of self‐other awareness. Functional and voxel‐based morphometry multiple regression outcome maps of anosognosia and ToM were visually overlapped and brain‐masks were devised to show statistical maps of the intersecting regions.

Results

A significant negative correlation was found between cognitive outcomes of anosognosia with emotion recognition (ρ= ‐.549, p=.004) and Theory of Mind (ρ=‐.671, p=.001). There were significant brain structure intersections between anosognosia and Theory of Mind in relation to grey matter reduction in the right anterior cingulate cortex (ACC) (BA24/32) and left caudate. Anosognosia/ToM functional maps showed only visual intersections of connectivity between the anterior DMN and the inferior occipital gyrus and precentral gyrus (FWE<0.05).

Conclusion

There seems to be an association between self and others awareness in early‐AD patients and its impairment appears to be underpinned by loss of neural tissue in the right ACC and subcortical regions. Similarly, the DMN seems to interact with specific occipito‐frontal regions, where visual information and mirror system dynamics might provide valuable resources to achieve self to other awareness in the presence of a neurodegenerative disease such AD.
Differential speech and language characteristics across neurodegenerative disorders
Authors: Robin Jessica , Xu Mengdan , DeSouza Danielle D , Gupta Anoopum S , Kaufman Liam D , Simpson Bill
Published: December 2021

Background

Speech and language changes have been reported to occur across a range of neurodegenerative disorders, including Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD) and Parkinson’s Disease (PD). Characterizing and quantifying such changes will enable the development of novel speech‐based measures to identify and monitor disease remotely and non‐invasively. In order to determine if such measures are disease‐specific, it is important to compare speech and language changes across different neurological conditions. In this study, we identify speech and language characteristics that are differentially affected across AD, FTD and PD populations.

Method

In this cross‐study comparison, we pooled data from normative studies of older adults (N = 299), and studies of individuals with a clinical diagnosis of AD (N = 895), FTD (N = 43) or PD (N = 42). In all studies, speech was recorded as participants performed a picture description task, in which they were shown a line drawing of a scene and asked to describe everything they saw in the picture. Speech samples were transcribed and analyzed, producing >500 acoustic and linguistic variables describing the characteristics of the speech sound and content. Speech variables were compared across groups using ANOVAs with a factor of diagnosis group, and significant group effects (p < 0.05) were further examined with pairwise group comparisons.

Result

Speech variables showing common or differential effects according to diagnosis were identified in this exploratory cross‐study comparison. Speech variables relating to the ease of speech production, including speech rate and number of pauses, were affected in all three diseases when compared to control participants. Select acoustic variables, including mean intensity and zero‐crossing rate, showed the greatest differences in PD compared to FTD or AD. Individuals with AD and FTD produced picture descriptions with less relevant information content. Select lexical variables, including pronoun and preposition use, were selectively affected in AD but not FTD or PD.

Conclusion

This study indicates that speech and language characteristics, derived from a picture description task, were differentially affected in AD, FTD, and PD. We found evidence for acoustic changes in PD, consistent with motor speech impairments, and linguistic changes in AD and FTD, consistent with cognitive impairments.
Automatic classification of AD versus FTLD pathology using speech analysis in a biologically confirmed cohort
Authors: Cho Sunghye , Shellikeri Sanjana , Ash Sharon , Liberman Mark Y. , Grossman Murray , Nevler Naomi , Nevler Naomi
Published: December 2021

Background

Logopenic variant primary progressive aphasia (lvPPA) is a non‐amnestic presentation of Alzheimer’s disease (AD). Many studies have proposed automatic classification systems comparing AD to healthy controls (HC), showing an accuracy range of 70%–88%, but have not included lvPPA, nor distinguished patients with AD neuropathologic change (ADNC) from patients with other neurodegenerative changes. We propose automatic classification systems that utilize language features to detect ADNC.

Method

Using automatic language processing tools, we extracted 34 language features from digitized 1‐minute picture descriptions produced by 69 patients with likely ADNC (49 amnestic AD (62.6±7.6y), 28 non‐amnestic lvPPA (63.2±7.1y); confirmed by autopsy or CSF analytes consistent with ADNC), 20 PPA patients with likely FTLD‐tau pathology (67.8±7y), and 35 HC (64.6±7y). Extracted features include part‐of‐speech categories per 100 words, lexical characteristics of content words (e.g. frequency, concreteness), and acoustic properties (e.g. pause rate, articulation rate). Multiple random forest (RF) and support vector machine (SVM) classifiers were built for three binary (ADNC vs. HC; ADNC vs. FTLD‐tau; lvPPA vs. FTLD‐tau) and one three‐way classifications (ADNC vs. FTLD‐tau vs. HC). We performed leave‐one‐out cross‐validation and feature selection with Pearson correlations (r <0.5 to 0.9) and t‐tests/ANOVA (p=0.01 or 0.05) in all models, and reported the best performance after hyperparameter tuning.

Result

The RF classifier of ADNC versus HC (features selected at r<0.7, p=0.01) had 90% accuracy (sensitivity=0.95, specificity=0.8, AUC=0.94) with prepositions, number of phonemes, and pause rate selected as the most important features. The SVM classifier of ADNC versus FTLD‐tau showed 93% accuracy (sensitivity=0.99, specificity=0.7, AUC=0.9), selecting features such as nouns, pronouns, and articulation rate (p=0.05). The RF classifier of lvPPA versus FTLD‐tau showed 85% accuracy (sensitivity=0.93, specificity=0.75, AUC=0.92), selecting features such as nouns, articulation rate, and total words (r<0.6, p<0.05). The RF multiclass classifier had 80% accuracy (sensitivity=0.92, macro‐average recall=0.7, macro‐average AUC=0.88) with word frequency, articulation rate, and number of prepositions selected as the most important features (r<0.6, p=0.01).

Conclusion

Automatic classifiers trained with language features extracted from one‐minute picture descriptions using our automatic pipelines showed high accuracy in identifying the pathological grouping of patients, which can potentially be used in the screening stage.
Tracking of the cognitive function and physical fitness in the older population from metropolitan area of Santos: Differences between the sexes
Authors: de Barros Vinícius Lucio , Bomfim Larissa Gomes Peres , Souza Melyssa Alves , Colovati Mileny Esbravatti Stephano , Zanesco Angelina
Published: December 2021

Background

Epidemiological studies have shown a difference between the sexes in the cognitive dysfunction in the elderly where women are more susceptible to Alzheimer’s disease than men. Evidence has reported that physical activity (PA) is an important strategy for brain health, but the exact mechanism by which PA would promote beneficial effects is not yet clear. The metropolitan area of Santos has the largest proportion of elderly population in Sao Paulo State (22%), but no studies shave examined the prevalence of Alzheimer’s disease in this population or whether there are differences between the sexes in the cognitive function. Therefore, this study aimed to evaluate the differences between the sexes in the cognitive function of the elderly from the metropolitan area of Santos.

Methods

This study was approved by the Ethical Committee Board from Medical School/UNIMES (Number: CAAE 20938619.4.0000.5509). One‐hundred and eleven women and fifty‐seven men were eligible for the study. Inclusion criteria were >65 years‐old, no severe cognitive impairment, preserved activities of daily living. Cognitive function and the level of PA were assessed by the mini‐mental state examination (MMSE) and Baecke questionnaire for older, respectively.

Results

The mean age of women was 75±3 and for men 73±1.4. There were no differences between the sexes in the MMSE score (27±1 and 27.3±1 for women and men, respectively), and approximately 23% of the participants were below the cut‐off reference values when the educational status was considered. Baecke score shows that the percentage of physically active women is lower as compared to men (44% and 54%, respectively, P<0.05).

Conclusion

There were no differences between the sexes in the cognitive function in the elderly even though women are less active than men.

Financial Support: Sao Paulo Research Foundation (FAPESP)
Detecting speech and language changes in early AD via automated analysis of clinical interviews
Authors: Robin Jessica , Xu Mengdan , Oday Abdi , Monteiro Cecilia , Liu Kai , Kahn Laura , Hejrati Mohsen , Amora Rainier , Simpson Bill , Teng Edmond
Published: December 2021

Background

Changes to speech and language patterns in Alzheimer’s disease (AD) may provide sensitive indicators of cognitive decline that could be automatically and objectively detected with speech analysis technology that incorporates natural language processing. In this study, we sought to determine whether analyses of audio recordings of open‐ended Clinical Dementia Rating (CDR) interviews collected as part of a Phase 2 clinical trial in prodromal‐to‐mild AD could identify speech and language characteristics relevant to clinical status.

Method

Speech recordings from baseline CDR interviews were analyzed for 101 English‐speaking AD participants (58F/43M; 30 prodromal/71 mild; mean age = 69 years, range: 53‐80) in the semorinemab (NCT03289143) Phase 2 Tauriel study. Recordings of the CDR interview were analyzed using the Winterlight speech analysis platform, which generates >500 variables describing acoustic and linguistic features of speech. We computed Pearson correlations between the speech variables and five clinical measures (CDR, ADAS‐Cog, RBANS, MMSE, ADCS‐ADL) to identify specific features related to clinical performance.

Result

CDR‐SB scores correlated more strongly with linguistic variables (e.g., types of words used, complexity of language) than acoustic variables. Participants with higher CDR‐SB scores (i.e., greater cognitive/functional impairment), used fewer past tense verbs when describing a recent event, a lower proportion of nouns compared to verbs, and shorter and simpler grammatical clauses (all r’s > 0.3, p’s < 0.05, FDR‐corrected). Similar associations were seen with other clinical assessments, and a subset of linguistic variables demonstrated significant (p < 0.05, uncorrected) correlations with all five clinical measures, including clause length, and use of prepositional phrases.

Conclusion

These analyses demonstrate that clinical interviews can be analyzed using objective automatic methods to generate speech variables relevant to clinical outcomes in AD. Individuals with greater cognitive and functional impairment used simpler language and fewer content words when describing a recent experience. Future work will include multivariate analyses of speech markers versus cross‐sectional clinical indices.
Characterizing dementia prevalence in the State of Florida: An electronic health record study
Authors: Miller Amber H , Marra David E , Wu Yonghui , Bian Jiang , Shenkman Elizabeth A , Maraganore Demetrius M , Smith Glenn E
Published: December 2021

Background

Alzheimer’s disease and related dementias (ADRD) are extremely prevalent and expected to significantly rise in the future. However, prevalence rates differ across ADRD sub‐types with Alzheimer’s disease (AD), vascular dementia (VaD), and dementia with Lewy Bodies (LBD) as the three most common. Aside from self‐report surveys, there is minimal research conducted in the state of Florida (USA) examining prevalence rates of ADRD across the lifespan.

Method

Electronic health record (EHR) data from the OneFlorida Research Consortium was used to examine prevalence rates of ADRD for individuals across the state. ICD codes were used to identify patients in Florida, aged 45+ years, living with ADRD. Descriptive statistics were calculated to characterize the OneFlorida ADRD population by decade of age, gender, ethnicity, and race.

Result

n = 162,356 individuals (5.66%) over the age of 45 with ADRD diagnosis in the EHR were identified. When age was not considered, the overall odds of having an ADRD diagnosis for males was lower than the odds of having ADRD diagnosis for females (Odds Ratio = .693, p < .0001). The unadjusted rate of ADRD diagnosis in the EHR for non‐Hispanic Whites (6.9%), while comparable, was significantly higher than the rates in Blacks (6.2%, χ2(1) = 226.13, p < .0001), Hispanics (6.1%, χ2(1) = 412.22, p < .0001), and other ethnoracial groups. The percentage of ADRD diagnosis increased with each decade of life. Of the ADRD sub‐types, AD was most common (62%), followed by VaD (23%), MCI (21%), LBD (5%), frontotemporal dementia (1%), and primary progressive aphasia (<1%).

Conclusion

ADRD diagnoses are common in patients throughout Florida. Although epidemiology studies suggest ethnic minorities are more likely to develop ADRD, non‐Hispanic Whites were more likely to be diagnosed with ADRD in this sample. This finding suggests a lack of access to diagnostic healthcare in ethnic minorities throughout the state, indicating a “double disparity”. This research will further examine how age, race, gender, and access to healthcare may moderate the rate of ADRD diagnosis. Understanding the trends and prevalence of ADRD may help inform policy makers, healthcare providers, and payers about disease management and may predict future healthcare needs.
Cancer survivors have a lower frequency of dementia in the 95+ oldest‐old
Authors: Lachner Christian , Camsari Gamze Balci , Ertekin‐Taner Nilufer , Thompson E. Aubrey , Petersen Ronald C. , Boeve Bradley F. , Lucas John A. , Reichard Ross R. , Dickson Dennis W , Knopman David S. , Graff‐Radford Neill R. , Murray Melissa E
Published: December 2021

Background

Advancing age is an important risk factor for dementia and cancer. An inverse association between these conditions has been described, yet caution from potential biases/confounders is warranted. Dementia and cancer may represent a spectrum of opposing dysregulated degenerative (apoptosis) and growth (proliferative) pathways respectively (Driver, 2014). Risk or resiliency factors affecting these pathways may influence cognitive outcomes in the oldest‐old. We sought to investigate demographics, clinical characteristics, and the impact of medical comorbidity on possible risk‐resiliency factors for neurodegeneration in nondemented and demented oldest‐old who died and underwent autopsy.

Method

Medical records of 161 decedents (female n=134) from the Mayo Clinic 95+ year‐old cohort (age range 95‐106 years‐old) were reviewed. Groups consisting of nondemented (n=72) and demented (n=89) decedents were stratified and compared according to demographics and clinical variables, including history of cancer. Autopsy and neuropathologic evaluation was also conducted.

Result

Age at death, sex, race, and education showed no differences between nondemented and demented decedents. History of cancer was higher in nondemented (57%) compared to demented decedents (30%) (p=0.002). APOE ε4 allele presence did not differ amongst groups, while APOE ε2 allele was more common in the nondemented group (p=0.026). History of coronary artery disease was higher in the nondemented (p=0.033). No differences were observed in other vascular risk factors, alcohol use, or depression. Smoking history approached significance and was higher in nondemented compared to demented (p=0.068). MMSE scores were higher in the nondemented group (p<0.001). Neuropathology findings included a lower Braak tangle staging in nondemented (median=III) compared to demented (median=V) groups (p<0.001) and less frequent diffuse plaques observed in the nondemented (67%) compared with those demented (93%) (p<0.001).

Conclusion

Dementia is less frequent among cancer survivors in the 95+ oldest‐old. Disease‐related mechanisms associated with malignancy and surviving it may be protective against neurodegeneration in the oldest old.
The relationship between homocysteine, oxidative stress, and cognition in mild cognitive impairment
Authors: Wang RuoDing , Bawa Kritleen , Feng Vivian , Herrmann Nathan , Gallagher Damien , Black Sandra E. , Ramirez Joel , Graham Simon J , Oh Paul I. , Andreazza Ana C. , Kiss Alex , Swardfager Walter , Lanctôt Krista L. ,   Neuropsychopharmacology
Published: December 2021

Background

Homocysteine (Hcy) generates reactive oxygen species and has been associated with cardiovascular disease and impaired cognition. While the relationship between Hcy and cognition has been extensively studied in other disorders, it has not been well characterized in mild vascular cognitive impairment (mVCI). Due to Hcy’s effect on vasculature and increased oxidative stress burden, individuals with elevated Hcy may be at greater risk of developing vascular dementia (VaD). This study investigated the relationship between Hcy, oxidative stress, and cognition.

Method

Participants were mVCI patients enrolled in a cardiac rehabilitation program. Cognition was assessed via National Institute of Neurological Disorders and Stroke and the Canadian Stroke Network (NINDS‐CSN) recommended battery, and blood was analyzed for Hcy and glutathione S‐transferase (GST), which modulates reactive oxygen species. Statistical analyses were performed using linear regression models in SPSS 26.

Result

There are 26 participants (73% male, 69% Caucasian, mean (SD) age=68.1 (7.2), years of education=15.7 (3.3)) with cardiovascular risk factors (62% hypertensive, 65% dyslipidemia, 31% diabetic, BMI=29.8 (5.1)) enrolled in the study to date. Mean plasma Hcy concentration was 13.4 μmol/L, with 9 participants classified as elevated (≥15 μmol/L). In preliminary analyses, plasma Hcy (stand. β=0.09, p=0.65) did not significantly predict executive function (F(2,23)=0.77, p=0.47) or verbal memory (F(2,23) =1.62, p=0.22). Hcy (stand. β = 0.684, p=0.013) significantly predicted GST activity (F(2,11) = 4.542, p=0.013, adj. R2 = 0.353), with a medium effect size.

Conclusion

Findings suggest that increased Hcy may be associated with compensatory increased GST activity in mVCI. A larger sample size will allow further analysis of cognition with additional covariates in this at‐risk population with increased oxidative stress.
Type and frequency of social contacts associated with low mood before and during the COVID‐19 pandemic in older adults: I‐CONECT project
Authors: Wu Chao‐Yi , Mattek Nora , Fleming Nicole , Scavone Colton , Wild Katherine , Kaye Jeffrey A , Dodge Hiroko H
Published: December 2021

Background

Social isolation is a risk factor for dementia, but the underlying mechanism is not well understood. It is possible that lack of social contacts negatively affects emotional well‐being, which leads to cognitive decline. To shed light on this potential mediation mechanism, we examined changes in type and frequency of social contacts and their effects on mood using data collected before and during the COVID‐19 pandemic among socially isolated older adults aged 75 and older.

Method

The data come from an ongoing randomized controlled trial, the Internet‐Based Conversational Engagement Clinical Trial (I‐CONECT, ClinicalTirals.gov: NCT02871921). One hundred forty‐six participants (age=81.0±4.5, 71.9% women) who were in the trial both before and during the pandemic and whose data were available as of November of 2020 were included in the current analysis. Weekly health questionnaires administered on all participants regardless of treatment assignments were collected before and during the COVID‐19 pandemic. Low mood (“Blueness”) was self‐reported as feeling downhearted or blue for three or more days in the past week (YES/NO). Social contacts were self‐reported by amount of time they had interacted, with whom (family; friends; others), and via which modalities (in‐person; phone/video call; text/email).

Result

A total of 4,774 weeks of survey data were analyzed (3,047 before COVID 19). The weekly average time spent in‐person, on phone/video call, and via text/email were 282, 113, and 44 minutes, respectively. During the COVID‐19 pandemic, participants on average spent 82 minutes less in total social contact per week (in‐person: reduced 123 minutes, video/call: increased 28 minutes, text/email: increased 13 minutes per week). Generalized estimating equation model revealed that in‐person family contact was associated with less blueness regardless of the pandemic (OR=0.91, p=0.04). There was a COVID*text/email time with friends interaction (OR=0.68, p=0.03), suggesting that during the COVID‐19 pandemic, an increase of 1 hour of texting/emailing with friends per week was associated with 32% decrease in experiencing blueness three or more days per week.

Conclusion

In‐person family time is beneficial for mental health. While in‐person contacts become less frequent during the COVID‐19 pandemic, increased text/email time with friends becomes an alternative to maintain mental health for socially isolated older adults.
Distinct cognitive and neuropsychiatric features of amnestic dementia with comorbid Alzheimer’s and TDP‐43 proteinopathies
Authors: Kochheiser Makayla L , Kawles Allegra , Minogue Grace , Keszycki Rachel M. , Riley Michaela , Mao Qinwen , Flanagan Margaret E , Mesulam Marsel , Geula Changiz , Weintraub Sandra , Gefen Tamar
Published: December 2021

Background

Inclusions containing phosphorylated transactive response DNA‐binding protein 43 (TDP‐43) aggregates have been shown to coexist in ∼60% of cases with postmortem Alzheimer’s disease (AD) pathology, typically confined to mediotemporal brain regions. Together, these comorbid proteinopathies (TDP/AD) can lead to an amnestic dementia syndrome. The goal of this study was to identify, at early symptom onset, the shared versus distinct clinical, neuropsychological, and psychiatric features of cases with amnestic dementia and comorbid TDP/AD compared to those with AD as the primary neuropathologic diagnosis.

Method

Twenty‐six individuals with amnestic impairment (Memory CDR=0.5 or 1) were identified from the Northwestern Alzheimer’s Disease Research Center and stratified by the presence of either postmortem AD pathology (N=13) or comorbid TDP/AD (N=13). Neuropsychological scores from tests of attention, language, executive functioning, visuoconstructional abilities, and mood/neuropsychiatric symptoms were analyzed from the NIA’s Uniform Data Set, version 2.0 or 3.0. Verbal (narrative and list‐learning) encoding and recall, and visual recall were included in memory assessment. In a subset of cases, a “visual‐to‐verbal” recall score was computed to determine the relative strength of visual memory compared to verbal. Student t‐tests with Welch’s correction were used to determine differences between groups.

Result

There were no differences in age at onset or death, frequency of APOE‐4 allele, or years of education between clinical groups. Preliminary findings showed no differences in attentional, executive, language, or visuoconstructional abilities. However, at disease onset, the TDP/AD group showed substantially higher frequency and severity of neuropsychiatric symptoms, including depression (p<0.005). Memory testing showed no group differences at the levels of learning/encoding verbal information; however, the TDP/AD group performed significantly worse in long‐term recall for narrative information (p<0.05). Qualitatively, the TDP/AD group showed stronger visual recall abilities (relative to verbal), whereas the AD group showed comparable performances in recall of material‐specific information.

Conclusion

Preliminary findings suggest that comorbid TDP/AD underlying amnestic impairments demonstrate a distinct cognitive and neuropsychiatric phenotype at disease onset. These findings help lay the groundwork for future in‐depth clinicopathologic studies and can help guide proper diagnosis of multiple etiology amnestic dementia.
Depressive symptoms in cognitively unimpaired older adults are associated with decreased structural and functional integrity in the limbic network
Authors: Touron Edelweiss , Moulinet Inès , Kuhn Elizabeth , Sherif Siya , Ourry Valentin , Landeau Brigitte , Mézenge Florence , Vivien Denis , Klimecki Olga M , Poisnel Géraldine , Marchant Natalie L , Chetelat Gaël ,   the Alzheimer’s Disease Neuroimaging Initiative,   the Medit‐Ageing Research Group
Published: December 2021

Background

Subclinical depressive symptoms are prevalent in older adults. They are associated with increased risk for both clinical depression and Alzheimer’s disease (AD), and may at least partly reflect early AD manifestations. However, the brain mechanisms underlying the relationship between depressive symptoms and AD remain to be elucidated. The aim of this study was to provide a comprehensive overview of the brain substrates of subclinical depressive symptoms in cognitively unimpaired older adults using complementary multimodal neuroimaging data in two independent cohorts.

Method

We selected 135 cognitively unimpaired older adults from the baseline data of the primary cohort Age‐Well, and 252 from the replication cohort ADNI. In both cohorts, subclinical depressive symptoms were assessed using the 15‐item version of the Geriatric Depression Scale (GDS); based on this scale, participants were classified as having depressive symptoms (DepS; GDS > 0) or not (NoDepS; GDS = 0). Voxelwise between‐group comparisons were performed to highlight differences in gray matter volume and amyloid deposition (both cohorts), as well as white matter integrity, brain perfusion (Age‐Well) and glucose metabolism (ADNI). Analyses were corrected for age, sex and education (and anxiety when available i.e. in Age‐Well) and thresholded at p<0.005.

Result

Older adults with subclinical depressive symptoms had significantly lower gray matter volume, perfusion and glucose metabolism in the hippocampus compared to participants without symptoms (Fig. 1). Glucose hypometabolism extended to the amygdala, precuneus/posterior cingulate and medial prefrontal cortex, insula, and temporoparietal cortex. Older adults with subclinical depressive symptoms also showed lower white matter integrity in the fornix and the posterior parts of the cingulum and corpus callosum. Brain amyloid deposition was not associated with the presence of subclinical depressive symptoms in either cohort.

Conclusion

The presence of subclinical depressive symptoms in cognitively unimpaired older adults are associated with brain structural and functional changes in regions of the limbic network known to be particularly vulnerable to AD. Structural and functional changes overlapped in the hippocampus, indicating that deterioration in this region could underlie the relationship between depressive symptoms and AD while amyloid deposition does not appear to be involved at this stage.
Caspase activation and inflammation observed in the olfactory bulb of APOE4 transgenic mice
Authors: AlOtaibi Majed , Lessard‐Beaudoin Mélissa , Gonzales Laura M. , Chouinard‐Watkins Raphaël , Plourde Melanie , Calon Frederic , Graham Rona
Published: December 2021

Background

Alzheimer disease (AD) is a chronic neurodegenerative disorder that affects millions of individuals worldwide. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may lead to the discovery of biomarkers and/or treatments for neurodegenerative diseases. Objectives: To characterize the olfactory system in a murine model expressing a genetic risk factor for AD. We investigated olfactory brain region atrophy as well as caspase expression and tissue inflammation in the APOE4 mouse model of AD.

Method

We assessed the olfactory system in 12 month old wild type (WT) and APOE4 olfactory bulb (OB) for atrophy, caspase activation, markers of neurogenesis and inflammation. We used Western blotting, RT‐PCR and immunohistochemistry.

Result

There was a significant decrease in OB bulb weight in APOE4 mice compared to WT (p<0.01). There was a significant increase in the full length (p<0.05) form of caspase‐8 and in the p30 fragment (p<0.05) in the APOE4 OB. Moreover, a trend increase in caspase‐8 mRNA (p=0.08) and significant increase in caspase‐9 mRNA in the APOE4 OB vs. WT. Furthermore, there was a decrease in the expression of the mature neuronal marker NeuN in the OB of the APOE4 mice compared to WT. This was with both the 46kDa (p<0.05) and 48kDa (p<0.05) isoforms of NeuN. As atrophy was observed in the APOE4 OB we then assessed for inflammation. Using the IBA‐1 marker for microglia demonstrated that there was a significant increase in IBA‐1 expression (p<0.01) and a trend increased in IBA‐1 positive cells (p=0.054) in the APOE4 OB compared to WT

Conclusion

These data suggest that there are alterations in neurogenesis in the OB of human APOE4 transgenic mice in addition to inflammation. This corresponds well with what has been observed in human AD brain tissue. Caspase activities detected may play a role in the inflammation observed. Studying the olfactory system in the aging population may help to discover biomarkers in the early stages of AD
Person‐centered care for family caregivers of people living with dementia: Co‐designing an education program for the healthcare workforce
Authors: Parmar Jasneet , Anderson Sharon Dorothy , Pollard Cheryl , Duggleby Wendy , Charles Lesley , Poole Lisa , Leslie Myles , McGhan Gwen , Huhn Arlene , Sereda Sandy , Marion Cecelia , Tarnowski Glenda , Mah Jennifer , Melenberg Denise , Weir Carolyn , Pooler Charlotte , Maclaughlin Nora , Brémault‐Phillips Suzette
Published: December 2021

Background

Recent research recommends the healthcare workforce receive competency‐based education to identify, assess, support and partner with family‐caregivers [FCGs} across the care trajectory.[1 2] Although the risk of FCG anxiety, burden, and loneliness to FCG’s wellbeing is widely documented, typically education has been targeted towards FCG’s to increase their care skills rather to educate healthcare providers to support FCG’s caregiving and wellbeing.[3]

Objectives

We will present the co‐design process used to create a competency‐based education program for the healthcare workforce that ensures a person‐centered focus on FCGs and introduce our Health Workforce Caregiver‐Centered Care Education focused on dementia. Co‐design is the act of creating with stakeholders to ensure the results meet their needs and are usable.

Project Description

We began by coining the concept “caregiver‐centered care,” defining it as: a collaborative working relationship between families and healthcare providers aimed at supporting FCGs in their caregiving role, decisions about services, care management, and advocacy [4 5]. From this definition, and working with multi‐level interdisciplinary stakeholders we designed[6] and validated[7] a Caregiver‐Centered Care Competency Framework in a Modified Delphi Process. Stakeholders (n= 101) including FCGs, health providers, policy makers, community organizations, research team, script writer, and educational designers then used effective practices for dementia education for the health workforce [8‐11] to co‐design the first or ‘foundational’ level of a Caregiver Centered Care education program.

Results

Teaching and learning resources include six competency‐aligned educational modules with videos and interactive exercises that encourage reflection. With the COVID‐19 pandemic, we moved the education online (caregivercare.ca). In the first two months online, November 9, 2020‐January 9, 2021, 352 healthcare providers completed the education. To date, learners’ qualitative evaluations have been positive, “Very good information for professionals working with caregivers; especially relevant to homecare, geriatricians, allied health, and others working within the Seniors’ Health realm. Engaging format that really evokes empathy for caregivers.”

Discussion

We continue to use mixed methods to evaluate the Caregiver‐Centered Care Education, for acceptability and effectiveness, in five care contexts (primary, acute, home, supportive living, long‐term care).

Conclusion

We expect that our education will support caregiver‐centered care in all settings providing dementia‐related care.
Person‐centered care for family caregivers of people living with dementia: Evaluating an education program for the healthcare workforce
Authors: Parmar Jasneet
Published: December 2021

Background

While family caregivers[FCGs] provide over 90% of care for people with dementia[1 2] most members of the healthcare workforce do not meaningfully involve FCGs as partners in care[3 4] or support FCGs in maintaining their own wellbeing. Recent research recommends the healthcare workforce receive competency‐based education to identify, assess, support and partner with FCGs across the care trajectory.[5 6] A multi‐level interdisciplinary team (n=101) co‐designed competency‐based person‐centered education for the health workforce. It is offered free online (caregivercare.ca)

Objectives

Report on a mixed methods evaluation of a person‐centered competency‐based education program for the healthcare workforce.

Project description

To create the program we began by coining the concept “caregiver‐centered care,” defining it as: a collaborative working relationship between families and healthcare providers aimed at supporting FCGs in their caregiving role, decisions about services, care management, and advocacy [7 8]. From this definition, multi‐level, interdisciplinary stakeholders including FCGs (n=101) co‐designed a first or ‘foundational’ level of a Caregiver‐Centered Care education program. Teaching and learning resources include six competency‐aligned educational modules with videos and interactive exercises that encourage reflection.

Methods

The Kirkpatrick Barr[9 10] health workforce training evaluation framework underpinned our mixed methods evaluation design. We used the Student Satisfaction with Education Scale to measure participant’s reaction to the education (Level 1) and the Caregiver‐Centered Care Knowledge Assessment Test [CKAT] to assess changes in learner’s knowledge and confidence to work with FCGs (Level 2).

Results

In the first two months 352 healthcare providers completed the education through caregivercare.ca. Learners were satisfied with the overall quality of education (Mean 4.69 (SD=.6) Median 5). Student’s paired samples T‐test indicates pre‐post education changes in knowledge and confidence to work with FCGs were significant. Pre (M=37.8, Sd=7.6) to post (M=47.2, SD=3.5) t (125) = ‐14.39, p<.0005 (two‐tailed). Qualitative results derived from open responses mirrored the quantitative results.

Discussion

Educating the health workforce is a population health approach to address known gaps in supporting and working with FCGs across the care trajectory[2 3 11].

Conclusion

The Care‐Giver Centered Care education provides a foundation for educating healthcare providers working with FCGs to provide person‐centered care to FCGs.
Another side of the coin: Primary progressive aphasia in Chinese language
Authors: Tee Boon Lead , Tempini Maria Luisa Gorno , Chen Ta‐Fu , Lo Raymond Y. , Wang Pei‐Ning , Chan Andrew LT , Chen Lorinda Li‐Ying Kwan , Wong Adrian , Yan Connie TY , Tsoh Joshua , Lu Chien Jung
Published: December 2021

Background

Primary Progressive Aphasia (PPA) is a neurodegenerative syndrome that presents with speech and language impairments and is generally classified into three variants: semantic (svPPA), nonfluent/ agrammatic (nfvPPA), and logopenic variants (lvPPA). Current understanding of PPA has been mostly derived from English language patients. Expanding PPA research into non‐English languages encourages language‐specific linguistic‐adapted assessments and enriches our knowledge in linguistic features distinct from English language. This presentation focuses on three Chinese linguistic features that differ from English language: lexical tones, classifier, and logographic script. Chinese is a tonal and classifier language in which tones are lexically contrastive, and classifiers are obligatory to quantify nouns numerally. It also adopts logographic script that has complex visuospatial configurations and weak grapheme‐phoneme correspondence.

Method

The CLAP (Chinese LanguageAssessment for PPA) battery is designed to characterize the neurolinguistics features of Chinese speaking PPA individuals. In CLAP classifier task, participants are asked to spontaneously produce classifiers specific to numerous nouns and presented with multiple choices when failed. To evaluate Chinese writing skills, participants are tasked with dictating 60 Chinese characters of varying lexicality, character frequency, and stroke number. The motor speech function is assessed by multiple repetitions of Chinese characters that differ in articulation places, manners, and tones.

Results

The CLAP project enrolled 20 controls and 33 PPA individuals (7 nfvPPA, 10 svPPA, and 16 lvPPA). In classifier task, svPPA and lvPPA scored lower (p<0.01), though lvPPA were more responsive to choices than svPPA (p<0.001). The classifier score significantly correlated with volumetric changes over the left middle, inferior temporal, and fusiform gyri, brain regions typically associated with semantic functions. For orthographic dictation task, all three PPA variants performed worse than controls (p<0.001), and distinctive dysgraphia phenotypes were noted in each variant (svPPA: phonological plausible and perseveration errors; nfvPPA: motoric, radical and morphemic errors; lvPPA: visual and stroke errors, P<0.001). In motor speech task, nfvPPA showed lower performance when tasked with repeating characters that vary in articulation places and tones (p=0.018, p<0.001) but not in articulation manners (p=0.076).

Conclusion

The clinical features and assessment strategies for PPA syndrome may vary across languages and should ideally be tailored linguistically.
Validity of online versus in‐clinic self‐reported Everyday Cognition Scale (ECog): Online measures performed as well as repeating the in‐clinic assessment
Authors: Howell Taylor , Neuhaus John , Glymour M Maria , Nosheny Rachel L , Weiner Mike W.
Published: December 2021

Background

Clinical assessment of cognition and functional abilities plays an important role in identifying individuals at risk for cognitive decline, mild cognitive impairment (MCI), and dementia due to Alzheimer’s (AD). In‐person clinical assessments can be logistically challenging and deter broad participation in clinical studies, reducing diversity in AD research. Online assessments are an appealing alternative, but the validity of online compared to clinical in‐person assessments has not been established. Our goal was to determine whether the Everyday Cognition (ECog) Scale, which assesses decline in instrumental activities of daily living, collected online corresponds well with ECog collected in‐clinic. The correspondence of in‐clinic and online measures could not logically exceed the test‐retest reliability of the in‐clinic measure, so we used this as a benchmark for validity of the online measure.

Method

Self‐reported ECog was collected both in‐clinic and online from 94 older adults (characteristics described in Table 1) enrolled in both the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Brain Health Registry (BHR). Associations between in‐clinic and online ECog scores were estimated using linear regression. Prediction error was corrected for optimism with 10‐fold cross‐validation. We estimated test‐retest reliability of in‐clinic ECog in 259 cognitively normal ADNI2 participants (characteristics described in Table 2) with two in‐clinic ECog measures, completed six months apart. Reliability was estimated using the intraclass correlation coefficient (ICC) and linear regression. Age, gender, education, and time between assessments were included as covariates in all regression models.

Result

(1) Validity of online ECog. Mean online ECog scores were significantly associated with mean in‐clinic ECog scores (β=0.81, 95% CI 0.64‐0.98, p=0.00). The optimism‐corrected R2 was 0.61 (95% CI 0.40‐0.82). (2) Reliability of In‐clinic ECog: The ICC was estimated to be 0.67 (95% CI 0.54‐0.79). Mean in‐clinic ECog scores collected at 6 months were significantly associated with in‐clinic ECog score collected at baseline (β=0.71, 95% CI 0.63‐0.78, p=0.00). The optimism‐corrected R2 was 0.61 (95% CI 0.51‐0.72).

Conclusion

The online ECog corresponded well with in‐clinic ECog and provided as much information as repeating the in‐clinic ECog. This supports the validity of online ECog, a measure of functional and cognitive decline.
The development and validation of a new cross‐cultural naming test
Authors: Franzen Sanne , Satoer Djaina , van den Berg Esther , Papma Janne M.
Published: December 2021

Background

Traditional naming tests such as the Boston Naming Test are unsuitable to assess naming impairment in diverse populations, given the large influence of culture, language, and education on performance. A more fair naming test is urgently needed. The goal of this study was therefore to develop and validate a new cross‐cultural naming test to diagnose naming impairment in Alzheimer’s disease in diverse populations.

Method

We carried out a multistage pilot study. First, we generated a list of 149 potentially cross‐cultural items, and selected the items with a homogeneous age of acquisition and word frequency across multiple languages. For the 74 items that remained, we selected several colored photographs (examples provided in Figure 1), out of which 194 controls selected the best matching photograph. The 74‐item test was piloted in 15 diverse healthy controls, after which 14 items were removed. The final 60‐item test was validated in 39 controls and 61 culturally, educationally, and linguistically diverse patients – mainly with dementia (30%), psychiatric illness (20%), MCI (16%), or subjective memory impairment (15%). Participants were mostly from North Africa, Suriname, Eastern Europe, and the Middle East, and the majority of participants had an education level of primary school or lower (51%).

Result

The new cross‐cultural naming test was well able to discriminate between patients with Alzheimer’s/mixed dementia (n=11, median score: 48/60) and the rest of the sample (median: 58/60, AUC=0.87). Preliminary item analyses indicated that colors, as well as animals (ant, worm, snake) and occupations with a later age of acquisition/lower word frequency were the most sensitive. There were robust correlations with other measures of language (Recall of Pictures Test naming ρ=0.26, p=.04, animal fluency ρ=0.66, p<.001, foods fluency ρ=0.57, p<.001), as well as a culture‐sensitive cognitive screener (ρ=0.69, p<.001). The scores were not correlated with education level, age, or number of years of residence in the Netherlands (analysis in controls).

Conclusion

This new naming test is an important step towards a more fair neuropsychological assessment and more accurate dementia diagnosis in culturally, linguistically, and educationally diverse individuals.