Journal of Alzheimer's Disease - Volume 91, issue 3

Authors: Perry, George

Article Type: Obituary

DOI: 10.3233/JAD-239000

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 913-913, 2023

Authors: Jia, Jianping | Zhang, Yue | Shi, Yuqing | Yin, Xuping | Wang, Shiyuan | Li, Yan | Zhao, Tan | Liu, Wenying | Zhou, Aihong | Jia, Longfei

Article Type: Short Communication

Abstract: Alzheimer’s disease (AD) primarily affects older adults. In this report, we present the case of a 19-year-old male with gradual memory decline for 2 years and World Health Organization-University of California Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) results also showing memory impairment. Positron emission tomography-magnetic resonance imaging with 18 F fluorodeoxyglucose revealed atrophy of the bilateral hippocampus and hypometabolism in the bilateral temporal lobe. Examination of the patient’s cerebrospinal fluid showed an increased concentration of p-tau181 and a decreased amyloid-β 42/40 ratio. However, through whole-genome sequencing, no known gene mutations were identified. Considering the above, the patient was …diagnosed with probable AD. Show more

Keywords: Case report, early-onset Alzheimer’s disease, gene mutation, hippocampal atrophy, memory impairment

DOI: 10.3233/JAD-221065

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 915-922, 2023

Authors: Perry, George

Article Type: Editorial

DOI: 10.3233/JAD-230016

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 923-924, 2023

Authors: Zhào, Hóngyi | Wei, Wei | Xie, Hongyang | Huang, Yonghua

Article Type: Short Communication

Abstract: Brain aging is characterized by the declines in motor and cognitive features. The present study is to detect motor cognitive risk syndrome (MCRS) in older adults with white matter lesions (WML). 134 WML aged patients were recruited and diagnosed with the criteria for MCRS. Numerous cognitive function tests and walking tests were performed. The frequency of MCRS is 28.35%. Verbal fluency test, Mini-Mental State Examination, and dual-task walking speed were independent risk factor of MCRS. These findings indicated that MCRS was common in WML seniors. MCRS was associated with the pathologies of WML in older adults.

Keywords: Aging, cerebral small vessel disease, dual-task walking, magnetic resonance imaging, motoric cognitive risk syndrome, white matter lesions

DOI: 10.3233/JAD-220712

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 925-931, 2023

Authors: Reeve, Emily | Chenoweth, Lynn | Sawan, Mouna | Nguyen, Tuan Anh | Kalisch Ellett, Lisa | Gilmartin-Thomas, Julia | Tan, Edwin | Sluggett, Janet K. | Quirke, Lyntara S. | Tran, Kham | Ailabouni, Nagham | Cowan, Katherine | Sinclair, Ron | de la Perrelle, Lenore | Deimel, Judy | To, Josephine | Daly, Stephanie | Whitehead, Craig | Hilmer, Sarah N.

Article Type: Research Article

Abstract: Background: Historically, research questions have been posed by the pharmaceutical industry or researchers, with little involvement of consumers and healthcare professionals. Objective: To determine what questions about medicine use are important to people living with dementia and their care team and whether they have been previously answered by research. Methods: The James Lind Alliance Priority Setting Partnership process was followed. A national Australian qualitative survey on medicine use in people living with dementia was conducted with consumers (people living with dementia and their carers including family, and friends) and healthcare professionals. Survey findings were supplemented with …key informant interviews and relevant published documents (identified by the research team). Conventional content analysis was used to generate summary questions. Finally, evidence checking was conducted to determine if the summary questions were ‘unanswered’. Results: A total of 545 questions were submitted by 228 survey participants (151 consumers and 77 healthcare professionals). Eight interviews were conducted with key informants and four relevant published documents were identified and reviewed. Overall, analysis resulted in 68 research questions, grouped into 13 themes. Themes with the greatest number of questions were related to co-morbidities, adverse drug reactions, treatment of dementia, and polypharmacy. Evidence checking resulted in 67 unanswered questions. Conclusion: A wide variety of unanswered research questions were identified. Addressing unanswered research questions identified by consumers and healthcare professionals through this process will ensure that areas of priority are targeted in future research to achieve optimal health outcomes through quality use of medicines. Show more

Keywords: Caregivers, clinical decision-making, dementia, deprescription, health services research, multiple chronic conditions, pharmacy research, polypharmacy

DOI: 10.3233/JAD-220827

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 933-960, 2023

Authors: Glover, Crystal M. | Arfanakis, Konstantinos | Aggarwal, Neelum T. | Bennett, David A. | Marquez, David X. | Barnes, Lisa L.

Article Type: Research Article

Abstract: Background: Biological biomarkers yielded from positron emission tomography (PET) brain scans serve as a pathway to understanding Alzheimer’s disease pathology. PET brain scan data remain limited for populations traditionally under-included in aging research. Objective: The purpose of this qualitative study was to examine participant-identified barriers to PET brain scan consent and characterize participant-informed elements of educational materials needed to facilitate PET brain scan participation among older Black and Latino adults. Methods: Participants (N = 31) were older adults (mean age = 71 years) who self-identified as either non-Latino Black (n  = 15) or Latino (n  = 16). Each participant took part in …a one-time, in-depth individual interview. Researchers analyzed data guided by a Grounded Theory Approach with both Open Coding and Constant Comparative Coding. Results: Four overarching themes emerged across all participants: 1) knowledge limitations; 2) requirements for consent; 3) motivators for participation; and 4) social networks. Within the four themes, there were differences based on participant ethnoracial group. For example, for Theme Three, older Black adults indicated that they would expect compensation for PET brain scan participation. Conversely, older Latinos stated that they would appreciate, but not anticipate, a financial incentive. All participants stressed the importance of written educational materials with subsequent verbal discussions with studystaff. Conclusion: Findings inform the development and implementation of scientifically-relevant and culturally-cognizant engagement approaches, educational materials, and recruitment strategies to increase PET brain scan participation by diverse older adults. Show more

Keywords: Older adults, PET brain scan, qualitative interviews, recruitment science, study design

DOI: 10.3233/JAD-220861

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 961-976, 2023

Authors: Li, Huiyue | Liu, Hongliang | Lutz, Michael W. | Luo, Sheng

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a common neurodegenerative disease and mild cognitive impairment (MCI) is considered as the prodromal stage of AD. Previous studies showed that changes in the neurotrophin signaling pathway could lead to cognitive decline in AD. However, the association of single nucleotide polymorphisms (SNPs) in genes that are involved in this pathway with AD progression from MCI remains unclear. Objective: We investigated the associations between SNPs involved in the neurotrophin signaling pathway with AD progression. Methods: We performed single-locus analysis to identify neurotrophin-signaling-related SNPs associated with the AD progression using 767 patients from …the Alzheimer’s Disease Neuroimaging Initiative study and 1,373 patients from the National Alzheimer’s Coordinating Center study. We constructed polygenic risk scores (PRSs) using the identified independent non-APOE SNPs and evaluated its prediction performance on AD progression. Results: We identified 25 SNPs significantly associated with AD progression with Bayesian false-discovery probability ≤0.8. Based on the linkage disequilibrium clumping and expression quantitative trait loci analysis, we found 6 potentially functional SNPs that were associated with AD progression independently. The PRS analysis quantified the combined effects of these SNPs on longitudinal cognitive assessments and biomarkers from cerebrospinal fluid and neuroimaging. The addition of PRSs to the prediction model for 3-year progression to AD from MCI significantly increased the predictive accuracy. Conclusion: Genetic variants in the specific genes of the neurotrophin signaling pathway are predictors of AD progression. eQTL analysis supports that these SNPs regulate expression of key genes involved in the neurotrophin signaling pathway. Show more

Keywords: Mild cognitive impairment, neurotrophins, single nucleotide polymorphism, survival analysis

DOI: 10.3233/JAD-220680

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 977-987, 2023

Authors: Chai, Yuek Ling | Liang, Nathan Hao Ping | Chong, Joyce R. | Venketasubramanian, Narayanaswamy | Tan, Boon Yeow | Hilal, Saima | Chen, Christopher P. | Lai, Mitchell K. P.

Article Type: Research Article

Abstract: Background: The lysosomal protease cathepsin D (catD) has been reported to be upregulated in postmortem Alzheimer’s disease (AD) cortex, where it colocalized with neurofibrillary tangles and correlated with levels of phosphorylated tau, suggesting pathophysiological links between catD and neurodegeneration. In contrast, studies of serum catD in AD have yielded conflicting results, and potential associations between baseline serum catD and functional outcomes of patients are at present unknown. Objective: We aimed to examine the status of serum catD in a Singapore-based longitudinal study of dementia and investigate catD associations with functional and cognitive decline. Methods: 35 subjects …with no cognitive impairment, 40 patients with cognitive impairment no dementia and 34 with AD dementia underwent annual neuropsychological assessments (mean follow-up=4.3 years), as well as collection of baseline serum for catD measurements by ELISA. Results: Higher serum catD at baseline was associated with AD clinical diagnosis (odds ratios [OR]: 10.0; 95% confidence interval [CI]: 1.02–97.95) as well as with cortical atrophy. Furthermore, higher catD was associated with global cognitive and functional decline (OR: 9.94; 95% CI: 1.02–97.34). Conclusion: The associations of serum catD with AD dementia as well as atrophy provide further support for the proposed links between catD and neurodegeneration, as well as for the assessment of serum catD as a prognostic biomarker predicting global cognitive and functional decline in larger studies. Show more

Keywords: Alzheimer’s disease, brain atrophy, cathepsin D, cognitive decline, lysosomal protease, neurodegeneration

DOI: 10.3233/JAD-220852

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 989-998, 2023

Authors: Meysami, Somayeh | Raji, Cyrus A. | Glatt, Ryan M. | Popa, Emily S. | Ganapathi, Aarthi S. | Bookheimer, Tess | Slyapich, Colby B. | Pierce, Kyron P. | Richards, Casey J. | Lampa, Melanie G. | Gill, Jaya M. | Rapozo, Molly K. | Hodes, John F. | Tongson, Ynez M. | Wong, Claudia L. | Kim, Mihae | Porter, Verna R. | Kaiser, Scott A. | Panos, Stella E. | Dye, Richelin V. | Miller, Karen J. | Bookheimer, Susan Y. | Martin, Neil A. | Kesari, Santosh | Kelly, Daniel F. | Bramen, Jennifer E. | Siddarth, Prabha | Merrill, David A.

Article Type: Research Article

Abstract: Background: Strength and mobility are essential for activities of daily living. With aging, weaker handgrip strength, mobility, and asymmetry predict poorer cognition. We therefore sought to quantify the relationship between handgrip metrics and volumes quantified on brain magnetic resonance imaging (MRI). Objective: To model the relationships between handgrip strength, mobility, and MRI volumetry. Methods: We selected 38 participants with Alzheimer’s disease dementia: biomarker evidence of amyloidosis and impaired cognition. Handgrip strength on dominant and non-dominant hands was measured with a hand dynamometer. Handgrip asymmetry was calculated. Two-minute walk test (2MWT) mobility evaluation was combined with handgrip …strength to identify non-frail versus frail persons. Brain MRI volumes were quantified with Neuroreader. Multiple regression adjusting for age, sex, education, handedness, body mass index, and head size modeled handgrip strength, asymmetry and 2MWT with brain volumes. We modeled non-frail versus frail status relationships with brain structures by analysis of covariance. Results: Higher non-dominant handgrip strength was associated with larger volumes in the hippocampus (p  = 0.02). Dominant handgrip strength was related to higher frontal lobe volumes (p  = 0.02). Higher 2MWT scores were associated with larger hippocampal (p  = 0.04), frontal (p  = 0.01), temporal (p  = 0.03), parietal (p  = 0.009), and occipital lobe (p  = 0.005) volumes. Frailty was associated with reduced frontal, temporal, and parietal lobe volumes. Conclusion: Greater handgrip strength and mobility were related to larger hippocampal and lobar brain volumes. Interventions focused on improving handgrip strength and mobility may seek to include quantified brain volumes on MR imaging as endpoints. Show more

Keywords: Brain volumes, handgrip, mobility, prevention

DOI: 10.3233/JAD-220886

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 999-1006, 2023

Authors: Chen, Qianyun | Abrigo, Jill | Deng, Min | Shi, Lin | Wang, Yi-Xiang | Chu, Winnie Chiu Wing

Article Type: Research Article

Abstract: Background: Diagnosis of Alzheimer’s disease (AD) was recently shifted from clinical to biological construct to reflect underlying neuropathological status, where amyloid deposition designated patients to the Alzheimer’s continuum, and additional tau positivity represented AD. Objective: To investigate white matter (WM) alteration in the brain of patients in the Alzheimer’s continuum. Methods: A total of 236 subjects across the clinical and biological spectra of AD were included and stratified by normal/abnormal (–/+) amyloid (A) and tau (T) status based on positron emission tomography results, yielding five groups: A–T–cognitively normal (CN), A+T–CN, A+T+ CN, A+T+ mild cognitive impairment, …and A+T+ AD. WM alteration was measured by diffusion tensor imaging (DTI). Group differences, correlation of DTI measures with amyloid and tau, and diagnostic performance of such measures were evaluated. Results: Compared with A–T–CN, widespread WM alteration was observed in the Alzheimer’s continuum, including hippocampal cingulum (CGH), cingulum of the cingulate gyrus, and uncinate fasciculus. Diffusion changes measured by regional mean fractional anisotropy (FA) in the bilateral CGH were first detected in the A+T+ CN group and associated with tau burden in the Alzheimer’s continuum (p  < 0.001). For discrimination between A+T+ CN and A–T–CN groups, CGH FA achieved accuracy, sensitivity, and specificity of 74%, 58%, and 78% for right CGH and 57%, 83%, and 47% respectively for left CGH. Conclusion: WM alteration is widespread in the Alzheimer’s continuum. Diffusion alteration in CGH occurred early and was correlated with tau pathology, thus may be a promising biomarker in preclinical AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, diffusion tensor imaging, hippocampal cingulum, tau

DOI: 10.3233/JAD-220671

Citation: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1007-1017, 2023