bluuebunny/crossref_metadata_2025 huggingface dataset:
Hippocampal volumes across age at different stages of the AD continuum
Authors: Nebreda Alberto , de Frutos Jaisalmer , Cuesta Pablo , Del Cerro‐León Alberto , García‐Colomo Alejandra , Dolado Alberto Marcos , Fuertes Miguel Yus , Maestú Fernando
Published: February 2022

Background

Structural imaging based on magnetic resonance, specifically the measurement of hippocampal volumes, has been found to serve as a useful biomarker to assess the severity and progression of Alzheimer’s disease (AD).

Differences across stages, including the preclinical, where objective signs can not be clinically measured yet, have been reported in many studies. However, it would be useful for clinicians and researchers, not only to have the knowledge that these differences exist and could be used as a biomarker, but also to have access to an age‐related normative barometer for each stage of the disease.

The purpose of this study is to provide a normative database of hippocampal volumes at the different stages of the AD continuum, to provide an easy, age‐adjusted determination of where an individual’s hippocampal volume lies within the distribution, as well as an accessible comparison standpoint for other studies assessing other disorders.

Method

Magnetic resonance imaging scans were performed to 589 Spanish individuals (age 68.15 ± 8.74): 332 healthy controls (HC: age 64.12 ± 8.69), 98 who did not exhibit any objectively measurable neuropsychological impairment, but presented subjective cognitive complaints (SCD: age 72.57 ± 5.40), 143 with mild cognitive impairment (MCI: age 73.50 ± 5.28) and 16 participant with diagnosed AD (AD: age 76.75 ± 5.99).

Result

Percentiles for average hippocampal volume were calculated across age, separately for each diagnostic subgroup. In addition, potential differences attributable to the method of choice were explored, as well as differences associated to sex or presence of different alleles of the gen APOE, related with AD.

Conclusion

This study provides a normative database for hippocampal volume as a function of age, at different stages of the AD continuum, to be used as reference both in clinical and research settings.
Cognitive activity, cognitive function, and structural MRI findings
Authors: Krueger Kristin R. , Wilson Robert S. , Barnes Lisa L. , McAninch Elizabeth A. , Evans Denis A. , DeCarli Charles S. , Fletcher Evan M. , Rajan Kumar B.
Published: February 2022

Background

More frequent engagement in late‐life cognitive activities (e.g. reading, playing games) has been associated with slower cognitive decline in old age. Even after adjusting for neuropathological burden, cognitive activities were associated with less cognitive decline. However, it is not known whether people who engage more frequently in cognitive activities show differences in brain anatomy compared to those who participate less frequently. We tested the hypothesis that brain anatomy, as measured by structural MRI indices, mediates the association of cognitive activities and cognitive decline in old age.

Method

In a sample of 975 participants (60% African American and 60% female) from the Chicago Health and Aging Project, late‐life cognitive activities were collected at baseline; MRI was conducted an average of 7.9 years later. We identified several significant correlations of late‐life cognitive activity with MRI indices (brain regions and cortical thickness) and then used linear mixed‐effects regression models to examine those associations with global cognition. Global cognition was assessed using a standardized measure of episodic memory, perceptual speed, and the MMSE, before and after MRI scans.

Result

Higher frequency of overall cognitive activity was associated with seven brain volumes and two cortical thicknesses, which were associated with global cognitive level. Of those associations, five were associated with cognitive decline and explained about 42% of the cognitive activity association with cognitive decline. Specifically, a higher reading frequency was associated with lower white matter hyperintensity volume (WMH) and third ventricular volume. Higher WMH and third ventricle volumes were also associated with lower global cognition and a faster rate of cognitive decline. We also found that a higher frequency of playing games was positively associated with greater hippocampal and parahippocampal volumes and caudal anterior cingulate thickness in the left hemisphere.

Conclusion

Individuals who engage more frequently in cognitively stimulating activities show differences in brain anatomy compared to those who participate less frequently, as measured by structural MRI. These results suggest that cognitive activities are related to improved structure and function of the brain, thereby shedding light on the well‐established findings that cognitive activities are associated with cognitive decline independent of neuropathologic burden.
Stress biomarkers as outcomes for support groups for people with memory loss and their caregivers (SO CALM)
Authors: Yang Mia , Espeland Mark A , Berga Sarah , Clarke Philip , Ivers Nathaniel N , Shaw Edward G , Taylor Robert N , Hugenschmidt Christina E
Published: February 2022

Background

Despite the significant burden neuropsychiatric symptoms impose, rigorous research on behavioral interventions to address anxiety, apathy, and depression in people with dementia is limited, especially in those with mid‐ to late‐stage dementia. The Memory Counseling Program (MCP) at Wake Forest School of Medicine offers multi‐tiered support groups that are unique because 1) they are 10‐week, structured groups rather than open, monthly support groups and 2) they include the person living with dementia (PLWD) rather than targeting the caregiver alone.

Method

We measured quantitative biomarkers of stress to complement self‐reports at baseline, prior to initiation of support groups, with follow‐up visit within 10 days of last support group. We used paired t‐tests to examine the differences between pre‐group and post‐group measures for caregivers (Perceived Stress Scale, urinary cortisol, and allostatic load) and for PLWD (Apathy Evaluation Scale, urinary cortisol, and allostatic load). Allostatic load is the burden of chronic and repeated exposure to stress and a marker of stress resilience derived from a combination of labs, blood pressure, waist‐to‐hip ratio, and body‐mass index.

Result

Among 20 participants (1:1 caregiver and PLWD), self‐reports of Perceived Stress Scale and Apathy Evaluation Scales did not change after support group participation, however biomarkers of urinary cortisol and allostatic load decreased significantly after group participation. Among 10 caregivers, urinary cortisol changed from baseline mean 15.6µg/L (SD 12.7) to follow‐up mean 10.3 µg/L (SD 11.4, p<0.05) and allostatic load from baseline mean 5.6 (SD 2.1) to follow‐up mean 4.4 (SD 1.4, p<0.06). Among 10 PLWD, their mean baseline urinary cortisol 22 µg/L (SD 18.3) decreased to 9.8 µg/L (SD 8.0) at follow up and their allostatic load decreased from 5.9 (SD 2.1) at baseline to 5.1 (SD 1.5, p<0.05) at follow up.

Conclusion

The Wake Forest Memory Counseling program non‐pharmacologic 10‐week structured support groups may be able to reduce objective stress biomarkers for both caregivers and PLWD. Future studies should test structured support groups with an active attention control in a prospective manner.
Caregiving management styles and utilization of formal care services among dementia caregivers
Authors: Leggett Amanda N , Connell Cathleen M , Gitlin Laura N , Kales Helen C
Published: February 2022

Background

While dementia caregivers report need for assistance, formal service utilization remains low (apprx. 25%). Research suggests demographic characteristics associated with service use, but caregivers’ cognitive and behavioral approach to care has not been considered. Prior work by this team has identified five distinct caregiving styles through qualitative analysis: “Externalizers” (superficial understanding, self‐focused, anger, frustration), “Individualists” (go it alone, emotionally removed), “Learners” (recognize need to change approach but stuck, emotionally turbulent), “Nurturers” (positive affect, empathy, natural mastery), and “Adapters” (arsenal of acquired management strategies, adaptable). We examine variation in formal care service utilization of the caregiving styles and hypothesize that styles showing greater adaptation to the care role (Adapters, Nurturers) will be more likely to utilize formal care services. We also explore reported barriers to use of formal services among those caregivers reporting non‐use.

Method

Participants included 100 primary caregivers for a person living with dementia (PLwD) who were 64 years old on average, 74% female, and 18% non‐White. Use (vs. non‐use) of formal services was a dichotomous outcome in a logistic regression with caregiving style classifications as the key predictors also adjusting for caregiver demographics, length of care, co‐residence, and dementia severity.

Result

Rates of service utilization varied by caregiving style (20%‐70%). Relative to nurturers (style least likely to use formal services), adapters had greater odds of utilizing formal services (OR=14.4, 95% CI= 1.8‐115.1). Additionally, caregivers who were older and providing care for a PLwD with greater dementia severity had greater odds of formal service use, while caregivers living with the PLwD reported lower odds of service use. Among those not using services, there were not significant differences in barriers to use (e.g. expense) across styles, however, over half cited not needing the assistance.

Conclusion

Being an Adapter was significantly associated with service use suggesting that certain caregivers may have greater comfort in accessing such services. Styles showing less adaptability and more rigidity in care approach (e.g. Externalists, Individualists) may not recognize need for formal supports or benefit from support in selecting assistance that meets their needs. Future work may consider measuring for caregiving styles before making service recommendations.
Microstructural mapping of dentate gyrus pathology in Alzheimer’s disease: A 16.4 Tesla magnetic resonance imaging study
Authors: Shih Nien‐Chu , Jones Kymry T. , Kurniawan Nyoman D. , Wong Eellen , Miller Carol A. , Clark Kristi A. , Chui Helena C. , Sepehrband Farshid
Published: February 2022

Background

The dentate gyrus (DG) is an important part of the hippocampal structure and it comprises the molecular (ML), granular cell (GCL), and polymorphic layers (PL). Impaired DG is associated with Alzheimer’s disease (AD) pathology. MRI provides general structural information for the clinical diagnosis, but assessing subtle cellular pathological changes still requires histological observation. Here, we performed ultra‐high‐resolution MRI to investigate the correlation between MRI signals in DG and histological measurements of AD pathology.

Method

Postmortem hippocampi tissues were used (5 cognitive normal, 5 AD; from USC ADRC). Approximately 2 cm3 of tissue dissected from the anterior hippocampus was scanned using 16.4T MRI, the adjacent tissue was processed for immunohistochemistry. Quantitative ex vivo MRI were acquired at 50 µm3 (T2, T2* and SWI). Multi‐shell diffusion MRI were acquired at 150 µm3 (scan time=72hrs). ITK‐SNAP was used to delineate ML, GCL, and PL regions of the DG; and Fiji software to divide histological images of ML, GCL, and PL into twenty equally sized regions of interest (Figure1A), guided by the Allen human brain atlas. Quantitative and morphometric features of DG subregions were calculated from MRI. Histological data was analyzed to measure cell count from H&E slides, neurofilament density and tau pathology from NF160 and AT8 stained slides, respectively (Figure1B).

Result

T2‐map (Figure1C) was positively correlated with neurofilament density in ML (R=0.66, p=0.038), PL (R=0.75, p=0.033) and negatively correlated with p‐tau density (ML:R=−0.60, p=0.064; PL:R=−0.61, p=0.062). R2‐map (ML:R=−0.78, p=0.008; PL:R=−0.67, p=0.032 ) and SWI (ML:R=−0.79, p=0.006; PL:−0.80, p=0.005) was negatively correlated with neurofilament. R2 also had positive correlations with p‐tau density (ML:R=0.70, p=0.02; PL:R=0.6, p=0.068). Finally, diffusion decay rate was significantly correlated with neurofilament in PL (R=0.76; p=0.012).

Conclusion

Results suggest that quantitative MRI is sensitive to subtle neurite changes within the hippocampal formation, which could be used to assess the connectivity changes in the course of AD. This could also provide insight about the mechanism of AD progression if translated in vivo. The quantitative measurement of the connectivity alteration could also have early diagnosis value, given that recent studies have shown that connectivity changes precede cortical atrophy in AD.
Amyloid and tau PET imaging studies as a clinical prognostic marker in Alzheimer’s disease
Authors: Kim Han‐Kyeol , Baek Min Seok , Lee Jae Hoon , Chun Joong‐Hyun , Ryu Young Hoon , Cho Hanna , Lyoo Chul Hyoung
Published: February 2022

Background

To investigate prognostic value of amyloid (A) and tau (T) imaging biomarkers in a long term follow up cohort study.

Method

We included 273 AD spectrum participants [96 cognitive unimpaired (CU), 106 mild cognitive impairment (MCI) and 71 AD dementia (DEM)] who completed 18F‐florbetaben, 18F‐flortaucipir PET and T1‐weighted MRI. Global cortical standardized uptake value ratios (SUVR) of 18F‐florbetaben, temporal meta‐region‐of‐interest SUVR of 18F‐flortaucipir and hippocampal atrophy of T1‐weighted MRI were used to define AT(N) classification. Longitudinal cognitive change was evaluated by repeated Mini‐Mental State Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR‐SB). Participants were categorized according to their A/T imaging biomarker, 18F‐florbetaben PET positive/negative (A+/A‐) and 18F‐flortaucipir PET positive/negative (T+/T‐) profiles. For measuring prognosis, we investigated the nursing care facility admission rate for all participants and the AD conversion rate for CU and MCI over 60 months.

Result

Participants were included CU (77/96 A‐T‐, 1/96 A‐T+, 11/96 A+T‐ and 7/96 A+T+), MCI (59/106 A‐T‐, 2/106 A‐T+, 18/106 A+T‐ and 27/106 A+T+) and DEM (20/71 A‐T‐, 1/71 A‐T+, 16/71 A+T‐ and 34/71 A+T+). Annual cognitive function change of all participants was correlated with A+ (MMSE: B=‐0.5944, p <0.000; CDR‐SB: B=0.6288, p <0.000), T+ (MMSE: ‐0.8187, p <0.000; CDR‐SB: B=0.7524, p <0.000), hippocampal atrophy (MMSE: B=‐0.3940, p <0.000; CDR‐SB: B=0.5577, p <0.000) and A+T+ compared with A‐T‐ (MMSE: B=‐0.8917, p <0.000; CDR‐SB: 0.8680, p <0.000, Figure 1). Admission rate of nursing care facility of all participants was higher with A+ (HR=2.37, p =0.026), T+ (HR=2.65, p =0.006) and A+T+ (HR=3.06, p=0.006). AD conversion rate in CU and MCI (n=202) was higher with A+ (HR=2.98, p=0.003), T+ (HR=3.19, p<0.000) and A+T+ (HR=3.897, p <0.000, Figure 2).

Conclusion

A/T imaging biomarkers have prognostic value for annual cognitive decline rate, anticipating admission rates to nursing care facility, and AD conversion rate.
Correlation between the counts and volume of cerebral microbleeds and cognitive function in patients with cerebral small vessel disease
Authors: Zhao Hui , Shao Peng Fei , Shao Pengfei
Published: February 2022

Background

Cerebral small vessel disease(CSVD)is a primary reason of vascular cognitive impairment in elderly population. One of the neuroimaging markers of CSVD is cerebral microbleeds(CMBs). However, little is known about the quantifed volumetry analysis of CMBs and its correlation with cognitve function in these CSVD patients.

Method

A total of 207 individuals were recruited, including CMBs with cognitive impairment (CMBs‐CI) (n=73), CMBs without cognitive impairment (CMBs‐non‐CI) (n=68) and normal controls (NC) (n=66). All underwent neuro‐psychological testing and 3.0T MRI Scan. Accubrain IV 1.0 kit was used to investigate the count and the quantifed volumetry analysis of CMBs. Multivariate logistic regression analysis was applied to assess the independent influencing factors of cognitive impairment. Multiple linear regression equation was performed to analyze the independent influencing factors of cognitive score. Finally, we used receiver operating characteristic (ROC) curve to evaluate the predictive value of the CMBs count and volume on cognitive impairment.

Result

Compared with CMBs‐non‐CI and NC group, the number and volumes(lg: logarithmic transformation) of CMBs in CMBs‐CI group were significantly increased() Multivariate logistic regression analysis showed that the number and volume of CMBs were independent risk factors for cognitive impairment. (OR= 1.498, 95%CI: 1.282‐1.750, P < 0.001; OR=7.640, 95%CI: 3.982‐11.656, P < 0.001). But there was no significant correlation between the counts of CMBs and cognitive scores (ß = ‐ 0.020, P = 0.383), while the volume of CMBs were negatively correlated with the cognitive ability( ß= ‐ 0.582, P<0.001). ROC curve analysis of the amount of CMBs in predicting cognitive impairment was 0.694(Area under the curve, AUC) (95%CI: 0.611‐0.769, 3(optimal threshold) 47.95%( sensitivity) and 89.71%(specificity); ROC curve analysis of the volume of CMBs in predicting cognitive impairment was 0.886 (Area under the curve, AUC) (95%CI: 0.822‐0.933),14.125mm3(optimal threshold) 75.34% (sensitivity) and 86.76% (specificity) correspondingly. The difference between the two areas under the ROC curves was 0.192 (95% CI:0.090‐0.294, P = 0.001).

Conclusion

In CSVD patients, there is a significant correlation between CMBs and poor cognitive performance. Our results suggested that compared with the count of CMBs, the volume of CMBs was hope to be a more liable predictor to the progress of cognitve impairment.
COVID‐19: Prevalence evaluation of anxiety, depression, and burden in Argentine family caregivers
Authors: Tartaglini María Florencia , Hermida Paula Daniela , Ofman Silvia Deborah , Feldberg Carolina , Heisecke Silvina Lidia , Somale Verónica , Caruso Diego
Published: February 2022

Background

Since WHO declaration of the COVID‐19 pandemic, the Argentine Ministry of Health considered pregnant women, over 60 years old adults, and people suffering from chronic diseases as cohorts at risk.

In this context, older adults diagnosed with neurodegenerative diseases as well as their family caregivers were affected by radical changes in the dynamics of health care and a consequent limitation of help resources.

The objective of this study is to estimate the prevalence of anxiety, geriatric depression, and burden in Argentine family caregivers within the COVID‐19 pandemic context. It also aims at evaluating the correlation between these variables.

Method

Design: Non‐experimental, descriptive‐correlational study. Procedure: Between April and August 2020, an online survey was administered to 180 senescent family caregivers of both sexes, living in Argentina. Instruments: Ad‐hoc sociodemographic and psychosocial questionnaire, Generalized Anxiety Scale (GAD‐7), Yesavage Geriatric Depression Questionnaire (GDS‐VE), and Zarit Caregiver Burden Scale (Argentine validated version).

Result

The study cohort mean age was 67 years old (sd = 6), 81% were women, and 56% were daugthers of the assisted family member. Regarding analyzed variables, 46% of the survey respondents presented depression, 68% caregiver burden, and 71% anxiety. A positive, moderate correlation was observed between geriatric depression and anxiety (“r”: .468, p: .000).

Conclusion

The results provide empirical evidence of the impact of care tasks on emotions of family caregivers within the context of the COVID‐19 pandemic. These findings invite devising necessary and possible anticipated intervention strategies, specially facing the second wave of the pandemic.
Quantitative analysis of amyloid PET or FDG‐PET showed differences in aMCI to AD convert group
Authors: Chong Ari , Ha Jung‐Min , Chung Ji Yeon , Kim Hoowon , Choo Il Han
Published: February 2022

Background

In this study with amnestic mild cognitive impairment impairment (aMCI) subjects, we compared Alzheimer’s disease (AD) converter and non‐converter in findings of F‐18 FDG PET/CT (FDG PET), F‐18 Florbetaben PET/CT (amyloid PET) and other clinical features.

Method

Patients with aMCI who underwent both FDG PET and amyloid PET were included. They underwent neuropsychological test, blood test and apoE4 test as well. After follow‐up, AD converter and non‐converter were determined by neurologists. Comparison between AD converter and non‐converter groups were done with FDG PET variables (SUVR), amyloid PET variables (SUVR, RCTU, and conclusion of visual reading), neuropsychological variables (including classification of single domain or multi domain) and other laboratory results. MIM software was used for SUVR. We used P<0.05 as statistical significance.

Result

Total 45 subjects of aMCI (age range from 63 to 89 years, M:F=26:19) were enrolled. After follow up (range from 11.6 to 41.3 months), AD convert group (n=12) and non‐convert group (n=33) were determined. For FDG, there were regions with lower FDG SUVR in AD converter group than non‐converter group (both angular gyrus, both posterior cingulate gyrus, left precuneus, let temporal pole, left inferior temporal gyrus and left inferior medial frontal gyrus).For amyloid, analysis with conclusion by visual analysis (positive vs negative) did not show significant differences. However, quantitative analysis with amyloid SUVR showed that higher amyloid SUVR in AD converter group than non‐converter group (in left angular gyrus, left fusiform gyrus, left inferior temporal gyrus, left lateral temporal lobe and right paracentral lobule). RCTU scores were also higher in AD converter group (in bilateral temporal, frontal, parietal and total sum scores of RCTU). AD converter group also showed worse cognitive function at first evaluation (sum of boxes, RCFT delayed recall and domain memory) AD converter showed higher serum glucose level and triglyceride.There was not significant difference in follow‐up interval, education, age, sex, domain (single domain/multi‐domain), apoE4 carrier/non‐carrier/apoE4 heterogeneity (non‐carrier, homozygotes and heterozygotes). RCTU for left frontal lobe showed significant odd ratio (3.85).

Conclusion

Quantitative variables of FDG PET and amyloid PET showed different results between AD conveter and nonconverter groups in aMCI.
Alzheimer's disease and cerebrovascular disease biomarkers in older adults with mild cognitive impairment or major depressive disorder
Authors: Golas Angela C. , Salwierz Patrick , Rajji Tarek K. , Bowie Christopher R. , Butters Meryl A. , Fischer Corinne E. , Flint Alastair , Herrmann Nathan , Mah Linda , Mulsant Benoit H. , Pollock Bruce G. , Taghdiri Foad , Tartaglia Maria Carmela
Published: February 2022

Background

Mild Cognitive Impairment (MCI) and Major Depressive Disorder (MDD) are independently associated with increased risk of dementia. Cerebrospinal fluid (CSF) and neuroimaging biomarkers can help to elucidate the etiology of cognitive impairment. We compared CSF biomarker profiles of Alzheimer’s disease (AD) and white matter hyperintensities (WMH) across three groups: MCI, MDD, or comorbid MCI+MDD.

Method

We measured CSF total tau, p‐tau, amyloid‐β42, using a sandwich ELISA method (Innotest, Fujirebio), and calculated p‐tau/amyloid‐β42 ratio in 31 participants diagnosed with MCI (N=13), MDD (N=7), or both MCI and MDD (N=11) enrolled in the Preventing Alzheimer’s dementia with cognitive remediation plus transcranial direct current stimulation in mild cognitive impairment and depression (PACt‐MD) study. All diagnoses were made in accordance with NIA‐AA and DSM 5 criteria. Participants with p‐tau > 68 pg/mL and ATI < 0.8 were considered AD (+). WMH were quantified on T2‐weighted magnetic resonance images in 27 of the participants. We compared CSF AD biomarkers across diagnostic groups. We then compared cognitive performance and WMH in those with AD (+) versus AD (‐) CSF biomarkers.

Result

9/31 participants exhibited AD (+) CSF: 7/13 with MCI and 2/11 with MCI+MDD. Participants with AD (+) CSF showed more impairment in verbal memory, working memory, language, and overall cognition than those with AD (‐) CSF (p=0.02, p=0.04, p=0.04, and p=0.03, respectively). 26/27 (96%) participants exhibited moderate to severe WMH irrespective of diagnosis or AD biomarker status.

Conclusion

Few participants in our sample with MDD had an AD (+) CSF biomarker profile, despite a neurocognitive profile of MCI. All participants with AD (‐) CSF had moderate to severe WMH, including those with MDD alone. Further investigation should determine whether volume or distribution of WMH contribute to cognitive impairment or depression in MCI patients who have an AD (‐) CSF biomarker profile.
The use of music at home reduces symptoms of dementia and caregiver distress
Authors: Ray Kendra , Mittelman Mary S
Published: February 2022

Background

As Alzheimer’s disease progresses, neuropsychiatric symptoms, particularly those common in the middle stages of the disease can be increasingly stressful for family caregivers. Music‐based interventions, when personalized and added to daily caregiving routines, have been shown to reduce occurrences or severity of these undesirable symptoms. In this study, family caregivers learned to implement music interventions to mitigate the impact of challenging behaviors.

Method

We present the results of interim analyses of the results for the first group of participants in a study of a psychoeducational, music‐based intervention for family caregivers. Eighteen NYC‐based family caregivers participated in a 6‐week program either in person (pre‐COVID) or online with a music therapist. Following each weekly one‐hour workshop, caregivers were asked to utilize music interventions such as singing during care, listening to personalized playlists on Spotify, or facilitating music and movement with their care recipient. The Neuropsychiatric Inventory‐Questionnaire was used to measure twelve neuropsychiatric domains and measure caregiver distress before and after the 6‐week intervention. Paired sample t‐tests were used to measure change in these outcomes for caregiver and care recipient. A Pearson correlation coefficient was used to estimate the relationship between symptoms of dementia and caregiver distress.

Results

There was a significant improvement in both neuropsychiatric domains in care recipients from before (M= 12.23 ± 6.26) the six‐week program to after (7.83 ± 3.51), p =.028, and in caregiver distress prior (M=14.88 ± 9.36) to after (8.68 ± 5.95), p =.03. The symptoms most reported to contribute to caregiver distress were irritability (n=12), night‐time behaviors (n=12), and agitation (n=11). Neuropsychiatric symptoms and caregiver distress were found to be strongly correlated, r (16) =.64, p=.004.

Conclusion

Preliminary results of this ongoing study indicate that caregivers who implement music‐based interventions can both reduce undesirable symptoms of dementia and thereby their own distress.
Alzheimer’s disease resemblance atrophy index in the identification of Alzheimer's disease with mild dementia
Authors: Fan Xiang , Zhao Lei , Liu Wanting , Cai Yuan , Luo Yishan , Shi Lin , Mok Vincent C.T.
Published: February 2022

Background

Alzheimer’s disease (AD) resemblance atrophy index (AD‐RAI) is an MRI‐based biomarker that was developed using a machine learning technology that combines multi‐region MRI features to reflect the characteristic atrophy pattern of AD. It was validated to be accurate in predicting conversion from mild cognitive impairment to dementia (1) and in identifying AD patients with moderate dementia. We aimed to compare the performance of AD‐RAI with various MRI‐based quantitative medial temporal lobe atrophy (MTA) measures in identifying AD with mild dementia.

Method

We reviewed 3489 subjects in 3 datasets, i.e., ADNI (n=1529), AIBL (n=862), and OASIS 3 (n=1098). We selected subjects aged 65 to 85 years with clinical dementia rating scale of 1. Among potential eligible AD subjects with mild dementia who also had amyloid data based on either cerebrospinal fluid analysis or positron emission tomography (n=73), we further excluded those who were amyloid negative (n=5). A total of 121 AD subjects with mild dementia and 691 age‐matched elderly normal controls (NC) were eventually recruited. An automated computational tool, AccuBrain, was used to generate the following imaging biomarkers: hippocampal volume (HV), hippocampal fraction (HF), quantitative MTA (QMTA) and AD‐RAI. We compared the following performance metrics in identifying AD with mild dementia for each of the imaging biomarkers: area under curve (AUC) of receiver operating characteristic (ROC) curve, sensitivity, specificity and balanced accuracy.

Result

Regarding the ROC analysis, the AD‐RAI performed the best in identifying mild AD from NC (AUC=0.92, sensitivity=0.88 and balanced accuracy=0.83), followed by QMTA and HV/ HF (Table 1 and Figure 1).

Conclusion

AD‐RAI outperformed other MRI‐based quantitative MTA measures in identifying AD with mild dementia. Since majority of AD patients when they first presented to memory clinic are at the stage of mild dementia, AD‐RAI may aid accurate diagnosis of AD in clinical practice. Reference: 1) Zhao L, Luo Y, Lew D, Liu W, Au L, Mok V, et al. Risk estimation before progression to mild cognitive impairment and Alzheimer's disease: an AD resemblance atrophy index. Aging (Albany NY). 2019;11(16):6217‐36.
Music interventions for dementia and depression in elderly care (MIDDEL): The Australian part of an international cluster randomised controlled trial
Authors: Baker Felicity , Lee Young‐Eun C , Sousa Tanara , Stretton‐Smith Phoebe , Clark Imogen , Sveinsdottir Vigdis , Geretsegger Monika , Gold Christian
Published: February 2022

Background

Dementia and depression are highly prevalent, comorbid conditions in older adults residing in care homes and are associated with individual distress and associated challenges for care staff. Music‐based interventions are widely used and potentially effective nonpharmacological interventions, due to the relative preservation of the ability of people with dementia to respond to music even with disease progression. However, there is a lack of large‐scale studies evaluating the effectiveness of music‐based interventions in dementia care. Music Interventions for Dementia and Depression in the Elderly (MIDDEL) is the first large‐scale international cluster‐randomised controlled trial to investigate the effectiveness of small group music therapy (GMT), recreational choir singing (RCS) and their combination on levels of depression in residents with dementia. The trial is currently being conducted across six countries, and this presentation will outline the study outcomes from the Australian arm of the trial.

Method

Between June 2018 and November 2019, 20 care home units were randomised to music interventions (GMT, RCS, GMT and RCS) or standard care delivered over 6 months. The primary outcome was level of depression as measured by the Montgomery‐Asberg Depression Rating Scale (MADRS). Secondary outcomes included neuropsychiatric symptoms, quality of life, care staff burden and adverse events collected at baseline, 3‐months, 6‐months and 12‐months post‐randomisation. Outcomes were analysed as intention‐to‐treat, per‐protocol, and with exploratory predictor analyses.

Results

318 participants (215 female; 103 male) aged 65 years or more with diagnoses of dementia and at least mild depressive symptoms (as defined by score of 8 or above on MADRS) residing in care homes were recruited. In addition, 131 care staff (108 female; 23 male) answered questions regarding perceived care burden to search for potential ripple effects of the music interventions. We will present the main findings of the study including the predictive effects of clinical characteristics on efficacy.

Conclusion

The presentation will include discussion of contextual factors and conditions that support efficacy, and clinical implications for safety and quality of life for people with dementia living in care homes.
Default mode network dissociation linking cerebral beta amyloid retention and depression in cognitively normal older adults
Authors: Lim Hyun Kook , Wang Shengmin
Published: February 2022

Background

To date, cerebral beta amyloid (Aß) deposition and late‐life depression (LLD) are known to be associated with trajectory of Alzheimer’s disease (AD). However, their neurobiological link is not clear. Although previous studies showed aberrant functional connectivity (FC) change of default mode network (DMN) in early Aß deposition and LLD respectively, its mediating role is not elucidated. The aim of this study is to investigate distinctive association pattern of DMN FC linking LLD and Aß retention in the cognitively normal older adults.

Method

Two hundred thirty‐five cognitively normal older adults with (N=118) and without depression (N=117) underwent resting state functional magnetic resonance image and 18F‐Flutemetamol positron emission tomography. We investigated associations among Aß burden, depression, and DMN FC.

Result

Independent component analysis showed increased anterior DMN FC and decreased posterior DMN FC in depression group compared with no depression group. Global cerebral Aß retention correlated positively with anterior and negatively with posterior DMN FC. Anterior DMN FCs were positively correlated with depression severity whereas posterior DMN FCs were negatively correlated with cognitive function. In addition, effect of global cerebral Aß retention on depression severity was mediated by subgenual anterior cingulate FC.

Conclusion

Our results of anterior and posterior DMN FC dissociation pattern might play pivotal role in linking cerebral Aß pathology and LLD in the course of AD progression. Further longitudinal studies would be needed to confirm causal relationships between cerebral Aß retention and LLD.
Process evaluation of a culturally tailored, mental health program for Vietnamese American dementia caregivers
Authors: Park Van Ta , Bui Nhat Minh , Vuong Quyen , Yeo Gwen , Tiet Quyen Q , Gallagher‐Thompson Dolores
Published: February 2022

Background

Dementia caregivers (DCGs) have poorer mental health compared to the general population, but research on responding to those needs in culturally diverse populations such as Vietnamese American (VA) DCGs is limited. This study describes the process evaluation of a culturally tailored, evidence‐based skill‐building program, Our Family Journey (OFJ), to reduce stress and depression among VA DCGs in San Jose, California, USA.

Method

We examined process components (program fidelity, dose delivered, dose received, and reach) of an intervention for 60 VA DCGs who were randomly assigned to either the intervention, (OFJ; n=30) or to the control condition (written dementia caregiving information; n=30).

Result

Translated from a 6‐weeks evidence‐based program, the culturally tailored, Vietnamese OFJ was reduced to 4 weeks for optimal attendance and participation (program fidelity). Modifications in content and process were developed with input from the creator of OFJ and a large community‐based organization serving VAs. Cultural tailoring included delivering the program in Vietnamese, with material incorporating culturally appropriate values and activities. For example, pleasant activities included cooking Vietnamese food and doing karaoke rather than the original program’s emphasis on solitary activities (e.g., reading a book). Discussions about filial piety and stigma were included, as these topics were very relevant to VAs (program fidelity). All 4 sessions were conducted as planned for each of the six OFJ cohorts (mean number of participants per cohort was 4.8) (dose delivered and dose received). Accommodations were provided for DCGs as needed – e.g., when they could not attend a session, they were offered the make‐up session. A total of 112 interested persons contacted research staff; 88 were eligible to participate. Final enrollment was 60 caregivers (reach). Feedback from participants included: expanding eligibility criteria to include other family caregivers; incorporating more cultural aspects (e.g., spirituality); and expanding educational topics of interest to DCGs (e.g., age‐related health changes and transitions of care.)

Conclusion

The OFJ program is the first randomized controlled trial of a culturally tailored evidence‐based intervention with VA DCGs in the US. Future research should replicate this promising program with suggested modifications to continue to meet the unmet needs of VA DCGs.
A new tool for fusioning PET and omics data
Authors: Povala Guilherme , De Bastiani Marco Antônio , Brum Wagner Scheeren , Ferreira Pamela C.L. , Bellaver Bruna , Zatt Bruno , Zimmer Eduardo R.
Published: February 2022

Background

Positron emission tomography (PET) imaging plays a key role in the diagnosis of Alzheimer’s disease (AD). The idea of integrating PET and omics data can provide blood‐new insights about AD pathophysiology. In this context, state‐of‐the‐art techniques such as transcriptomics hold much potential for discovering altered biological processes in AD and other neurodegenerative diseases. However, tools for integrating PET and omics data are still unexplored. Here, we developed a new method that combines blood transcriptomics with PET data. We hypothesized that our method will allow advancing our understanding of AD neurobiology and potentially unravel clinically relevant new peripheral biomarkers.

Method

Imaging and transcriptomics data were acquired from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Microarray gene expression profiling from blood samples of 69 cognitively unimpaired (CU) and 158 mild cognitively impaired (MCI) individuals were submitted to differential expression (DE) analysis using the limma R package. Genes obtained from DE analysis were selected to undergo integration with [18F]Fluorodeoxyglucose (FDG)‐PET images using voxel‐wise generalized linear regression (GLR) models adjusted for age, gender and APOEε4 (RMINC package).

Result

The DE analysis resulted in 1232 differentially expressed genes (DEGs) in CU vs MCI individuals (p‐value<0.05). For each DEG, the GLR computed the voxel‐wise association between FDG‐PET and gene expression, resulting in t‐value maps. Afterward, only gray matter voxels presenting absolute t‐values higher than 2.3 were preserved. Then, the volumes of interest (VOI) presenting at least 30% of voxels with a significant correlation obtained from the t‐value map were filtered, which resulted in 268 significantly correlated genes throughout the brain. Next, a map of DEG counts in each VOI (Figure 1a) and maps with the proportion of up‐ (Figure 1b) and downregulated DEGs (Figure 1c) were created. An overall map of altered VOIs is displayed in Figure 1d. Finally, we identified that the putamen was the VOI with the most significantly correlated DEGs.

Conclusion

Here we presented a pipeline for integrating PET neuroimaging with transcriptomics data. This method allows for the identification of potential novel biomarkers and altered peripheral biological pathways.
Cognition and hippocampal volume in amyloid positive clinically normal adults: Results from the A4 study
Authors: Petersen Kellen , Grober Ellen , Lipton Richard B. , Sperling Reisa A. , Buckley Rachel F. , Ezzati Ali
Published: February 2022

Background

Recent studies suggests that sex and genomic differences influence the earliest neuropsychological and pathologic manifestations of Alzheimer’s disease (AD). The relationship between individual cognitive status and the degree of neurodegeneration, and the influence of sex and APOE4 status on these relationships, remains uncertain. Using cross‐sectional data, we investigate the association between cognition in preclinical AD and adjusted hippocampal volume (HVa), a proxy for neurodegeneration related to memory.

Method

Participants included 1169 cognitively unimpaired individuals aged 65 to 85 screened in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study, who were amyloid positive, completed neuropsychological evaluations, and had APOE4 genotyping and structural MRIs. HVa was obtained by residual correction to account for sex differences in hippocampal and intracranial volumes. Association between HVa and cognition was evaluated using a two‐sample t‐test for the whole sample and subsamples stratified by sex and APOE4 status.

Result

In the whole sample, lower HVa was linked with worse performance on measures of memory (Free Recall (FR): p=0.030; Total Recall 96 (TR96): p= 0.032), mental status (Mini‐Mental State Examination (MMSE): p= 0.048), executive functioning (Digit Symbol Substitution (DSS): p<0.001), and the Preclinical Alzheimer’s Cognitive Composite (PACC: p<0.001) (Figure 1, Table 1). Based on comparison of effect sizes between groups, DSS and PACC were the most impacted measures to early neurodegeneration‐related cognitive decline while PACC and TR96 were the most impacted tests to advanced neurodegeneration‐related cognitive decline (Table 1). In multiple regression, adjusting for age and education, all cognitive measures except MMSE were associated with HVa among women (FR: p=0.012; TR96: p=0.007; Delayed Logical Memory (DLM): p=0.014; DSS: p<0.001; PACC: p<0.001), but not men. Among APOE4 positive individuals, all cognitive measures except MMSE were associated with HVa (FR: p=0.016; TR96: p=0.006; DLM: p=0.009; DSS: p=0.002; PACC: p<0.001), however, there was no association between cognition and HVa in APOE4 negative individuals.

Conclusion

While all cognitive measures were significantly associated with neurodegeneration in amyloid positive individuals, cognitive tests show different sensitivities in detecting early or late signs of neurodegeneration as measured by HVa. There are clear differences in association between cognition and neurodegeneration based on sex and APOE4 status.
Diffusion models reveal white matter microstructural changes with aging, pathology, and cognition
Authors: Pillai Sheela Kumari Raghavan , Reid Robert I. , Przybelski Scott A. , Lesnick Timothy G. , Graff‐Radford Jonathan , Schwarz Christopher G. , Knopman David S. , Mielke Michelle M. , Machulda Mary M. , Petersen Ronald C. , Jack Clifford R. , Vemuri Prashanthi
Published: February 2022

Background

White matter microstructure undergoes progressive changes during the life‐span but the neurobiological underpinnings related to aging and disease remains unclear. We used an advanced diffusion MRI, Neurite Orientation Dispersion and Density Imaging (NODDI), to investigate the microstructural alterations due to demographics, common age‐related pathological processes (amyloid, tau, and white matter hyperintensities (WMH)), and cognition. We also compared NODDI findings to the older Diffusion Tensor Imaging (DTI) model based findings.

Method

328 participants (264 cognitively unimpaired, 57 mild cognitive impairment (MCI), and 7 dementia with a mean age of 68.3 ±13.1 years) from the Mayo Clinic Study of Aging with multi‐shell diffusion imaging, FLAIR‐MRI as well as amyloid and tau PET scans were included in this study. White matter (WM) tract level diffusion measures (Figure 1) were calculated from DTI and NODDI. Pearson correlation and multiple linear regression analyses were performed with diffusion measures as the outcome and age, sex, education/occupation, WMH, amyloid, and tau as predictors. Analyses were also performed with each dMRI measure as a predictor of cognitive outcomes.

Result

Age and WMH were the strongest predictors of all WM diffusion measures with low associations with amyloid and tau (Figure 1). However, neurite density decrease from NODDI was observed with amyloidosis specifically in the temporal lobes (Figure 2). WM integrity (mean diffusivity and free water) in the corpus callosum showed the greatest associations with cognitive measures (Table 1). All diffusion measures provided information about WM aging and WM disease processes and were associated with cognition.

Conclusion

NODDI and DTI are two different biophysical models that provide distinct information about variation in WM microstructural integrity. NODDI provides additional information about synaptic density, organization, and free water content which may aid in providing mechanistic insights into disease progression.
Development and evaluation of an unbiased, high‐resolution and detail‐preserving structural T1‐weighted template for use in studies on older adults
Authors: Ridwan Abdur Raquib , Wu Yingjuan , Niaz Mohammad Rakeen , Qi Xiaoxiao , Bennett David A. , Arfanakis Konstantinos
Published: February 2022

Background

Construction of an optimal T1‐weighted template for older adults often requires selection of a target anatomy for nonlinear‐registrations, however a poorly chosen template may introduce bias due to large structural discrepancies between template and subjects used for template construction resulting in misregistration and thereby loss of important anatomical details. Moreover, large structural brain differences across older adults may introduce registration errors. Here, a minimum‐deformation T1‐weighted template specifically for studies on older‐adults was developed using a sparse, patch‐based, detail‐preserving template construction method that minimizes biases.

Method

This work used T1‐weighted brain MRI data obtained from 400 non‐demented older adults (65‐95 years of age, male:female=1:1) participating in longitudinal cohort studies of aging. The template construction scheme involved a reference‐free groupwise normalization utilizing affine transformations followed by ANTs SyGN groupwise normalization utilizing a weighted average scheme in every iteration. Finally a patch‐based tissue‐guided sparse‐representation approach was employed to generate the new template (Fig. 1). The new template was compared to the weighted average template and other 0.5mm templates through visual inspection, in terms of image sharpness by means of the normalized power spectral density and also inter‐subject spatial normalization accuracy achieved when used as references for normalization of T1‐weighted data from 202 ADNI3 participants. Normalization accuracy was assessed for each template by means of the average pairwise normalized cross correlation, average pairwise Jaccard index and average log‐Jacobian determinant of ADNI3 participants.

Result

The new template maintained anatomical consistency and exhibited higher image sharpness as demonstrated by larger high spatial frequency content in the normalized power spectra compared to other templates (Fig. 2 & Fig. 3A,C). Detailed cortical features were better resolved with the new template compared to MCALT_0.5mm (Fig. 3A,B). Visual inspection revealed atypical anatomical structures in the cortex of MCALT_0.5mm (red circles) (Fig. 3B), absent in other templates. Inter‐subject spatial normalization accuracy was higher when using the new template compared to the other templates (Fig. 4A,B,C). The new template required lower deformation for spatially normalizing ADNI3 dataset (Fig. 5).

Conclusion

The new template is an unbiased high‐resolution detail‐preserving structural template of the older adult brain that requires lower deformation and provides higher spatial normalization accuracy for older adult data than other templates.