bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical reinstatement in the visual associative memory network is compromised by early tau in normal older adults
Authors: Mormino Elizabeth C. , Trelle Alexandra N. , Hunt Madison , Tran Tammy , Carr Valerie A. , Toueg Tyler , Deutsch Gayle , Harrison Marc , Sha Sharon , Rutt Brian S. , Kerchner Geoffrey A. , Wagner Anthony D.
Published: February 2022

Background

The structure and computations associated with specific hippocampal subfields decline in aging and are also initial sites of Alzheimer’s disease pathology. The degree to which age‐associated changes in hippocampal‐dependent memory are driven by early AD pathology among older normal adults remains unclear.

Method

We enrolled one hundred ninety‐nine clinically unimpaired (CU) older individuals into the Stanford Aging and Memory Study (SAMS, 117 Female, mean age= 68.9±6.2). Participants completed a lumbar puncture to collect cerebrospinal fluid (CSF), high‐resolution fMRI (at 3T) during a visual associative memory paradigm, and ultra high‐resolution structural MRI (at 7T) to assess MTL subregion integrity, as well as extensive cognitive assessment. Data collection is complete, and analysis of fMRI and 7T structural data of the 199 participants is currently underway. To examine neuronal computations underlying hippocampal dependent memory, we focused on fMRI metrics in a subset of 78 participants that quantify cortical reinstatement (the degree to which voxelwise patterns of activation during retrieval match activation patterns during encoding) in two a priori regions known to be important for visual associative memory (ventral temporal cortex, VTC; and angular gyrus, ANG). Additionally, we extracted univariate fMRI signal from the hippocampus during successful retrieval. Finally, hippocampal thickness from CA1 in a subset of 77 participants was manually delineated on 7T scans, and CSF was processed with Lumipulse to measure Ab42:Ab40 ratio and p‐tau181.

Result

Elevated p‐tau181 was associated with worse performance on the fMRI‐scanned visual associative memory task (Figure A), reduced cortical reinstatement strength in both VTC (r = ‐0.25, p = .027, Figure B) and ANG (r = ‐0.22, p = .048), as well as reduced CA1‐SRLM thickness (r = ‐0.32, p = .004, Figure C). Although Ab42:Ab40 ratios were related to p‐tau181, they were not independently associated with neuronal indices of hippocampal‐dependent memory.

Conclusion

CU with evidence of early tau abnormalities show worse hippocampal‐dependent memory and differences in fMRI and structural measurements in regions critical for successful associative memory. Initial consequences of AD pathology target specific hippocampal‐cortical circuits, and this is measurable using advanced MRI techniques.
APOE ε4 predicts amyloid PET positive in amnesic subjective cognitive decline
Authors: Yang Dong Won , Hong Yun Jeong , Ho SeongHee , Jeong Jee Hyang , Park Kee Hyung , Kim Sangyun , Wang Minjung , Choi Seong Hye , Han SeungHyun , Kang Seung Wan
Published: February 2022

Background

Subjective cognitive decline (SCD) has been considered as at risk state to progress to mild cognitive impairment(MCI) or Alzheimer's disease(AD). Apolipoprotein E e4 allele is a well‐known genetic risk for rapid deterioration of cognitive and dementia development. We investigated the effect of APOE ε4 on the brain amyloid pathology and other clinical features in the elderly with SCD.

Method

One hundred and nineteen elderly subjects, 60 or older, complaining of persistent cognitive decline, with 7% to 50% of the memory test score and over 7% of the other tests score were included through neuropsychological tests(Seoul neuropsychological battery, SNSB). Brain magnetic resonance imaging (MRI) volumetry, visual and standardized uptake value ratio (SUVR) analysis of 18F‐Florbetaben brain amyloid‐beta Positron Emission Tomography (PET) were performed. Demographics, physical data, social and physiological functions were also obtained.

Result

Of the 119 SCD subjects, 26 (21.8%) had APOE ε4 and 26 (21.8%) had amyloid PET positive. Age was not different between two groups (70.9 V.S. 70.9, p=0.880). Test Z‐score was only marginally lower in Digit span test‐forward (p=0.053) in SCD with APOE ε4. Amyloid PET SUVR value was higher in SCD with APOE ε4 (1.2±0.2 V.S. 1.5±0.3, p=0.001). Regional brain volume including hippocampus and entorhinal cortex were not different in SPM based volumetric ananlysis. Korean_Everyday Cognition subscores, depression scores measured with Patient Health Questionnaire 9, sleep quality measured with Pittsburgh Sleep Quality Index total score, Body Mass Index, and gait speed were not different between two groups.

Conclusion

With the baseline data, APOE ε4 was associated with decreased attention and higher brain amyloid accumulation in amnestic SCD. Longitudinal data will be needed to clarify whether APOE ε4 is associated with progression of cognitive dysfunction in SCD. This study was supported by a grant from the Ministry of Health and Welfare, HI18C0530.
The persistence and longitudinal impacts of sleep disturbances in nursing home residents with dementia
Authors: Webster Lucy A , Gonzalez Sergi Costafreda , Barber Julie , Livingston Gill
Published: February 2022

Background

Sleep disturbances are common in people living with dementia, with a prevalence of 40%. These disturbances may be the reason people with dementia move into a nursing or residential care home. However, there is little research into the persistence and long‐term impacts of sleep disturbances in this population, and this has practical implications on if and how these disturbances should be treated, and we aimed to investigate this.

Method

We used data from the MARQUE (Managing Agitation and Raising QUality of lifE) cohort study, with data collected from 1483 care home residents with dementia every four months for 16 months; the largest care home study in England, UK. Outcomes collected at every time point included quality of life, hospital admissions, mortality, medication, and sleep disturbances; which were defined as either any symptoms or clinically significant cases when the symptoms were more frequent and severe (defined as score ≥4 on the Neuropsychiatric Inventory sleep item).

Result

Most participants were female (69%), with a median age 86 years. Nearly a third of residents (31%) had a clinically significant case and nearly half (47%) of residents had symptoms of sleep disturbance across the study. Of those with clinically significant cases at baseline, 16% remained persistent cases, 46% fluctuated, and 38% did not have a clinically significant case again. Furthermore, residents with clinically significant cases longitudinally had a lower quality of life (regression coefficient ‐3.94, 95% confident intervals (CI) ‐4.82–‐3.06), and were significantly more likely to be prescribed sleep medications (odds ratio (OR) 1.57, CI 1.02–2.42). Residents who had a clinically significant case at baseline were more likely to have a hospital admission at follow‐up (OR 1.52, CI 1.07–2.14), but were not more likely to die during follow‐up (hazards ratio 0.93, CI 0.71–1.22).

Conclusion

As sleep disturbances fluctuate or persist in most residents who have them, this highlights the importance of treatment for these disturbances, as they mostly will not resolve without it. As these disturbances also negatively impact people with dementia’s quality of life and increase the likelihood of hospital admissions, they are therefore a priority for treatment.
At‐homeness: A novel psycho‐socio‐environmental construct for an eMental Health controlled trial to prevent loneliness and cognitive decline among older adults with multimorbidity
Authors: Gan Daniel RY , Chaudhury Habib , Best John R , Rowles Graham , Wister Andrew
Published: February 2022

Background

Approximately two‐thirds of older adults’ experience multimorbidity in Canada and the US. Challenges of symptoms management and reduced mobility often coincide with late‐life depression which is associated with a 2 to 5‐fold increased dementia risk. Loneliness and depression are connected in the prodromal phases. Loneliness is distinct from social isolation and has direct neurological impact on the brain (Cacioppo et al., 2014). Yet, recent umbrella review of RCTs on loneliness reported “limited effects” (Jarvis et al., 2020). Following recommendations for theory‐based non‐pharmacological interventions (Sikkes et al., 2020), this paper develops a novel construct as an antidote to loneliness for eMental Health intervention among MMOA.

Method

Findings from three sequential studies were combined to examine the preventive potential of a measurable construct. (1) Systematic review identified 28 studies on the experiences people living with dementia in the community. Comparative synthesis was conducted ethnographic data (e.g., in‐depth interviews) since Chaudhury (2001). (2) Primary qualitative data were extracted to generate items for a preliminary scale. Factor analysis was conducted to examine construct validity. (3) An index was constructed using comprehensive data from the Canadian Longitudinal Study on Aging (CLSA). Path analysis was conducted to examine direct and indirect effects on loneliness, depression, and cognition, controlling for baseline. Social environment (e.g., social support) was included for comparison.

Result

(1) Understanding behavioral symptoms as non‐verbal expressions and employing Deweyan person‐place integration, at‐homeness emerged as a psychological construct that could address prodromal loneliness. (2) Factor analysis (n=212) reduced 28 items to 20 items (α=.920) At‐homeness includes three factors: identity‐stability(α=.886), social experiences (α=.887), self‐expression (α=.767)(SRMR=.075). Convergent validity with neighborhood factors was found (B=.43, p<.001). (3) Measures of housing, neighborhood, and life satisfaction were used. Path analysis (n=15,087) showed good model fit indexes (TLI=.989; CFI=.999; RMSEA=.026; SRMR=.006). At‐homeness (B=‐.20, p<.001) rivals the effect of social environment (B=‐.19, p<.001) on loneliness. Structural equation modelling showed that, together, at‐homeness and loneliness have as much effect on cognition as depression.

Conclusion

At‐homeness is a promising novel psycho‐socio‐environmental construct to reduce loneliness and cognitive decline among MMOA. Its factors may be influenced through customized activity suggestions. A pilot study is underway.
Multimodal assessment of locus coeruleus integrity is associated with late‐life memory performance
Authors: Dahl Martin J , Bachman Shelby L , Dutt Shubir , Düzel Sandra , Lindenberger Ulman , Kühn Simone , Werkle‐Bergner Markus , Mather Mara
Published: February 2022

Background

Abnormally phosphorylated tau, an indicator of Alzheimer’s disease, accumulates in the first decades of life in the locus coeruleus, the brain’s main norepinephrine supply. Recent advances in brainstem magnetic resonance imaging (MRI) suggest an association between in‐vivo locus coeruleus integrity and Alzheimer’s‐related neuropathology. However, while MR sequences have demonstrated their sensitivity for the locus coeruleus, a complete understanding of the underlying contrast mechanisms is still lacking.

Method

To investigate whether common locus coeruleus imaging approaches measure the same construct, younger and older participants of the Berlin Aging Study‐II (n ∼ 320) underwent 3T‐MRI. The imaging protocol included three scans sensitive for the locus coeruleus—a Fast‐Spin‐Echo [FSE] sequence focused on the brainstem, and a Magnetization‐Transfer sequence, acquired once with a dedicated magnetic saturation pulse [MT] and once without, resulting in a proton‐density like image [noMT]. Participants moreover completed a comprehensive cognitive battery, including tests of fluid intelligence, episodic and working memory, to assess whether different imaging protocols relate to similar aspects of late‐life cognition.

Locus coeruleus MR‐intensity ratios, a non‐invasive proxy for neuronal density, were semi‐automatically extracted from FSE, MT, and noMT scans in standard space. We integrated locus coeruleus ratios across imaging modalities to derive a latent, multimodal factor expressing locus coeruleus integrity. Similarly, we used a previously established cognitive factor structure to integrate performance across multiple cognitive tasks to retrieve latent measures of fluid intelligence, episodic and working memory.

Result

Locus coeruleus‐related hyperintensities were reliably detected across imaging modalities (see Figure 1). Crucially, locus coeruleus ratios derived from different imaging modalities were strongly interrelated in younger and older adults (see Figure 2), indicating a common construct. However, age‐group differences in locus coeruleus ratios were modality‐specific, warranting caution in cross‐study comparisons. Merging neural and cognitive models, we found that higher locus coeruleus ratios were related to better episodic memory performance in later life. This association was observed for multimodal locus coeruleus integrity and was replicated for each imaging modality (see Figure 3).

Conclusion

Our findings support the utility of brainstem MRI as proxy for locus coeruleus integrity and highlight a role of the noradrenergic system in late‐life memory decline.
The Brain Health Champion (BHC) Study, COVID‐19 sub‐study: The impact of COVID‐19 on behaviors adopted following interventions to promote brain‐healthy activities
Authors: McFeeley Brittany , Krivanek Taylor , Nicastri Casey M , Daffner Kirk R , Gale Seth A
Published: February 2022

Background

Evidence suggests that brain‐healthy behaviors, such as exercise, a Mediterranean diet, and cognitive/social stimulation, help protect against the risk of cognitive decline and dementia. We have been studying two interventions (health coach vs. physician education) that promote brain‐healthy behaviors in patients with mild dementia (MD), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and those at‐risk. When COVID‐19 occurred, we became interested in determining the extent to which the pandemic may have interfered with brain‐healthy behaviors that participants had adopted. We designed a sub‐study to investigate the pandemic’s effects on adherence to brain‐healthy behaviors in participants who completed either intervention in one of our two Brain Health Champion studies (BHC‐1, BHC‐2).

Method

Participants from BHC‐1 and BHC‐2 were emailed questionnaires in September 2020. Of the 25 respondents, 15 (SCD:2, MCI:8, MD:5) were from BHC‐1 and 10 (At‐risk:5, MCI:5) were from BHC‐2. Questionnaires measured changes from the start of the pandemic (March 2020) in self‐reported physical activity, diet, and social/cognitive activities, as well as current sleep quality and feelings of anxiety and depression.

Result

Results demonstrated that the pandemic had negatively impacted physical activity (p=.009) and social interactions (p<.001), with no significant changes in diet or cognitive activities. Additional data trends show that at‐risk/SCD participants endorsed more feelings of anxiety and depression than MCI participants. At‐risk/SCD participants also reported worse sleep quality than MCI participants (p=.036) across both studies and intervention arms.

Conclusion

Our findings suggest that the pandemic significantly impacted activities typically done outside the home (social and physical activity), while activities that are typically done at home were less affected (Mediterranean diet adherence and cognitive activity). The pandemic seemed to diminish brain‐healthy behaviors that participants likely gained from the interventions, demonstrating that clinical/research programs aimed at promoting brain health are strongly influenced by changes in the environment. Trends also show that there may be a direct relationship between anxiety/depression symptoms and sleep disruption in at‐risk/SCD and MCI participants. More research is necessary to determine if these disruptions of behavior and sleep are temporary and will be well‐compensated when COVID‐19 restrictions are lifted.
Hypertension and race affect cerebral blood flow and cognition in older adults without dementia
Authors: Swinford Cecily G. , Risacher Shannon L. , West John D. , McDonald Brenna C. , Unverzagt Fred W. , Gao Sujuan , Farlow Martin R. , Apostolova Liana G. , Wu Yu‐Chien , Brosch Jared R. , Deardorff Rachael , Wang Sophia , Kamer Aaron P. , Wang Danny J.J. , Saykin Andrew J.
Published: February 2022

Background

It is known that African Americans have a higher prevalence of AD than white Americans, but it is not fully understood why this is the case. One potential explanation is that African Americans also have a higher prevalence of cardiovascular risk factors, which also confer a risk for AD. Racial differences in several AD‐specific and cardiovascular disease biomarkers have been reported, but these findings are generally not conclusive. In addition, very few papers have assessed racial differences in cerebral blood flow (CBF), an important noninvasive biomarker for AD/dementia. We investigated the relationships between cerebral blood flow (CBF), race and hypertension in a cohort of older individuals without dementia.

Method

Participants included 116 older individuals, 21 (18%) African American, who were cognitively normal (CN), had subjective cognitive decline (SCD), or had mild cognitive impairment (MCI). 3D pseudo‐continuous arterial spin label (pCASL) MRI on a Prisma 3T and cardiovascular risk factors and cognitive domain z‐scores from the time of scan were analyzed. Multiple regression was used to assess the relationships between race, hypertension, and CBF on a region‐of‐interest and voxel‐wise basis with age, sex, diagnostic group and total grey matter volume as covariates.

Result

Region‐of‐interest and voxel‐wise CBF was decreased in African Americans and in individuals with hypertension. While there was overlap between the affected regions, especially temporal lobes, hypertensive individuals also had decreased CBF in anterior brain regions, while African Americans had decreased CBF in posterior brain regions. The effect of race on CBF remained after hypertension was included as a covariate. Despite the regional overlap, there was no interaction of race and hypertension on CBF. Perfusion in affected brain regions was positively correlated with attention in all participants, as well as with visuospatial function in African Americans.

Conclusion

Hypertensive individuals and African Americans have decreased CBF in partially overlapping brain regions. Decreased CBF in these regions was differentially associated with cognitive function according to race. Further study of CBF in larger diverse samples is warranted.
Informant measures of cognition in the Mexican Health and Aging Cognition Study
Authors: Cantu Phillip A , Wong Rebeca , Arango Silvia Mejia
Published: February 2022

Background

To describe the correlates of informant assessed cognitive functioning among older Mexican adults.

Method

We include participants in the 2016 Mexican Health and Aging Study Cognition Study Informant Questionnaire (MexCog). Cognitive functioning, measured by total Community Screening Instrument for Dementia (CSID), and CSID split into a cognition and functioning component are regressed as a function of participant characteristics, informant characteristics, and relationship characteristics.

Results

Informant measurements of cognition have distinct correlates from direct measurements. Participant education is significantly associated the total CSID and the cognition component but not the functioning component. Community size is not significantly associated with informant measures of cognition. Spousal informants reported higher total CSID scores and cognitive component but were not significantly associated with the functioning component. Other family members and other non‐family members reported fewer CSID cognition items than spouses.

Conclusion

Spousal informants may be more attuned to their partners cognitive functioning than other informants. Functional components and cognitive components of the CSID measure distinct domains and have different correlates.
Correspondence between cortical tau and atrophy in aged non‐demented adults with Down syndrome
Authors: Taylor Lisa , Doran Eric , Poline Jean‐Baptiste , Nguyen Dana , Krinsky‐McHale Sharon J. , Price Julie C. , Sathishkumar Mithra , Kreisl William Charles , Hom Christy , Pulsifer Margaret , Lai Florence , Rosas H. Diana , Brickman Adam M. , Schupf Nicole , Silverman Wayne , Lott Ira T. , Yassa Michael A. , Keator David
Published: February 2022

Background

Individuals with Down syndrome (DS) have a higher likelihood of developing early‐onset Alzheimer’s disease which has been associated with abnormal tau proteins and atrophy in the brain [1]. Prior research has shown a spatial relationship between tau and atrophy in neurotypicals with dementia [2]. Although tau and atrophy certainly contribute independently to dementia, the synergistic relationship in a non‐demented population with DS is not well understood. This study aims to identify cortical regions with high tau and atrophy in aged, non‐demented participants with DS.

Method

Analysis included 28 non‐demented participants (49.8 +/‐ 6.4 years; 17 males) with DS from the Alzheimer’s Disease in Down Syndrome (ADDS) study. Tau PET (18F‐AV1451) and MRI scans were acquired within the same timeframe (1.8 months +/‐1.5). Gray‐matter cortical ribbons were extracted from T1 MRI segmentations with Freesurfer (RRID: SCR_001847). The cortical ribbons were used to mask the coregistered PET scan data and converted to standard uptake value ratio (SUVR) units using the cerebellar cortex reference region. The tau and gray‐matter images were converted to z‐score images using the group mean and standard deviation. We defined high tau as voxels with z‐scores >=2.0 and high atrophy as voxels with gray matter z‐scores <= ‐2.0. The z‐score images were spatially normalized into MNI space with ANTs (RRID: SCR_004757) and a voxel‐based correspondence analysis was performed. Voxels surviving the high tau and high atrophy thresholds were evaluated to determine anatomical localization using the Desikan/Killiany atlas [3].

Result

We found high correspondence between tau and atrophy in the following regions (figure 1): entorhinal cortex, insula, fusiform, pars orbitalis, paracentral, precentral, superior temporal, medial orbitofrontal, lateral orbitofrontal, temporal pole, rostral middle frontal, superior frontal, pars triangularis, lingual, and the amygdala.

Conclusion

Our study demonstrated a correspondence between atrophy and tau in deep cortical structures, as well as frontotemporal regions in aged, non‐demented adults with DS. Many of these regions are consistent with findings in neurotypical populations and shown in our prior work to be regions associated with increased amyloid (18F‐AV‐45) as a function of disease severity in DS [4].
Usability and functional validation of artificial intelligence‐enabled technology services in dementia care using a controlled trial in clinical practice
Authors: Savoia Sarah E , Stern Edith H , Salardini Arash , Dorai Chitra
Published: February 2022

Background

Many community settings lack emotional, social, and educational resources to support persons living with dementia (PLWD) and their families, which contribute to the stressors associated with caregiving, termed "caregiver load." This paper describes the impact of artificial intelligence (AI)‐enabled personalized assistive and decision support services on improving dementia care management and reducing caregiver load. We present a study that assesses AI’s usability and functionality in the outpatient setting and is built off of two prior pilots, with each pilot expanding in its scope of technology provided, target population, and caregiving needs.

Objectives

: The study’s primary outcome is the functionality and usability of AI services, collectively called NeuViCare, as measured by the System Usability Scale (SUS) from caregivers. Secondary outcomes include: 1) reduction in caregiver load as measured by Oberst Caregiving Burden Scale (OCBS); and 2) increase of caregivers’ knowledge as measured by Dementia knowledge assessment scale (DKAS).

Methods

This one‐arm, open‐labeled trial is recruiting ten patients with MOCA scores of less than 26 and impaired activities of daily living and their one designated caregiver. Caregivers must have a smartphone, tablet, or laptop to access NeuViCare and to utilize all four of its HIPAA and FHIR compliant services for three months: 1) Task‐Support Service 2) Resource Advisor 3) Community; and 4) Knowledge Advisor. Periodic touchpoints with caregiver participants are in place as a safety measure.

Results

The first pilot’s target population was aides from a national home care agency. The survey‐study reported NeuViCare's user experience to be “very positive” and “easy to use”; the quality of its information to be “clear, concise and with good depth”; and, 3) its value to be “useful for less experienced caregivers”. The second pilot focused on family caregivers from Mumbai. This study showed that Knowledge Advisor provided 97% correct answers. This third pilot study targets informal caregivers, and we hypothesize that mean SUS scores will be significantly associated with reduced OCBS scores.

Conclusion

Effectiveness of AI technology in reducing caregiver load will lead to a scalable, cost‐effective solution that can be made available to caregivers everywhere.
Using the Everyday Cognition Scales (ECog), depression, and vascular risk to predict conversion to cognitive impairment in different ethnoracial groups
Authors: Chan Michelle L , Weakley Alyssa , Harvey Danielle J , Carsey Jane , Farias Sarah
Published: February 2022

Background

Our previous work found that greater subjective cognitive concerns (SCC) at baseline was associated with increased risk of developing mild cognitive impairment (MCI) or dementia in Caucasians and African Americans, but not Hispanics. The present study examined whether medical co‐morbidities or depression may account for some of these differences.

Methods

Participants included 205 Caucasians, 101 African Americans, and 95 Hispanics, all cognitively normal at baseline, who are part of the University of California, Davis Alzheimer’s Disease Center longitudinal cohort. SCC was measured using the self‐reported Everyday Cognition Scales (ECog) Memory domain. Over an average of 4.7 years, 116 developed MCI or dementia. Associations with incident cognitive impairment were assessed using Cox proportional hazards models, adjusting for age and education. Models considered the interaction between race/ethnicity and the ECog score, as well as either depression (Geriatric Depression Scale) or vascular risk (proportion present out of hypercholesterolemia, diabetes, hypertension). Models were then run separately in each racial/ethnic group.

Results

In models that included depression and vascular risk separately, there was a significant interaction (p<0.05) between racial/ethnic group and SCC, consistent with our earlier findings. GDS was not associated with progression for any racial/ethnic group (p>0.1), SCC was associated with progression in African Americans (HR=2.05, 95% CI=1.20, 3.50; p=0.009), but not Caucasians (p=0.08) or Hispanics (p=0.34). In contrast, vascular risk was marginally associated with progression in Hispanics (HR=3.4, 95% CI=0.98, 11.72; p=0.054), but not Caucasians (p=0.8) or African Americans (p=0.4). When accounting for vascular risk, SCC was associated with progression in Caucasians (HR=1.7, 95% CI=1.1, 2.6; p=0.01) and African Americans (HR=2.04, 95% CI=1.27, 3.26; p=0.003), but not Hispanics (p=0.4).

Conclusions

Results suggest there are differences in the degree to which SCCs and vascular risk are associated with developing cognitive impairment across different ethnoracial groups. SCC was generally associated with incident impairment in Caucasians and African Americans, but not Hispanics. Medical co‐morbidities were more associated with incident impairment in Hispanics compared to Caucasians.
Modifiable determinants of physical functioning among LGBT older adults with cognitive impairment
Authors: Kim Hyun‐Jun , Fredriksen‐Goldsen Karen , Jung Hailey
Published: February 2022

Background

Heightened risks of cognitive impairment are a critical health concern for lesbian, gay, bisexual, and transgender (LGBT) older adults. The physical and functional declines associated with cognitive impairment are known to increase risks of injury and decrease independent mobility.

Method

Guided by the Health Equity Promotion Model, this study analyzed longitudinal data (T0 to T2, N=646) to examine risk and protective factors predicting changes in physical functioning over time among LGBT older adults with cognitive impairment.

Result

According to the results of multilevel mixed models, social support, physical, recreational, and wellness activities, and nutrition were associated with improvement in physical functioning over two years while stigma contributed to decline in physical functioning.

Conclusion

LGBT older adults with cognitive impairment face unique challenges due to social stigma and isolation. The findings suggest that enhancing their access to community resources and their participations in physical, social, community, and recreational activities would improve their physical functioning.
Meta‐analysis of the associations of biomarkers of amyloid and tau with cognition in cognitively normal older adults
Authors: Ferreira‐Atuesta Carolina , Piendel Lydia A , Emerson Jacqueline M , Joshi Nandita , Hedden Trey
Published: February 2022

Background

Conflicting evidence exists on the in vivo relationship of amyloid and tau levels to cognition among cognitively normal older adults. We conducted a meta‐analysis of reported relationships of biomarkers of amyloid or tau levels with baseline and change in cognition in cognitively normal older adults.

Method

We performed a literature search that returned studies between 2005 and January 2021 for studies reporting a relationship between amyloid or tau biomarkers measured via PET ligands, CSF, or plasma assays, with episodic memory or global cognition. Effect sizes were obtained for each study and weighted by sample size. For studies examining the same cohort, we selected effect sizes from the largest sample size available for each relationship of interest.

Result

One hundred and seven studies (89% reporting cross sectional measures and 62% reporting longitudinal) representing 26968 adults (82% characterized with amyloid measures and 23% with tau) were included. Amyloid levels showed a significant correlation with baseline and longitudinal global cognition (r=0.05, p<0001; r=0.05, p=0.021, respectively), and with baseline episodic memory (r=0.05, p=0.001). Tau was significantly correlated with baseline and longitudinal global cognition (r=0.08, p=0.004; r=0.08, p=0.01, respectively), and with longitudinal episodic memory (r=0.02, p=0.04), whereas the interaction of amyloid and tau was significantly correlated only with baseline global cognition (r=0.09, p=0.024). The overall estimated correlation between amyloid and tau was r=0.17.

Conclusion

In older adults with normal cognition, there is a very small but significant relationship between baseline global cognition and amyloid, tau, and their interactive effect. Episodic memory had a very small but significant relationship with amyloid at baseline and with tau longitudinally. These findings could help determine power estimations for future clinical trials evaluating cognition in asymptomatic older adults. Effect size and power estimations from this meta‐analysis may be limited by unmeasured variability among studies in the timing of biomarker measurement, differences in cognitive assessments, or other cohort‐specific differences.
Clinical outcomes of increased regional amyloid uptake in patients with subthreshold global amyloid levels
Authors: Kim Jaeho , Choe Yeongsim , Park Yuhyun , Kim Yeshin , Kim Junpyo , Seo Younghoon , Jang Hyemin , Kim Hee Jin , Na Duk L. , Cho Soo‐Jin , Moon Seung Hwan
Published: February 2022

Background

Although the standardized uptake value ratio (SUVR) method is objective and simple, cut‐off optimization using global SUVR values may not reflect focal increased uptake in the cerebrum. The present study investigated clinical and neuroimaging characteristics according to regionally increased β‐amyloid (Aβ) uptake and global Aβ status.

Method

We recruited 973 patients with Alzheimer's disease ‐related cognitive impairment (ADCI). All patients underwent neuropsychological tests and 501 18F‐florbetaben (FBB) amyloid positron emission tomography (PET) and 472 18F‐flutemetamol (FMM) PET. Each PET scan was assessed in 10 regions (frontal, temporal, parietal, posterior cingulate, and striatum) by regional quantitative SUVR‐based cutoff values for each region using an iterative outlier approach.

Result

A total of 64 (6.6%) subjects showed increased regional Aβ uptake with subthreshold global Aβ status [focal (+) and global (‐) Aβ group, F(+)G(‐) group]. The F(+)G(‐) group showed worse performance in memory impairment (P < 0.001) and greater hippocampal atrophy (P = 0.024) but not global cognition and cortical thickness, compared to those in the F(‐)G(‐). Participants with diffuse Aβ involvement in the whole region [diffuse (+) and global (+) Aβ group, D(+)G(+)] showed worse neuropsychological (P = 0.008‐0.042) and neuroimaging features (P <0.015) than those with focal Aβ involvement F(+)G(+).

Conclusion

] Our findings suggest that individuals show distinctive clinical outcomes according to regionally increased Aβ uptake and global Aβ status. Thus, clinicians should pay more attention to regional increased Aβ uptake in addition to global Aβ status.
Amyloid, but not tau, is associated with longitudinal change in white matter hyperintensities in a sample of cognitively normal older adults from the Baltimore Longitudinal Study of Aging
Authors: Shaikh Faysal , Resnick Susan M. , Bilgel Murat
Published: February 2022

Background

White matter hyperintensities (WMH) are associated with a greater risk of developing dementia. Hallmark neuropathologies of Alzheimer’s disease (AD), namely, amyloid plaques and tau tangles, begin to aggregate in the brain prior to signs of cognitive impairment. To better understand the relationship between WMH and AD neuropathology in preclinical AD, we assessed via positron emission tomography (PET) and magnetic resonance imaging (MRI) if amyloid and tau are associated with the rate of change in WMH burden among cognitively normal older adults.

Method

89 cognitively normal participants (mean age at PET=76.7 years, 35 men) of the Baltimore Longitudinal Study on Aging underwent 3T fluid attenuated inversion recovery (FLAIR) MRI to assess global WMH burden, 11C‐Pittsburgh compound B PET to assess global amyloid status, and 18F‐flortaucipir PET to assess entorhinal cortex tau. 85 participants had additional FLAIR scan(s) prior to PET visit (mean follow‐up between first and last FLAIR=6.4 years, standard deviation=2.2 years). We assessed the associations of amyloid and tau with retrospective longitudinal WMH burden (in cm3) at and prior to PET scan via a linear mixed effects model (350 observations total). Global amyloid status, entorhinal cortex tau, and their interactions with time from PET were our explanatory variables; our model was adjusted for age at PET, sex, total white matter volume, APOE‐e4 allele carrier status, and vascular risk.

Result

Higher cross‐sectional endpoint global WMH burden was associated with amyloid positivity (estimate=3.050, standard error [SE]=1.366, p=0.028), but not with entorhinal tau SUVR (estimate=−3.233, SE=4.301, p=0.456). Amyloid positivity was also associated with steeper increases in WMH burden in years preceding PET (estimate=0.277, SE=1.366, p=0.037), whereas entorhinal tau was not (estimate=−0.378, SE=0.408, p=0.354).

Conclusion

Amyloid, but not tau, is associated with greater global WMH volume and greater rates of global WMH volume change in our sample of cognitively normal older adults.
Quantifying perivascular space in Alzheimer's disease by MRI relaxometry
Authors: Zhou Liangdong , Nguyen Thanh D. , Wegiel Jarek , Li Yi
Published: February 2022

Background

The perivascular space (PVS) is a known key route of glymphatic clearance for the drainage of interstitial fluid and solutes such as soluble amyloid beta (Aβ) from the brain. Perivascular space dilation in aging could indicate abnormal protein accretion, such as Aβ accumulation. Recent studies indicate that dilation of PVS is associated with blocked cerebrospinal fluid (CSF) bulk flow, which is considered as free water. We propose to use MR T2 relaxometry‐based water compartment model for the quantification of free water in brain parenchyma and hence to infer the change of PVS.

Method

We filtered the 22 Aβ positive MCI subjects with three echo T2‐star data and amyloid PET from ADNI database. The three‐echo data was fitted to a two‐water compartment model (CSF and intro‐extracellular water), in which the water compartments were distinguished by the T2 relaxometry time. CSF fraction (CSFF) values were then extracted in the brain region masks generated from FreeSurfer. Mean CSFF for each subject was then calculated. The SUVr of cerebral cortex was used to evaluate brain amyloid load. Linear regression model between Aβ deposition and CSFF was built with age and gender controlled.

Result

The results from ADNI data show that CSFF is linearly related to the Aβ deposition in brain. Fig. 1 presents a map of CSFF and the amyloid PET for the same subject. Fig. 2 shows linear relationship (p<0.05) between CSFF and the SUVr in the cerebral cortex area.

Conclusion

The relation between CSFF and amyloid load in brain cortex shows that CSFF could be a potential biomarker for the amyloid clearance. The CSFF map reflects the percentage of free water in total volume at the water molecular level and can sensitively detect subtle PVS change.
Communication during Covid‐19: Impacts of face coverings on people living with dementia
Authors: Jeong Tina Hyerim , Volkmer Anna , Jiang Jessica , Brotherhood Emilie V , Dobson Lucianne , Harding Emma , Suarez‐Gonzalez Aida , Crutch Sebastian J , Warren Jason D , Hardy Chris JD , Agustus Jennifer L
Published: February 2022

Background

The compulsory introduction of wearing face coverings and social distancing to curb the spread of Covid‐19 in the United Kingdom has reduced both the quality of auditory information and availability of visual and non‐verbal cues during conversations with others. This is likely to have a greater impact on efficiency and effectiveness of communication for people living with dementia and particularly those with a language‐led dementia: Primary Progressive Aphasia (PPA).

Method

Twenty‐four people living with dementia (PLWD), 95 caregivers (on behalf of PLWD) and 38 healthy older controls anonymously reported their experiences of wearing face coverings and the associated impacts on communication via an online survey that ran between December 2020 and April 2021 (age ranges: PLWD 38‐90 years; controls 32‐100 years). The majority of questions were self‐reflective experiences compared to when not wearing face coverings. Mann‐Whitney U tests were used to compare Likert ratings for impact of wearing face coverings on aspects of speaking, listening and holding conversations between PLWD or diagnosis subgroups (27 PPA; 26 Frontotemporal Dementia, FTD; 29 Alzheimer’s disease, AD; 24 Posterior Cortical Atrophy, PCA) and the controls.

Result

Wearing a face covering made both speaking (80%) and listening (90%) more effortful for the majority of survey respondents and had a greater impact on people living with PPA. Overall PLWD were more likely to require help communicating and those with PPA relied more on non‐verbal strategies (e.g. body language or gestures) than when not wearing a face covering, compared to controls (p=0.001) and other diagnosis subgroups. People with PPA also experienced greater difficulty understanding across diverse everyday listening conditions and most aspects of conversation than controls (p<0.05). People with PCA (p=0.039) also had more difficulty knowing when it was their turn to speak and those with FTD had more difficulty speaking over others (p=0.032), compared to controls. The use of face coverings during the Covid‐19 pandemic also prevented more PLWD from taking part in activities than controls.

Conclusion

PLWD, and in particular those with a diagnosis of PPA, are particularly susceptible to the negative impacts of the use of face coverings on communication.
Impact of COVID pandemic on neuropsychiatric symptoms and caregiver distress in cognitively impaired older adults
Authors: Padala Prasad R , Gauss C Heath , McKinney Hannah N , House Samuel J , Padala Kalpana P
Published: February 2022

Background

Neuropsychiatric symptoms (NPS) are cardinal symptoms of dementia. They are often associated with functional decline, poor quality of life, and caregiver burden. Anecdotal reports have suggested increase in NPS during the COVID pandemic. However, decreased time demands on the caregivers could be hypothesized to have improved relationships and indirectly NPS. There has been limited literature on whether NPS improved or worsened during the current pandemic. The current study examines the prevalence of NPS and changes in NPS profile during the pandemic. Loneliness, cognition, function, and caregiver distress were also studied.

Methods

The COVID Dementia study is an ongoing cross‐sectional study of community dwelling cognitively impaired older adults (N=102). Loneliness was assessed with the 3‐item loneliness questionnaire, cognition with the Tele‐Montreal Cognitive Assessment (T‐MoCA), and functional status with the Functional Activities Questionnaire (FAQ). Neuropsychiatry symptoms including severity and distress were collected using the Neuropsychiatric Inventory (NPI) and change during COVID was also recorded for each symptom.

Results

Mean age was 73.0 (±8.0) years, 96.1% male, 42.2% rural, 75.2% Caucasian, and 24.8% non‐Caucasian. T‐MoCA and FAQ mean scores were 15.2 (±4.6) and 8.0 (±9.3), respectively. Loneliness was prevalent in majority of participants (53.5%). Mean loneliness score was 4.7 (±2.1). Mean NPI total severity and total distress were 7.5 (±6.5) and 10.9 (±8.8), respectively. Irritability and night‐time behavior were most frequently reported symptoms (45.7% each), followed by anxiety (45.3%), and agitation (41.1%).

Majority of the participants reported worsening of neuropsychiatric symptoms during COVID (61.5%). Irritability, agitation, and anxiety was the cluster that was reported as most frequently worsened symptoms during the pandemic followed by depression and apathy cluster (Fig. 1). Among those that reported worsening of neuropsychiatric symptoms, 66.1% noted an increase in ≥ two symptoms.

Conclusions

Older adults with pre‐existent cognitive impairment may be at high risk for loneliness and worsening of neuropsychiatric symptoms during the COVID pandemic. Some NPS might worsen more frequently during the pandemic and need particular attention.
Amygdala tau pathology in preclinical autosomal dominant Alzheimer’s disease
Authors: Sanchez Justin S. , Martinez Jairo E. , Rubinstein Zoe B. , Baena Ana Y. , Vila‐Castelar Clara , Fox‐Fuller Joshua T. , Gatchel Jennifer R. , Ramirez‐Gomez Liliana A. , Aduen Paula , Guzman‐Velez Edmarie , Pluim Celina F. , Jacobs Heidi I.L. , Sperling Reisa A. , Johnson Keith A. , Lopera Francisco , Quiroz Yakeel T.
Published: February 2022

Background

The amygdala has been found to be pathologically affected in early stages of Alzheimer’s disease (AD), with particular amygdala subnuclei being especially vulnerable. We used in vivo positron emission tomography (PET) imaging to examine whether amygdala tau accumulation could be observed in cognitively unimpaired PSEN‐1 mutation carriers who carry an autosomal‐dominant mutation in the Presenilin‐1 (PSEN‐1) gene and are determined to develop dementia in their early 50s. We further aimed to investigate associations between amygdala tau, age, amyloid deposition, and cognition in mutation carriers and non‐carrier family members.

Method

A total of 29 PSEN‐1 mutation carriers (M age = 37.4 +/‐ 5.8 years) and 35 age‐matched non‐carriers (M age = 35.9 +/‐ 5.8 years) were recruited from the Colombia‐Boston (COLBOS) Longitudinal Biomarker Study, which follows Colombian families with autosomal‐dominant AD. Participants underwent PET, using Pittsburgh Compound B to measure mean cortical amyloid‐β and Flortaucipir for regional tau, and episodic memory testing (CERAD Word List Learning). Amygdala subnuclei were automatically segmented with FreeSurfer7. Spearman correlations were used to examine associations among amygdala tau, age, mean amyloid‐β, and memory performance.

Result

Compared to non‐carriers, cognitively unimpaired mutation carriers had greater tau accumulation in the amygdala (p<0.001). Unimpaired carriers had greater tau burden in amygdala compared to neocortical regions (vs. inferior temporal: t=2.3, p=0.03), suggesting early involvement of amygdala tau. Among amygdala subnuclei, basal and accessory basal nuclei had greater tau burden compared to the other subregions (vs. lateral nucleus: t=5.5, p<0.0001) in unimpaired carriers. Greater amygdala tau burden was associated with older age (r=0.649, p<0.0001), greater mean cortical amyloid (r=0.597, p=0.001) and worse memory performance (r=‐0.433, p= 0.019) in carriers. No significant associations were observed in the non‐carrier group.

Conclusion

Amygdala tau burden is associated with greater age, cortical amyloid burden, and worse memory in preclinical autosomal dominant Alzheimer’s disease. These results suggest that amygdala tau accumulation is evident in preclinical Alzheimer’s disease. Future studies should determine if amygdala tau (including subnuclei) can be used as an early indicator of Alzheimer’s disease progression. Longitudinal studies are needed to examine the associations between amygdala tau and onset of neuropsychiatric and behavioral symptoms.
Accounting for lack of representation in dementia research: Generalizing KHANDLE study findings on the prevalence of cognitive impairment to the California older population
Authors: Hayes‐Larson Eleanor , Mobley Taylor M. , Mungas Dan , Seamans Marissa J. , Glymour M. Maria , Gilsanz Paola , DeCarli Charles , Whitmer Rachel A. , Mayeda Elizabeth Rose
Published: February 2022

Introduction

Most dementia studies are not population‐representative; statistical tools can be applied to samples to obtain critically‐needed population‐representative estimates, but are not yet widely used.

Methods

We pooled data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study and the California Behavioral Risk Factor Surveillance System (CA‐BRFSS), a population‐representative study. Using weights accounting for sociodemographic/health differences between KHANDLE and CA‐BRFSS, we estimated cognitive impairment prevalence and age‐ and sex‐adjusted racial/ethnic inequalities in California adults 65+ without prior dementia diagnosis.

Results

After weighting KHANDLE, the estimated cognitive impairment prevalence in California was 20.3% (95% confidence interval 17.8–23.0); unweighted prevalence was 24.8% (23.1%–26.6%). Inequalities (larger prevalences) were observed among Black and Asian groups versus whites.

Discussion

We used a novel statistical approach to estimate population‐representative cognitive impairment prevalence and inequalities. Such statistical tools can help obtain population‐representative estimates from existing studies and inform efforts to reduce racial/ethnic disparities.