bluuebunny/crossref_metadata_2025 huggingface dataset:
Adapting to the COVID‐19 pandemic in cohort studies: Validation of online assessments of cognition and neuropsychiatric symptoms in an aging population
Authors: Lussier Firoza Z , Servaes Stijn , Kang Min Su , Bezgin Gleb , Chamoun Mira , Stevenson Jenna , Rahmouni Nesrine , Stevenson Alyssa , Pascoal Tharick A. , King Suzanne , Bzdok Danilo , Gauthier Serge , Rosa‐Neto Pedro
Published: December 2021

Background

The occurrence of the COVID‐19 pandemic has had a significant impact on cohort studies, particularly those whose subjects are at higher risk of developing complications from the virus. As such, assessment methods must be adapted to minimize COVID‐19 exposure risk. The TRIAD (Translational Biomarkers of Aging and Dementia) cohort assessed N=292 individuals during initial COVID‐19 lockdown measures by telephone interview to rate cognition, neuropsychiatric symptoms, and impact of the pandemic. To increase speed and efficiency of data collection, we aim to follow these individuals by means of online survey. Here, we present a validation of our online assessment tools by comparing data obtained through both methods (phone interview and online survey) in the same subjects.

Methods

10 subjects (4 elderly CN/3 MCI/3 AD) and their informants participated in this study. Subjects were varied for assessment language (English/French) and first assessment method (phone/online). 18 instruments were administered (listed in Table 1). Instrument scores were first compared by computing individual differences (phone‐online), then by pooling all scores by assessment type and calculating an effect size. Pearson correlation coefficient between phone and online scores was also computed.

Results

Mean interval between assessments was 8.8±4.8 days. Mean length of online assessment (63.7±20.7mins) was comparable to mean phone interview length (72.6±32.4mins). Instrument scores from phone interviews had a total mean of 102.60, while scores from online surveys had a total mean of 103.93, with a pooled SD of 716.09. Effect size was ‐0.00186. Correlation of phone and online scores yielded a Pearson’s R of 0.85 (p<0.05). Pearson’s R was also computed by applying bootstrapping using 1000 resamples without replacement with a sample size of 50. The Pearson R coefficient after bootstrapping was 0.91 (95% CI: [0.7699‐0.998]).

Conclusion

Our results suggest that instrument scores from phone and online assessments are comparable, and not significantly different from each other. The observed variance in scores between phone and online assessments may be due in part to the normal test‐retest variability associated with re‐administering instruments. This validation of online assessment tools in an aging population is of significant importance to human studies in the context of COVID‐19.
Associations of neuropsychiatric symptoms with cognitive impairment: The utility of the mild behavioral impairment checklist and the neuropsychiatric interview questionnaire in a cognitive neurology clinic population
Authors: Hu Sophie , Patten Scott B , Charlton Anna , Fischer Karyn , Fick Gordon , Smith Eric E. , Ismail Zahinoor
Published: December 2021

Background

Mild Behavioral Impairment is characterized by later life emergent and persistent neuropsychiatric symptoms (NPS). MBI domains include impaired drive/motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and psychosis. We aimed to compare the relationship between NPS and cognition in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and dementia, using the Mild Behavioral Impairment‐Checklist (MBI‐C) and Neuropsychiatric Inventory Questionnaire (NPI‐Q). MBI domains were derived from the NPI‐Q using a published algorithm.

Method

Data was examined from 1238 patients in the PROMPT Cognitive Neurology Clinic registry at the University of Calgary. NPS were characterized at baseline using the MBI‐C (n=474) and NPI‐Q (n=1040). Forward stepwise linear regression models were conducted to compare MBI‐C and NPI‐Q total and domain scores with cognition as assessed using the Montreal Cognitive Assessment (MoCA). Age, diagnosis, sex and education were included as covariates.

Result

Overall, 90% of patients had an MBI‐C total score>0 and 55.91% of patients scored above cutoff (>7). MBI prevalence (based on cutoff) was 37% in patients with SCD, 54% in MCI, and 62% of dementia patients scored above the cutoff. By domain, over half had impaired drive/motivation (59.57%), affective dysregulation (68.66%) or impulse dyscontrol (64.11%), while relatively fewer had social inappropriateness (33.97%) or psychotic symptoms (22.25%). For the NPI‐Q, 67.98% of patients had a total score>0 including 60.36% of SCD, 60.00% of MCI and 74.95% of dementia. By domain, over half had affective dysregulation (61%) or impulse dyscontrol (58.50%) while less than half had impaired drive/motivation (44.31%), social inappropriateness (23.19%) or psychosis (10.18%). With increasing diagnostic severity, age, MBI‐C and NPI‐Q scores increased, while MoCA scores decreased. Greater MBI‐C and NPI‐Q total and domain scores were significantly associated with lower MoCA score. Of all domains, psychosis had the strongest association with impaired cognition using both measures. Age, sex and diagnosis were modifiers for the MBI‐C.

Conclusion

NPS are associated with poorer cognition regardless of diagnostic status. MBI domain scores are more strongly associated with impaired cognition than total scores. These findings suggest that the MBI‐C has utility in capturing NPS in this specialty clinic population, as a complement to the NPI‐Q.
Blood pressure trajectories from early life and their association with cognitive function changes in midlife
Authors: De Anda‐Duran Ileana , Fernandez‐Alonso Camilo , Carmichael Owen T , Au Rhoda , Bazzano Lydia , Kolachalama Vijaya B
Published: December 2021

Background

Hypertension (HTN) is a well‐established risk factor for cognitive impairment and dementia. HTN‐induced vascular endothelium and smooth muscle damage have been described as pivotal components of the pathophysiological cascade over the life‐course. While the impact on cognitive function (CF) changes has been studied from midlife‐ to old age, the impact from childhood to middle age exposure remains poorly understood. We aimed to explore this relationship in a community‐based cohort of middle‐age adults.

Methods

The analysis included a total of 342 adult participants (67.3% Woman, 38.9% African American) from the Bogalusa Heart Study, with CF assessments at two time points, baseline (age 48.8 ± 4.9 years) and follow‐up (age 51.7 ± 5.2 years), and at least 3 observations of BP since childhood. CF change was assessed by computing the difference of the two timepoints standardized global cognitive score (GCS) obtained from a battery of tests covering major neuropsychological domains. Systolic BP (SBP) trajectories were created using latent class trajectory modeling. Mixed linear models with unstructured covariance were used to determine the association between SBP trajectories and CF changes in midlife.

Results

Mean CF assessment follow‐up was 2.9 ± 0.6 years, and mean follow‐up for BP and other traditional cardiovascular (CV) risk factors was 41.8 ± 3.4 years. Three distinct trajectory classes of SBP were identified: increasing to plateau (n=226 [66.1%]), moderate‐ (n=54 [15.8%]) and high‐ (n=62 [18.1%]) increasing (see Figure 1). With the increasing to plateau SBP trajectory as reference, and after adjustment for modifiable dementia risk factors and traditional CV risk factors, the high‐increasing SBP trajectory was associated with greater decrease in GCS (β= ‐1.22 [95%CI ‐2.39, ‐0.07]; p=0.038). The moderate‐increasing SBP trajectory showed no statistically significant association with GCS change (β= ‐1.00 [95%CI ‐2.23, ‐ 0.22]; p=0.109). (see Table 1)

Conclusions

These findings suggest that highly‐increasing SBP trajectories over time, particularly from childhood to mid‐ life, may adversely affect cognitive performance in midlife, independent of modifiable dementia risk factors. This underscores the importance of addressing CV risk factors during childhood and adolescence through primary prevention, as their cumulative burden could have a detrimental impact on brain health.
Association of tau pathology and vascular risk factor burden with longitudinal measures of plasma neurofilament light
Authors: Ferrari‐Souza João Pedro , Brum Wagner Scheeren , Hauschild Lucas Augusto , das Ros Lucas U. , Bieger Andrei , Ferreira Pamela C.L. , Bellaver Bruna , Benedet Andréa Lessa , Therriault Joseph , Rosa‐Neto Pedro , Karikari Thomas K , Pascoal Tharick A. , Zimmer Eduardo R.
Published: December 2021

Background

In the context of Alzheimer’s disease (AD), tau pathology is a major driver of the neurodegenerative cascade that ultimately leads to loss of neurons and synapses. In fact, studies have shown that neurodegeneration is more strongly associated with tau pathology than amyloid‐β (Aβ) accumulation. Although plasma neurofilament light (NfL) is a neuroaxonal damage biomarker that currently is in the research spotlight, the factors influencing the association between its longitudinal trajectory and tau pathology remains unclear. Since vascular risk factors (VRFs) present an important role in AD etiology and progression, here we aimed to determine whether tau pathology, in combination with or independently of VRF burden, is associated with longitudinal plasma NfL trajectory.

Method

We assessed 901 participants [276 CU, 455 MCI and 170 AD] from ADNI with baseline plasma p‐tau181 and [18F]AV45 Aβ‐PET, as well as longitudinal plasma NfL measurements (up to 4 years). Baseline VRF burden was calculated considering the history for cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, stroke or transient ischemic attack, smoking, atrial fibrillation and left ventricular hypertrophy. Individuals were dichotomized as following: elevated VRF burden if ≥2 VRFs (V+), tau positive if plasma p‐tau181 ≥ 17.7 pg/mL (T+) and amyloid positive if global Aβ‐PET SUVR ≥ 1.11 (A+). Subjects who were A‐T+ were excluded. Linear mixed‐effects models (LMMs) were performed to evaluate plasma NfL’s longitudinal trajectories.

Result

The LMMs demonstrated that tau positivity (T+) was significantly associated with a higher rate of longitudinal increase in plasma NfL levels in comparison to the tau‐negative group (Fig. 1). However, analysis dividing the groups both by tau and VRF burden status demonstrated that the rates of increase in plasma NfL were greater only in the presence of both VRF burden and tau positivity (T+V+; t‐value=2.54, p<0.05), when compared to the reference group (T‐V‐; Fig. 2). Moreover, specific slope‐contrast analyses confirmed that only the T+V+ group presented a clearly separate trajectory.

Conclusion

Our findings suggest that an elevated VRF burden influences the relation between tau pathology and neurodegeneration in AD.Therefore, tau‐mediated neurodegeneration seems to be most relevant in combination with vascular‐mediated neuroaxonal injury. These findings reinforce the pivotal contribution of vascular pathology to AD development.
Difference in allostatic interoceptive network connectivity by cognitive status
Authors: Bateman James R. , Kawas Mohammad I , Craft Suzanne , Lockhart Samuel N. , Kim Jeongchul , Sai Kiran K Solingapuram , Lindquist Kristen A , Whitlow Christopher T.
Published: December 2021

Background

The allostatic interoceptive network (AIN) has been proposed as central to linking interoceptive processing and autonomic regulation and involved in emotional experience. Early pathologic changes in AD occur in hubs of the AIN, and changes in emotional reactivity have been identified at both the MCI and dementia stages of Alzheimer’s disease. Interoception has been proposed as a core feature in psychiatric disease, though relatively little attention has been paid to altered interoception in neuropsychiatric symptoms in dementia. We conducted a pilot analysis in cognitively normal (CN) participants and those with mild cognitive impairment (MCI) to identify alterations in functional connectivity of the AIN, default mode, and salience networks.

Method

Twenty‐two participants from the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort including CN participants (n = 11, mean age = 67 ± 7) and MCI (n = 11, mean age = 72 ± 7) received 3T brain MRI using T1 for gray/white matter segmentation and BOLD for resting‐state functional connectivity. BOLD time series data were pre‐processed and de‐noised using standard techniques. Connectivity analyses were performed using the CONN functional connectivity toolbox. Briefly, we performed a comparison of within‐network connectivity of the allostasis and interoception system (comprised of the DMN, SN, and AIN seed regions) between MCI and NC participants while adjusting for age (p < 0.05 uncorrected).

Result

Table lists the baseline demographic and clinical characteristics for CN and MCI groups. Participants with MCI had greater connectivity between limbic regions of the AIN and salience network compared with the CN group, and decreased connectivity between the left lateral parietal cortex and multiple hubs of the salience network. Within the AIN seed regions, the amygdala and dorsal posterior and mid insula had increased connectivity (Figure; p < 0.05 uncorrected).

Conclusion

We find differences in functional connectivity between CN adults and persons with MCI for three brain networks. Our analyses provide preliminary support that changes in an integrated allostasis and interoceptive system, integrating components of the DMN and SN, may have implications for emotional dysregulation in ADRD.
A nuanced portrait of how race/ethnicity and nativity influence cognitive trajectories among older adults in the United States
Authors: Garcia Marc A , Tarraf Wassim
Published: December 2021

Background

Cognitive decline and Alzheimer Disease and Related Dementias (ADRDs) represent significant public health challenges that affect the quality of life and independence of older adults. Previous research documents large racial/ethnic disparities in cognition; However, less is known about variation in cognitive functioning trajectories within minority populations, specifically among older Latinos. Understanding how demographic and socioeconomic factors influence cognitive health in later life is particularly important given the rapidly growing and diversifying United States population.

Method

We use 18‐years of biennial Health and Retirement Study data (1998‐2016) to estimate Generalized Estimating Equations (GEE) modeling sex specific age graded changes in global cognition and memory (based on Modified Telephone Interview for Cognitive Status) among White, Black, and U.S.‐ and foreign‐born Latino adults aged 51 years and older.

Result

Adjusting for socioeconomic factors, health behaviors, and chronic health conditions, we find consistent evidence for curvilinear (quadratic) associations between age and cognitive change across race/ethnic and nativity groups (bage=028; SE=0.010; p<0.01 and bage2=‐0.005; SE<0.0001; pp<0.0001), regardless of sex. Among males, racial/ethnic and nativity differences in cognitive function were mainly evident at younger ages, particularly for Blacks compared to Whites (see Figure below). We found no evidence to support male racial/ethnic or nativity differentials in trajectories of cognitive aging. For women, older Black and US‐Born Latina adults, and to a lesser degree foreign‐born Latinas, had lower cognitive function at younger ages (see Figure). Moreover, White women showed more pronounced cognitive aging in comparison to U.S.‐ and foreign‐born Latinas (see Figure). These results were consistent for both global and memory specific outcomes.

Conclusion

Our findings support current calls for more nuanced considerations of racial/ethnic and nativity effects on cognitive aging and ADRDs. Understanding minority and immigrant differences in cognitive decline has implications for assessing the burden of cognitive disease and the development and implementation of culturally‐appropriate programs to promote healthy brain aging.
Age at menopause relates to later‐life hippocampal volume in an APOE4‐specific manner
Authors: Sundermann Erin E , Saelzler Ursula G , Jacobs Emily Goard , Banks Sarah J , Shadyab Aladdin H , Taylor Caitlin M , Gleason Carey E , James Taryn T , Jonaitis Erin M , Panizzon Matthew S
Published: December 2021

Background

There are important sex differences in Alzheimer’s disease (AD) including two‐fold higher prevalence and stronger association of the apolipoprotien‐ε e4 allele (APOE4) with AD risk in women versus men. Given the central role of sex hormones in brain structure/function, examining factors influencing lifetime exposure to sex hormones is critical to understanding sex differences in AD. Menopause is characterized by a marked reduction in ovarian hormones, leading to loss of sex hormone‐related neuroprotective effects and AD‐like changes in brain bioenergetics. Earlier age at menopause is associated with higher AD risk; however, the brain mechanisms by which menopausal age contributes to AD etiology and the role of APOE4 in this association are unclear. Among non‐demented, older female participants of the Wisconsin Registry for Alzheimer’s Prevention (WRAP) cohort, we examined the associations of age at menopause with later‐life hippocampal and whole brain volumes and the moderating role of APOE4 in these associations.

Method

177 postmenopausal women ≥ 60 years of age (age range:60–76, age mean=65.8, 96% White) with MRI volumetric data and APOE4 genotype data were examined. Multivariable linear regressions were used to examine associations of self‐reported age at menopause and its interaction with APOE4 carrier status with hippocampal and whole‐brain volumes. Models were adjusted for intracranial volume, MRI scanner, age, education, BMI at MRI, smoking, age at menarche, number of pregnancies, natural versus surgical menopause and ever‐use of hormone therapy or hormonal contraception.

Result

A significant age at menopause × APOE4 interaction on hippocampal volume (p=.05) revealed that earlier age at menopause related to smaller hippocampal volume (p=.016) among APOE4 carriers but not non‐carriers (p=.86; Figure 1). Age at menopause did not relate to whole brain volume regardless of APOE4 status. In the multivariable model, older age, less education and smaller intracranial volume also related to smaller hippocampal volume.

Conclusion

Results suggest that early menopause may be a risk factor for neurodegeneration among APOE4 carriers particularly in the AD‐sensitive hippocampus. The specificity of this relationship to APOE4 carriers indicates mechanistic interactions between APOE4 and sex hormones and offers a potential contributing factor to the more adverse effect of APOE4 in women.
Identifying obstructive sleep apnea in geriatric outpatients with neuropsychological testing
Authors: Przybelski Anna Gabriel , Irwin Alissa M , Rumble Meredith E , Jones Jana , Plante David T , Przybelski Robert J
Published: December 2021

Background

Obstructive sleep apnea (OSA) is common in geriatric patients and has been associated with neurocognitive disorders such as Alzheimer’s disease and other dementias. Dexter and Ebert (2019) reported a unique pattern of lower scores for immediate memory relative to delayed memory was observed in patients with OSA on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The aim of the current investigation was to examine the frequency of confirmed OSA diagnosis in persons with snoring and immediate memory scores less than delayed memory scores in ambulatory geriatric patients referred for memory assessment.

Method

Patients were initially assessed for memory complaints at the University of Wisconsin‐Madison Geriatric Memory Assessment Clinic (2016 ‐2020). All patients completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Randolph, 1998, 2012) as part of a multidisciplinary evaluation. Patients were referred for a sleep evaluation if sleep disordered breathing was reported and the score difference was noted with immediate memory being less than delayed memory on RBANS. Sleep evaluations consisted of either home sleep testing or polysomnography, based on clinical indication. Board‐certified sleep medicine physicians interpreted all sleep studies, and graded the severity of OSA as mild, moderate, or severe.

Result

Results are depicted in Table 1. There were 251 patients referred for sleep evaluation (mean age 75.5 years). Of these, 158 patients completed sleep testing (93 males; 65 females), of which 127 (80.4%) were ultimately diagnosed with OSA. Among sleep study completers, 72 (57%) had moderate or worse sleep apnea. The proportion of cases with moderate or worse sleep apnea was similar for male (59%) and female (53%) completers.

Conclusion

This retrospective investigation involved geriatric memory clinic patients with RBANS scores that were lower in immediate memory compared to delayed memory and evidence of snoring that resulted in a referral for a sleep study. The finding of OSA in 80% of the patients evaluated, and the comparable results of male and female patients suggests that all patients who snore and have this unique RBANS profile should be assessed for OSA.
Cognitive, neuropsychiatric and imaging comparisons between early‐onset and late‐onset Alzheimer’s disease participants from LEADS and ADNI3
Authors: Apostolova Liana G. , Eloyan Ani , Gao Sujuan , Iaccarino Leonardo , Touroutoglou Alexandra , Aisen Paul S , Beckett Laurel , Borowski Bret J , Donohue Michael C , Fagan Anne M , Foroud Tatiana M. , Gatsonis Constantine , Jack Clifford R. , Kramer Joel H , Koeppe Robert A. , Saykin Andrew J. , Toga Arthur W. , Vemuri Prashanthi , Day Gregory S , Graff‐Radford Neill R. , Honig Lawrence S , Jones David T. , Masdeu Joseph C , Mendez Mario , Onyike Chiadi U , Rogalski Emily J , Salloway Stephen P. , Wolk David A. , Wingo Thomas S. , Carrillo Maria C. , Rabinovici Gil D. , Dickerson Brad C.
Published: December 2021

Background

The overarching goal of the Longitudinal Early‐onset Alzheimer Disease study (LEADS) is to optimally characterize early‐onset AD (EOAD) and establish an EOAD clinical trials network. Here we report the baseline demographic and imaging biomarker comparisons of the LEADS cohort to late‐onset AD (LOAD) subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI3).

Method

123 amyloid‐positive EOAD, 47 amyloid‐negative EOnonAD, 60 cognitively normal young controls were compared to 130 amyloid‐positive LOAD, 110 amyloid‐negative LOnonAD and 286 amyloid‐negative cognitively normal older controls. To account for the effect of cognitive aging between EO and LO populations, each cognitive measure was Z‐transformed. Cortical and hippocampal atrophy were quantified using W‐scores adjusted for age, sex and total intracranial volume. Z‐scores and W‐scores were compared using t‐test or Wilcoxson rank test as appropriate. All p‐values were corrected for multiple comparisons using the false discovery rate correction.

Result

EOAD showed greater pathology burden and greater cortical atrophy (AD signature) relative to LOAD. EOAD also showed greater cognitive impairment across all cognitive tests. EOAD showed greater functional impairment, more depression but less neuropsychiatric behaviors overall compared to LOAD (Table 1 and Figure 1, all ps<0.05). Repeating the analyses stratified by cognitive stage (MCI/dementia) or CDR global rating (0.5/1) did not result in any major differences.

EOnonAD differed from LOnonAD by also showing greater impairment on all cognitive and functional measures There were no significant differences in amyloid and tau burden, or atrophy W‐scores between these groups. EOnonAD were more depressed and showed more functional impairment compared to LOnonAD (Table 2 and Figure 2, all ps<0.05). Repeating the analyses split by cognitive stage (MCI/dementia) or CDR global rating (0.5/1) did not result in any major differences.

Conclusion

Consistent with our preexisting hypotheses, EOAD and EOnonAD perform much worse relative to their LO counterparts. EOAD also show greater pathological burden as expected. The reported analyses were done in chronological rather than disease time (time since disease onset). Benchmarking individuals along the disease spectrum might prove to be a better strategy especially when conducting analyses on rate of disease progression.
Cancer is inversely related to Alzheimer’s disease dementia independent of amyloid and tau
Authors: Kapoor Arunima , Nation Daniel A. ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2021

Background

Emerging evidence suggests an inverse relationship and common biological mechanism between cancer and Alzheimer’s disease (AD), with reduced risk of cancer among individuals with AD and reduced risk of AD among cancer survivors. Yet, few prior studies have explored the shared mechanism between the two diseases and examined whether amyloid and tau differ among cancer survivors.

Method

Participants included community‐dwelling older adults (age range 55‐90 years, M = 74.9 years; SD = 6.7; 52.4% male) from the Alzheimer's Disease Neuroimaging Initiative, who were cognitively normal (CN) or had AD at baseline assessment (N = 756). Cancer history was obtained from participant’s medical history. Lumbar puncture was performed to determine cerebrospinal fluid levels of phosphorylated tau (p‐tau), total tau (t‐tau), and β‐amyloid 1‐42 (Aβ1‐42). Prevalence of cancer history and CSF levels of AD pathology biomarkers in those with and without history of cancer were examined in the CN and AD groups.

Result

A total of 176 (23.3%) patients had history of cancer. Patients with history of cancer were older (M = 76.5, SD = 6.7) compared to those without (M = 74.4, SD = 6.7, p <. 001) and more likely to be male (62.5% vs. 49.3%, p = .002). Those with AD were significantly less likely to have history of cancer compared to CN (36.9% vs. 63.1%, χ2(1) = 5.8, p = .016). Among those with AD, there was no significant difference in p‐tau, t‐tau and β‐amyloid levels between those with history of cancer compared to no history. Similarly, p‐tau, t‐tau and β‐amyloid levels did not differ between those with or without history of cancer in CN.

Conclusion

Consistent with previous studies, we observed a lower incidence of cancer in individuals with AD compared to CN. However, we observed no difference in levels of traditional AD pathology biomarkers, suggesting the shared mechanism between cancer and AD may not be driven by β‐amyloid and tau. Alternative mechanisms, such as angiogenesis, are known to play a key role in both diseases and future studies are warranted to explore the role of vascular contributions to improve our understanding of the pathophysiology of both AD and cancer.
Education, white matter hyperintensities, and cognition in diverse cohorts of older adults
Authors: Eng Chloe W , Gilsanz Paola , Fletcher Evan M , Kornak John , George Kristen M , DeCarli Charles S , Barnes Lisa L , Glymour Maria M , Whitmer Rachel A
Published: December 2021

Background

Higher education predicts better late‐life cognition among older adults, but mechanisms are poorly understood. We examined whether education modified the pathway between vascular injury and late‐life cognition.

Method

Analyses pooled imaging data from the multiethnic Kaiser Healthy Aging and Diverse Life Experience Study (KHANDLE; n=219) and the Study of Healthy Aging in African Americans (STAR; n=132), two parallel studies of older adult long‐term Kaiser Permanente members. Self‐reported education was considered as continuous years of completed education. White matter hyperintensities (WMH) were obtained through 3T MRI. Cerebral WMH volume to total cerebral volume ratio was log transformed and regressed on age; residuals were z‐standardized for measure of age‐adjusted WMH volume. Cognitive domains of verbal episodic memory (VRMEM), semantic memory (SEM), and executive function (EF) were measured using the Spanish and English Neuropsychological Assessment Scales (SENAS) and z‐standardized. Domain‐stratified regression models examined (1) independent effect of WMH adjusting for education, and (2) effect modification by education on the relationship between WMH and cognition. All models were adjusted for age, race/ethnicity, gender, and study.

Result

Participants were on average 73.2 years of age with 14.7 years of education, with 57.8% of the sample identifying as female and 49% of the sample identifying as Black. Education was significantly associated with all late‐life cognitive domains but for WMH volume (B: ‐0.02, 95% CI: ‐0.06, 0.02, p‐value: 0.38). In models adjusting for education and all covariates, effect of WMH on cognition was largest for EF (B: ‐0.09, 95% CI: ‐0.17, ‐0.01, p‐value: 0.03) followed by VRMEM (B: ‐0.06, 95% CI: ‐0.15, 0.03, p‐value: 0.18) and SEM (B: 0.00, 95% CI: ‐0.08, 0.08, p‐value: 0.97). Effect modification was suggested for VRMEM (WMH x education B: ‐0.03, 95% CI: ‐0.06, 0.00, p‐value: 0.09) but not EF (WMH x education B: ‐0.01, 95% CI: ‐0.04, 0.03, p‐value: 0.74) or SEM (WMH x education B: 0.00, 95% CI: ‐0.04, 0.03, p‐value: 0.79).

Conclusion

The relationship between WMH and late‐life cognition differed by cognitive domain with the strongest effect of WMH independent of education for executive functioning, and effect modification by education for the relationship between WMH verbal episodic memory.
Association of frailty with cognitive impairment in Mexican older adults from the open population
Authors: Ruiz‐Castillo Karla Paulina
Published: December 2021

Background

Frailty and mild cognitive impairment are highly prevalent and disabling conditions in the older adult population, which can coexist. Since fragility represents wear and tear of multiple systems that put the subject in a condition of physical, cognitive, and social vulnerability,

Method

This report contains information from an observational cohort design study, the inclusion criteria included adults older than 65 years or older at the beginning of follow‐up, who completed the baseline evaluations and three years of follow‐up, within the protocols of the GID 10 / 66. Data from 1,823 adults older than 65 years without dementia were analyzed in the initial evaluation. Frailty was evaluated by modified Fried criteria (excluding grip strength), the presence of 3 of the 4 remaining criteria was considered fragility. They were considered for the analysis of variables such as sex, age, education, marital status, occupation, diabetes, hypertension, depression, anxiety, and cognitive impairment level in the initial evaluation. The incidence of cognitive impairment was determined by the presence of MCI or dementia at the follow‐up evaluation.

Result

The prevalence of frailty in the baseline evaluation was reported in 6.1%. Frailty was more prevalent in older ages. The occupation was also found to be associated with frailty, more prevalent in unemployed older adults. Comorbidities such as diabetes, a history of cerebral vascular disease, depression, and anxiety were found to be associated with frailty. The incidence of cognitive impairment in the total sample was 14.6%, in the group with frailty in the baseline evaluation it was 30.0%, which translates into a risk ratio of 2.2, which is reduced to 1.8 when adjusted for risk variables for incident cognitive impairment such as age, schooling, diabetes, depression, and anxiety.

Conclusion

In older adults from the open population, frailty is associated with the incidence of cognitive impairment independently of some of the known risk factors for dementia and mild cognitive impairment.
Extracellular vesicle miRNA from cerebrospinal fluid as potential biomarkers for neurodegeneration
Authors: McFarland Trevor J. , Sandau Ursula S. , Smith Sierra J. , Baker Sarah Catherine , Saugstad Julie A.
Published: December 2021

Background

Extracellular vesicles (EVs) are a diverse group of small membranous particles classified by protein and nucleic acid content, size, method of biogenesis, and cellular origin. The need for predictive biomarkers for neurodegenerative disease is critical for early detection and potential therapeutic intervention. We have previously identified multiple high ranking miRNAs in total cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD). To investigate whether these miRNAs are released from cells within EVs, we developed a pipeline to isolate and analyze EV miRNA.

Method

EVs are isolated by size exclusion chromatography (SEC) from CSF collected from living donors. EV counts and sizes are determined by nanoparticle tracking analysis (NTA). Immunoblots are used to characterize EV composition and assess purity. Transmission electron microscopy (TEM) is used to assess size and EV structural characteristics. EV total RNA is isolated using commercial based methods. Quantitative PCR (qPCR) is performed using TaqMan Low Density Array (TLDA) miRNA cards.

Result

The CSF EV isolation protocol developed here is capable of isolating pure vesicles of the appropriate size and protein composition. Following miRNA qPCR, more than half of the high ranking miRNAs identified in total CSF from AD patients were observed in the isolated EV population.

Conclusion

This pipeline is suitable for isolating EVs and assessing miRNA content in lumbar CSF. A large number of miRNAs isolated from EVs appear to correlate well with previously published data from total CSF, indicating a potential role for EV miRNA cargo as biomarkers for neurodegenerative diseases such as AD.
Effect of COVID‐19 in cognitive manifestations in people with dementia of Alzheimer’s type
Authors: Rai Pooja , Singh Indramani L. , Singh Tara , Tiwari Trayambak , Joshi Deepika
Published: December 2021

Background

The coronavirus disease 2019 (COVID‐19) has been spreading worldwide and affecting people of all the age groups. Recent studies are claiming that it causes brain fog state in patients. The elderly are more prevalent in this disorder because of higher medical comorbidities and resulting in cognitive impairments.

Method

The present study has taken 2 cases of dementia of Alzheimer’s disease patients with Covid 19 positive as experimental and 2 cases of Alzheimer’s disease patients with Covid 19 negative as control group. A video interview has been structured with few questions to assess their cognitive perspective on Covid 19. They have been matched on cognitive status using Hindi‐ mini Mental State Examination and Cognitive Failure questionnaire. After a period of two month they have been interviewed again to compare the changes.

Result

The findings of the present study revealed a differences in the scores of Cognitive Failure Questionnaire in experimental group as compared to control group.

Conclusion

The study showed that there was an effect of Covid 19 on cognitive status of cases of dementia of Alzheimer’s disease patients with Covid 19 positive as compared to dementia of Alzheimer’s disease patients with Covid 19 negative cases.
Lessons from COVID‐19 pandemic: Clinical experiences on telemedicine in patients with dementia in Iran
Authors: Noroozian Maryam , Mohammadian Fatemeh
Published: December 2021

Background

One of the impacts of COVID‐19 pandemic on health system has been increasing the burden on the patients with dementia and their families. Telemedicine has shown to be a solution for this vulnerable group and can be used for cognitive assessment, medication adjustment, patient referral, reduces the travel time, cost and caregiver burden. Despite the challenges in acceptance for this novel technology in the elderly 1, it can reduce the burden of disease and increase access to specialised services. All these alongside neurologic visit could be provided with a telephone hotline or preferably video‐platform tele‐visit.2 However, barriers to develop telemedicine include a lack of broadband internet access and the need for insurance coverage.3 The American Academy of Neurology has been developed a comprehensive guideline to implement the tele‐visit approach in the COVID‐19 crisis with a special approach to neurological examination limitations in the patients.4 Numerous studies evaluated this approach to assess patients including dementia.5 Overall, the patients, caregivers, and the neurologists reported a high satisfaction rate.6 Yaadmaan Institution for Brain, Cognition and Memory Studies with a multidisciplinary team including cognitive neurologist, psychiatrist, psychologist, geriatrician, and clinical pharmacist is the first private referral center for cognitive disorders in Iran. After starting quarantine and tight restrictions and because of too many families who were seeking help for their patients via Yaadmaan helpline, we decided to start Telemedicine method. The approach and compatible examinations have been shown in Table 2 and 3 respectively. In addition, we defined a list of serious states to avoid Telemedicine for patients referal to the hospital in Table 4. Based on our one‐year experiences, it seems there are promising results in‐terms of feasibility, acceptability and convenience for the patient, caregiver and physician. However, due to the emergence of this pandemic, Telemedicine and its crucial role in Iran has not yet been identified in the insurance and health system appropriately. Even though Telemedicine was started as a practical and urgent solution against COVID‐19 restrictions, it is necessary to be evaluated as an alternative method for clinical evaluations of the patients with dementia in Iran in the future.
Institutional experience on cognitive screening at the Medicare Annual Wellness Visit
Authors: Lee Patricia R , Godfrey Wesley B , Raza Arwa , Xi Romi , Brea Carolina , Smith Zhana , Schnell Patrick M , Li Guibin
Published: December 2021

Background

Screening for cognitive impairment is required at Medicare Annual Wellness Visits (AWV). Subjective or objective methods are suggested, but there is no one screening tool specified by Centers for Medicare and Medicaid Services (CMS). We assessed screening methods, its outcomes, and potential disparities in cognitive screening at AWV.

Method

Retrospective chart reviews were done for 1,493 adults 55+ who had initial AWV at a single academic medical center ambulatory site between January 2011 and March 2017. Demographics, assessment type, and positive screens noted by provider were collected. Subjective assessments were by history/direct observation alone. Objective assessments are noted in Table 1. Multiple logistic regression with stepwise variable selection via AIC were done.

Results

Mean age was 73.6 years (SD=7.9); 828 (55.5%) were female; 1191 (79.8%) were white (Table 2). 1,311 were screened for cognitive impairment, 120 were not screened, and 62 had an established diagnosis. Of those screened, 87.5% were screened using objective methods; greater age (p<0.001), African American race as compared to white race (p<0.001), and non‐English primary language (p=0.03) were associated with increased probability of positive screens. In subjective screening (n=163), speaking a non‐English primary language was associated with higher probability of positive screening (p = 0.04). In patients with positive screens through any method, 41 had no further cognitive assessment planned, 19 had plans for follow‐up, 15 were referred to neurology.

Conclusion

AWV are an opportunity to screen for underdiagnosed cognitive impairment. Clinicians in our study used a myriad of tests, despite each test’s unique limitations. Greater age, African American race, non‐English primary language being associated with increased probability of positive objective screening is consistent with the literature. In subjective screenings, patients with non‐English primary language were more likely to screen positive, suggesting that in AWV, non‐English speaking patients may be at a disadvantage for standard cognitive screening. Despite positive cognitive screening, the majority had no further cognitive assessment planned during the visit. Our study suggests that more research should focus on a standardized cognitive screening and decision making after a positive cognitive screening at AWV.
Associations between apathy and fatigue in patients with neurocognitive disorders
Authors: Daumas Lyne , Manera Valeria , Robert Philippe , Zory Raphael
Published: December 2021

Background

Apathy and fatigue are two disabling symptoms of neurocognitive disorders causing a reduction of activity in daily functioning, including in motor activity, and contributing to loss of autonomy. Fatigability is characterized by a reduction in the ability to produce a motor work during a physical task and is a central element in the circle of deconditioning because many activities of daily living require the ability to exert effort over an extended period of time. This study aims to explore the fatigability of apathetic and non‐apathetic patients with neurocognitive disorders (ND).

Method

20 subjects (out of 40 still to include) with mild to major ND (age= 78,0 ± 6,3y, MMSE= 26,0±2,3) were classified as apathetic (n=10, BMI= 25 ± 2,5) vs non‐apathetic (n=10, BMI= 25 ± 4,5) based on the apathy diagnostic criteria[1]. Subjects performed a 6 minutes walk test, a handgrip test with a sustained maximal isometric contraction for 15 seconds, and a sit to stand task until exhaustion surrounded by a maximal voluntary contraction of extensors knee.

Result

Preliminary results showed a significant greater decrease of performance in apathetic patients during the handgrip sustained maximal isometric test (p=0,028). On the 6 minutes walk test and the sit to stand task, no significant differences of fatigability index were found between two groups.

Conclusion

The greater decrease of performance during the handgrip test suggests a higher fatigability in apathetic ND patients. This is not yet confirmed by the two other tasks, probably due to the small sample size. As data collection for the study will finish in June 2021, I will present at the conference more reliable results. Reference: [1] Robert P, Lanctôt KL, Agüera‐Ortiz L, et al. Is it time to revise the diagnostic criteria for apathy in brain disorders? The 2018 international consensus group. Eur Psychiatry. 2018;54:71‐76.
Associations between the use of histamine‐2 receptor antagonists vs. proton pump inhibitors and cognitive decline: A stratified longitudinal study in people with and without cognitive impairment
Authors: Wu Che‐Yuan , Xiong Lisa Y , Ouk Michael , Edwards Jodi D , Rabin Jennifer S , Herrmann Nathan , Lanctôt Krista L , Kapral Moira K , Law Marcus , Swardfager Walter
Published: December 2021

Background

Studies suggest associations between proton pump inhibitors (PPI) and higher dementia risk compared with no use; however, several studies did not consider histamine‐2 receptor antagonists (H2RAs), the other common acid suppressant for similar indications. Comparisons between them are clinically relevant, both in older people with and without cognitive impairment due to Alzheimer’s disease (AD).

Method

Participants using a PPI or H2RA were selected from the National Alzheimer's Coordinating Center database from September 2005 to February 2021. Cox regressions were used to compare 5‐year conversion from normal cognition to mild cognitive impairment (MCI) or dementia, and 5‐year conversion from MCI to dementia, between PPI and H2RA users. In a propensity score matched sample of clinically diagnosed mild‐moderate AD, a linear mixed‐effects regression was used to assess PPI vs. H2RA use in rates of decline in global cognition (Clinical Dementia Rating [CDR®] Sum of Boxes; CDR‐SOB) up to 5 years. Delayed memory recall (Wechsler Memory Scale–Logical Memory test) was explored using a mixed‐effects negative binomial regression. Demographics, smoking, alcohol abuse, baseline CDR‐SOB, comorbidities, concurrent medications used, and apolipoprotein E genotype were included as covariates in Cox regressions or in propensity score.

Result

Cognitively normal H2RA (n=547, events=62) vs. PPI users (n=2237, events=312) did not differ in their risk for MCI or AD (Hazard Ratio; HR [95% Confidence Interval; CI] = 1.067 [0.807‐1.410]). In MCI, H2RA use (n=288, events=75) was associated with faster 5‐year dementia conversion (HR [95% CI] = 1.402 [1.085‐1.811]), compared with PPI use (n=1413, events=355). In AD, H2RA (n=212) vs. PPI (n=636) use was not associated with differential rates of decline in global cognition (B [95% CI] = ‐0.023 [‐0.324, 0.277] CDR‐SOB per year). However, H2RA use was associated with faster memory decline (Rate Ratio [95% CI] = 0.783 [0.671‐0.915]) in AD, but no associations with memory decline were found in MCI or normal cognition.

Conclusion

Differential associations with cognitive decline were not observed in cognitively normal older people. Among people with MCI or AD, H2RA use was associated with faster rates of conversion to dementia, or memory decline, respectively. Anti‐cholinergic burden might explain the associations.
ICARE AD‐US: Design of a prospective, single‐arm, multicenter, noninterventional real‐world study of aducanumab in the United States
Authors: Galvin James E. , Cummings Jeffrey L. , Benea Mihaela Levitchi , de Moor Carl , Atri Alireza , Porter Verna R. , McEwen Sarah C. , Rubino Ivana
Published: December 2021

Background

Aducanumab is a human monoclonal antibody that selectively targets aggregated forms of amyloid beta (Aβ), including soluble oligomers and insoluble fibrils, and, at the writing of this abstract, is currently under review by the US Food and Drug Administration (FDA), European Medicines Agency, and Pharmaceuticals and Medical Devices Agency (Japan). The efficacy and safety of aducanumab have been evaluated in 2 identically designed, randomized, placebo‐controlled, double‐blind Phase 3 studies in early Alzheimer’s disease (AD); however, should aducanumab be approved, it will be critical to effectively evaluate its long‐term impact in the real world.

Method

ICARE AD‐US is a prospective, single‐arm, multicenter, noninterventional study of aducanumab, as prescribed in a postmarketing, real‐world US setting. This Phase 4 observational study is designed to evaluate the safety and effectiveness of aducanumab in real‐world clinical practice per its FDA‐approved labeling in the US. The primary objective of the ICARE AD‐US study is to evaluate progression of AD in aducanumab‐treated patients as determined by a predefined, uniform set of cognitive, functional, and neuropsychiatric and global severity measures and to characterize the longitudinal impact of aducanumab on quality of life, disease burden, and health care resource utilization. ICARE AD‐US will also assess the long‐term safety of aducanumab as measured by the incidence of serious adverse events and the incidence of amyloid‐related imaging abnormalities‐edema (ARIA‐E). Biobanking of collected blood (plasma and serum) will provide the opportunity for future biomarker studies.

Result

ICARE AD‐US aims to enroll approximately 6000 patients with AD over 4 years, including approximately 500 African American and 500 Hispanic/Latinx patients, from approximately 200 sites in the US. Patients will be monitored in a real‐world setting for a period of up to 5 years.

Conclusion

The evidence generated in the ICARE AD‐US study will not only enable the collection of consistent long‐term efficacy and safety data to assess the impact of aducanumab treatment in the real world but will also support the measurement and characterization of AD progression and the optimization of clinical practice through standardization of the diagnosis of early AD and identification of individuals who may benefit from treatment.