Journal of Alzheimer's Disease - Volume 100, issue 1

Authors: Huang, Lei | Ma, Jingxuan | Jiang, Fugui | Zhang, Shushan | Lan, Yajia | Zhang, Yang

Article Type: Research Article

Abstract: Background: Noise exposure and the risk of cognitive impairment are currently major public health issues. Objective: This study aimed to analyze the relationship between noise exposure and early impairment of cognitive function from the perspective of occupational epidemiology and to provide evidence for the long-term prevention and treatment of dementia in the context of aging. Methods: This study was conducted in China between May and August 2021. The independent variables were the type of hazardous factors, duration of noise exposure, perceived noise intensity, and cumulative noise exposure (CNE). The dependent variable was cognitive function, which was …measured using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Multiple linear and logistic regression were used to analyze the relationship between noise exposure and cognitive function and to establish an effect curve. Results: The detection rates of cognitive dysfunction using the MMSE and MoCA were 1.1% and 36.2%, respectively. The predicted MMSE and MoCA scores showed a downward trend within the CNE value ranging from 90–140 dB.time. Each unit increase in CNE decreased cognitive function scores by 0.025 (0.037, 0.013) and 0.020 (0.037, 0.003) points,respectively. Conclusions: From the perspective of occupational epidemiology, these findings reveal a potential link between long-term noise exposure and early cognitive impairment. Show more

Keywords: Alzheimer’s disease, cognitive impairment, cumulative dose, noise, occupational exposure

DOI: 10.3233/JAD-240061

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 151-161, 2024

Authors: Gibbons, Laura E. | Mobley, Taylor | Mayeda, Elizabeth Rose | Lee, Cecilia S. | Gatto, Nicole M. | LaCroix, Andrea Z. | McEvoy, Linda K. | Crane, Paul K. | Hayes-Larson, Eleanor

Article Type: Research Article

Abstract: Background: The Adult Changes in Thought (ACT) study is a cohort of Kaiser Permanente Washington members ages 65+ that began in 1994. Objective: We wanted to know how well ACT participants represented all older adults in the region, and how well ACT findings on eye disease and its relationship with Alzheimer’s disease generalized to all older adults in the Seattle Metropolitan Region. Methods: We used participation weights derived from pooling ACT and Behavioral Risk Factor Surveillance System (BRFSS) data to estimate prevalences of common eye diseases and their associations with Alzheimer’s disease incidence. Cox proportional hazards …models accounted for age, education, smoking, sex, and APOE genotype. Confidence intervals for weighted analyses were bootstrapped to account for error in estimating the weights. Results: ACT participants were fairly similar to older adults in the region. The largest differences were more self-reported current cholesterol medication use in BRFSS and higher proportions with low education in ACT. Incorporating the weights had little impact on prevalence estimates for age-related macular degeneration or glaucoma. Weighted estimates were slightly higher for diabetic retinopathy (weighted 5.7% (95% Confidence Interval 4.3, 7.1); unweighted 4.1% (3.6, 4.6)) and cataract history (weighted 51.8% (49.6, 54.3); unweighted 48.6% (47.3, 49.9)). The weighted hazard ratio for recent diabetic retinopathy diagnosis and Alzheimer’s disease was 1.84 (0.34, 4.29), versus 1.32 (0.87, 2.00) in unweighted ACT. Conclusions: Most, but not all, associations were similar after participation weighting. Even in community-based cohorts, extending inferences to broader populations may benefit from evaluation with participation weights. Show more

Keywords: Alzheimer’s disease, bias, dementia, epidemiological research design, eye diseases, generalizability, integrated health-care delivery systems, prevalence, transportability

DOI: 10.3233/JAD-240247

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 163-174, 2024

Authors: Cheng, Chia-Hsiung | Hsieh, Yu-Wei | Chang, Chiung-Chih | Hsiao, Fu-Jung | Chen, Li-Fen | Wang, Pei-Ning

Article Type: Research Article

Abstract: Background: Multidomain intervention may delay or ameliorate cognitive decline in older adults at risk of Alzheimer’s disease, particularly in the memory and inhibitory functions. However, no study systematically investigates the changes of brain function in cognitively-normal elderly with subjective cognitive decline (SCD) when they receive multidomain intervention. Objective: We aimed to examine whether a multidomain intervention could improve neuropsychological function and neurophysiological activities related to memory and inhibitory function in SCD subjects. Methods: Eight clusters with a total of 50 community-dwelling SCD older adults were single-blind, randomized into intervention group, which received physical and cognitive training, …or control group, which received treatment as usual. For the neuropsychological function, a composite Z score from six cognitive tests was calculated and compared between two groups. For the neurophysiological activities, event-related potentials (ERPs) of memory function, including mismatch negativity (MMN) and memory-P3, as well as ERPs of inhibitory function, including sensory gating (SG) and inhibition-P3, were measured. Assessments were performed at baseline (T1), end of the intervention (T2), and 6 months after T2 (T3). Results: For the neuropsychological function, the effect was not observed after the intervention. For the neurophysiological activities, improved MMN responses of ΔT2–T1 were observed in the intervention group versus the control group. The multidomain intervention produced a sustained effect on memory-P3 latencies of ΔT3–T1. However, there were no significant differences in changes of SG and inhibition-P3 between intervention and control groups. Conclusions: While not impactful on neuropsychological function, multidomain intervention enhances specific neurophysiological activities associated with memory function. Show more

Keywords: Alzheimer’s disease, event-related potential, lifestyle intervention, mismatch negativity, multidomain intervention, occupational therapy, P3

DOI: 10.3233/JAD-231257

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 175-192, 2024

Authors: Sannemann, Lena | Bartels, Claudia | Brosseron, Frederic | Buerger, Katharina | Fliessbach, Klaus | Freiesleben, Silka Dawn | Frommann, Ingo | Glanz, Wenzel | Heneka, Michael T. | Janowitz, Daniel | Kilimann, Ingo | Kleineidam, Luca | Lammerding, Dominik | Laske, Christoph | Munk, Matthias H.J. | Perneczky, Robert | Peters, Oliver | Priller, Josef | Rauchmann, Boris-Stephan | Rostamzadeh, Ayda | Roy-Kluth, Nina | Schild, Ann-Katrin | Schneider, Anja | Schneider, Luisa-Sophie | Spottke, Annika | Spruth, Eike Jakob | Teipel, Stefan | Wagner, Michael | Wiltfang, Jens | Wolfsgruber, Steffen | Duezel, Emrah | Jessen, Frank

Article Type: Research Article

Abstract: Background: The NIA-AA Research Framework on Alzheimer’s disease (AD) proposes a transitional stage (stage 2) characterized by subtle cognitive decline, subjective cognitive decline (SCD) and mild neurobehavioral symptoms (NPS). Objective: To identify participant clusters based on stage 2 features and assess their association with amyloid positivity in cognitively unimpaired individuals. Methods: We included baseline data of N  = 338 cognitively unimpaired participants from the DELCODE cohort with data on cerebrospinal fluid biomarkers for AD. Classification into the AD continuum (i.e., amyloid positivity, A+) was based on Aβ42/40 status. Neuropsychological test data were used to assess subtle …objective cognitive dysfunction (OBJ), the subjective cognitive decline interview (SCD-I) was used to detect SCD, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPS. A two-step cluster analysis was carried out and differences in AD biomarkers between clusters were analyzed. Results: We identified three distinct participant clusters based on presented symptoms. The highest rate of A+ participants (47.6%) was found in a cluster characterized by both OBJ and SCD. A cluster of participants that presented with SCD and NPS (A+:26.6%) and a cluster of participants with overall few symptoms (A+:19.7%) showed amyloid positivity in a range that was not higher than the expected A+ rate for the age group. Across the full sample, participants with a combination of SCD and OBJ in the memory domain showed a lower Aβ42 /ptau181 ratio compared to those with neither SCD nor OBJ. Conclusions: The cluster characterized by participants with OBJ and concomitant SCD was enriched for amyloid pathology. Show more

Keywords: Alzheimer’s disease, Alzheimer’s disease continuum, amyloid, cerebrospinal fluid biomarkers, NIA-AA stage 2, neuropsychiatric symptoms, preclinical Alzheimer’s disease, subjective cognitive decline

DOI: 10.3233/JAD-231335

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 193-205, 2024

Authors: Sun, Cheng-Kun | Guo, Fan | Ou, Ya-Nan | Zhang, Ming-Zhan | Tan, Lan | Tan, Meng-Shan

Article Type: Research Article

Abstract: Background: The association between carotid plaque and cognitive decline has recently been reported. However, the current research evidence is insufficient, and the possible causes of cognitive changes are unknown. Objective: This study aims to explore the relationships between carotid plaque and cognition functions, cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers in cognitively intact adults, and try to study the underlying mechanisms. Methods: We enrolled 165 cognitively normal participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study, who had CSF AD biomarker measurements and carotid ultrasound. Linear modeling was used to assess the association of carotid …plaque with CSF biomarkers and cognition. Additionally, mediation analysis was conducted through 10,000 bootstrapped iterations to explore potential links between carotid plaque, AD pathology, and cognition. Results: We found that carotid plaque exhibited significant correlations with Aβ42 (β = –1.173, p  = 0.022), Aβ42 /Aβ40 (β = –0.092, p  < 0.001), P-tau/Aβ42 (β = 0.110, p  = 0.045), and T-tau/Aβ42 (β = 0.451, p  = 0.010). A significant correlation between carotid plaque and cognition decline was also found in men (β = –0.129, p  = 0.021), and mediation analyses revealed that the effect of carotid plaque on cognitive function could be mediated by Aβ42 /Aβ40 (proportion of mediation = 55.8%), P-tau/Aβ42 (proportion of mediation = 51.6%, p  = 0.015) and T-tau/Aβ42 (proportion of mediation = 43.8%, p  = 0.015) mediated. Conclusions: This study demonstrated the link between carotid plaque and CSF AD biomarkers in cognitively intact adults, and the important role that AD pathology may play in the correlation between carotid plaque and cognitive changes. Show more

Keywords: Alzheimer’s disease, biomarkers, carotid plaque, cognitive function, pathogenesis

DOI: 10.3233/JAD-240131

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 207-217, 2024

Authors: Fukui, Yusuke | Tadokoro, Koh | Hamada, Minaki | Asada, Kyoichi | Lee, Lyang-Ja | Tachiki, Hidehisa | Morihara, Ryuta | Abe, Koji | Yamashita, Toru

Article Type: Research Article

Abstract: Background: With the aging of populations worldwide, Alzheimer’s disease (AD) has become a concern due to its high prevalence and the continued lack of established treatments. Early diagnosis is required as a preventive intervention to modify the disease’s progression. In our previous study, we performed peptidomic analysis of serum samples obtained from AD patients and age-matched healthy subjects to seek peptide biomarker candidates for AD by using BLOTCHIP-MS analysis, and identified four peptides as AD biomarker candidates. Objective: The objective was to validate the serum biomarker peptides to distinguish mild cognitive impairment (MCI) and AD in comparison to …cognitively healthy controls using a new peptidome technology, the Dementia Risk Test. Methods: We enrolled 195 subjects with normal cognitive function (NC; n  = 70), MCI (n  = 55), and AD (n  = 70), The concentrations of cognitive impairment marker peptides (Fibrinogen α chain (FAC), Fibrinogen β chain (FBC), Plasma protease C1 inhibitor (PPC1I), α 2-HS-glycoprotein (AHSG)) were quantified by using a selected reaction monitoring assay based on liquid chromatography-MS/MS. Results: The present study confirmed that three peptides, FAC, FBC, and PPC1I, were significantly upregulated during the onset of AD. This three-peptide set was both highly sensitive in determining AD (sensitivity: 85.7%, specificity: 95.7%, AUC: 0.900) and useful in distinguishing MCI (sensitivity: 61.8%, specificity: 98.6%, AUC: 0.824) from NC. Conclusions: In this validation study, we confirmed the high diagnostic potential of the three peptides identified in our previous study as candidate serum biomarkers for AD. The Dementia Risk Test may be a powerful tool for detecting AD-related pathological changes. Show more

Keywords: Alzheimer’s disease, biochemical marker, dementia risk test, liquid chromatography-MS/MS, mild cognitive impairment, peptidome, selected reaction monitoring

DOI: 10.3233/JAD-230915

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 219-228, 2024

Authors: Ning, Min | An, Lina | Dong, Liang | Zhu, Ranran | Hao, Jingjing | Liu, Xueyuan | Zhang, Yuanyuan

Article Type: Research Article

Abstract: Background: Multiple studies have demonstrated that the gut microbiome is closely related to the onset of Alzheimer’s disease, but the causal relationship between the gut microbiome and AD, as well as potential mediating factors, have not been fully explored. Objective: Our aim is to validate the causal relationship between the gut microbiome and the onset of AD and determine the key mechanism by which the gut microbiome mediates AD through blood metabolites using Mendelian randomization (MR) analysis methods. Methods: We first conducted bidirectional and mediating MR analyses using gut microbiota, blood amino acid metabolites, and AD-related …single nucleotide polymorphisms as research data. In the analysis process, the inverse variance-weighted average method was mainly used as the primary method, with other methods serving as supplementary evidence. Results: Ultimately, we found that six types of gut bacteria and two blood amino acid metabolites have a causal effect on AD. Subsequent mediation analysis proved that decreased glutamine concentration mediates the negative causal effect of Holdemanella bacteria on AD (mediation ratio of 14.5%), and increased serum alanine concentration mediates the positive causal effect of Parabacteroide bacteria on AD (mediation ratio of 9.4%). Conclusions: Our study demonstrates the causality of Holdemanella and Parabacteroides bacteria in the onset of AD and suggests that the reduced glutamine and increased alanine serums concentration may be key nodes in mediating this effect. Show more

Keywords: Alzheimer’s disease, gut microbiome, Mendelian randomization, metabolites

DOI: 10.3233/JAD-240082

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 229-237, 2024

Authors: Patel, Hemal | Wisely, C. Ellis | Robbins, Cason B. | Parker, Daniel | Challa, Pratap | Grewal, Dilraj S. | Fekrat, Sharon

Article Type: Research Article

Abstract: Background: Plasma and cerebrospinal fluid (CSF) levels of p-tau181 have been associated with Alzheimer’s disease (AD). The retina and vitreous have shown measurable quantities of phosphorylated tau 181 (p-tau181). The aqueous humor, which can be collected during cataract surgery, may have measurable concentrations of p-tau181. Objective: To determine whether p-tau181 is detectable in the aqueous humor and if so, whether it is associated with other measures that might be consistent with AD such as higher plasma p-tau181 concentration and lower Montreal Cognitive Assessment (MoCA-BLIND version 7.1) score. Methods: Aqueous humor samples, blood samples, and MoCA-BLIND scores …were collected from patients who did not carry a clinical diagnosis of cognitive impairment at the time of cataract surgery. Aqueous p-tau181 concentrations and plasma p-tau181 concentrations were then measured using ultra-sensitive single-molecule assay ELISA technology. A rank-transformed mixed-effects multivariate regression model was used to determine associations between aqueous concentrations, plasma concentrations, and MoCA-BLIND scores. Results: 16 eyes of 16 participants were enrolled with an average age of 71.6. Average MoCA-BLIND score was 20.6/22, average aqueous p-tau181 concentration was 6.4 pg/mL, and average plasma p-tau181 concentration was 3.1 pg/mL. Higher plasma p-tau181 was significantly associated with higher aqueous p-tau181 (p  = 0.02). Aqueous p-tau181 and plasma p-tau181 were negatively associated with MoCA-BLIND scores (p  = 0.005 and p  = 0.001 respectively) in these patients. Conclusions: Aqueous p-tau181 is positively correlated with plasma p-tau181 and is negatively correlated with MoCA-BLIND scores. Further study in individuals with mild cognitive impairment or AD characterized by cerebrospinal fluid and volumetric MRI metrics may yield further insights. Show more

Keywords: Alzheimer’s disease, aqueous humor, enzyme-linked immunosorbent assay, tau proteins

DOI: 10.3233/JAD-240279

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 239-245, 2024

Authors: Kemiläinen, Benjam | Tiainen, Sonja | Rauramaa, Tuomas | Luikku, Antti J. | Herukka, Sanna-Kaisa | Koivisto, Anne | Hiltunen, Mikko | Verdooner, Steven | Johnson, Ken | Chambers, Mieko | Kaarniranta, Kai | Leinonen, Ville

Article Type: Research Article

Abstract: Background: Association between visual field test indices and The Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-NB) is unknown. Idiopathic normal pressure hydrocephalus (iNPH) patients provide a unique set of patient data for analysis. Objective: To assess the reliability of visual field testing using the CERAD-NB in patients with iNPH and to investigate the association between visual field test results and cognitive function. Methods: 62 probable iNPH patients were subjected to comprehensive ophthalmological examination, ophthalmological optical coherence tomography imaging studies, visual field testing, and CERAD-NB. Based on visual field indices, the patients were …divided into two groups: unreliable (n  = 19) and reliable (n  = 43). Independent T-test analysis was performed to examine the relationship between visual field test results and cognitive function. Pearson Chi-square test was used for non-continuous variables. Results: The unreliable group performed worse in CERAD-NB subtests compared to the reliable group. Statistically significant differences were observed in nine out of ten subtests, with only Clock Drawing showing no statistical significance. Pairwise comparison of the groups showed no statistical significance between amyloid-β (Aβ) biopsy, hyperphosphorylated tau biopsy, apolipoprotein E allele or the ophthalmological status of the patient. But there was a statistically significant difference in cerebrospinal fluid Aβ42 and age between the groups. Conclusions: Patients with unreliable visual field tests performed worse on CERAD-NB subtests. CERAD-NB subtests do not provide a specific cut-off value to refrain patients from visual field testing. Should patients with unreliable visual field tests be screened for cognitive impairment? Show more

Keywords: Alzheimer’s disease, amyloid-β , APOE , CERAD-NB, cognitive impairment, normal pressure hydrocephalus, optical coherence tomography, visual field tests

DOI: 10.3233/JAD-231414

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 247-260, 2024

Authors: Li, Dazhi | Xie, Qiang | Xie, Jikui | Ni, Ming | Wang, Jinliang | Gao, Yuru | Wang, Yaxin | Tang, Qiqiang

Article Type: Research Article

Abstract: Background: Early-onset Alzheimer’s disease (EOAD) exhibits a notable degree of heterogeneity as compared to late-onset Alzheimer’s disease (LOAD). The proteins and pathways contributing to the pathophysiology of EOAD still need to be completed and elucidated. Objective: Using correlation network analysis and machine learning to analyze cerebrospinal fluid (CSF) proteomics data to identify potential biomarkers and pathways associated with EOAD. Methods: We employed mass spectrometry to conduct CSF proteomic analysis using the data-independent acquisition method in a Chinese cohort of 139 CSF samples, including 40 individuals with normal cognition (CN), 61 patients with EOAD, and 38 patients …with LOAD. Correlation network analysis of differentially expressed proteins was performed to identify EOAD-associated pathways. Machine learning assisted in identifying crucial proteins differentiating EOAD. We validated the results in an Western cohort and examined the proteins expression by enzyme-linked immunosorbent assay (ELISA) in additional 9 EOAD, 9 LOAD, and 9 CN samples from our cohort. Results: We quantified 2,168 CSF proteins. Following adjustment for age and sex, EOAD exhibited a significantly greater number of differentially expressed proteins than LOAD compared to CN. Additionally, our data indicates that EOAD may exhibit more pronounced synaptic dysfunction than LOAD. Three potential biomarkers for EOAD were identified: SH3BGRL3, LRP8, and LY6 H, of which SH3BGRL3 also accurately classified EOAD in the Western cohort. LY6 H reduction was confirmed via ELISA, which was consistent with our proteomic results Conclusions: This study provides a comprehensive profile of the CSF proteome in EOAD and identifies three potential EOAD biomarker proteins. Show more

Keywords: Alzheimer’s disease, early-onset Alzheimer’s disease, biomarker, cerebrospinal fluid, machine learning, proteomics

DOI: 10.3233/JAD-240022

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 261-277, 2024

Authors: Liang, Xiao | Wang, Yangyang | Li, Siyu | Fan, Jianing | Zhou, Fanlin | Li, Xiaoju | Li, Shijie | Li, Yu

Article Type: Research Article

Abstract: Background: Mitochondrial dysfunction exists in Alzheimer’s disease (AD) brain, and damaged mitochondria need to be removed by mitophagy. Small GTPase Rab7 regulates the fusion of mitochondria and lysosome, while TBC1D5 inhibits Rab7 activation. However, it is not clear whether the regulation of Rab7 activity by TBC1D5 can improve mitophagy and inhibit AD progression. Objective: To investigate the role of TBC1D5 in mitophagy and its regulatory mechanism for Rab7, and whether activation of mitophagy can inhibit the progression of AD. Methods: Mitophagy was determined by western blot and immunofluorescence. The morphology and quantity of mitochondria were tracked …by TEM. pCMV-Mito-AT1.03 was employed to detect the cellular ATP. Amyloid-β secreted by AD cells was detected by ELISA. Co-immunoprecipitation was used to investigate the binding partner of the target protein. Golgi-cox staining was applied to observe neuronal morphology of mice. The Morris water maze test and Y-maze were performed to assess spatial learning and memory, and the open field test was measured to evaluate motor function and anxiety-like phenotype of experimental animals. Results: Mitochondrial morphology was impaired in AD models, and TBC1D5 was highly expressed. Knocking down TBC1D5 increased the expression of active Rab7, promoted the fusion of lysosome and autophagosome, thus improving mitophagy, and improved the morphology of hippocampal neurons and the impaired behavior in AD mice. Conclusions: Knocking down TBC1D5 increased Rab7 activity and promoted the fusion of autophagosome and lysosome. Our study provided insights into the mechanisms that bring new possibilities for AD therapy targeting mitophagy. Show more

Keywords: Alzheimer’s disease, mitophagy, Rab7, TBC1D5

DOI: 10.3233/JAD-231300

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 279-296, 2024

Authors: Shrestha, Srishti | Zhu, Xiaoqian | Sullivan, Kevin J. | Simino, Jeannette | Lutsey, Pamela L. | Gottesman, Rebecca F. | London, Stephanie J. | Griswold, Michael E. | Mosley, Jr., Thomas H.

Article Type: Research Article

Abstract: Background: Brain imaging studies may provide etiologic insight into observed links between lung function and dementia and stroke. Objective: We evaluated associations of lung function measures with brain MRI markers of vascular and neurodegenerative disease in the ARIC Neurocognitive Study, as few studies have examined the associations. Methods: Lung function was measured at participants’ midlife in 1990–1992 (mean age = 56±5 years) and later-life in 2011–2013 (mean age = 76±5 years), and brain MRI was performed in 2011–2013. Linear regression models were used to examine the associations of lung function with brain and white matter hyperintensity (WMH) volumes, and logistic …regression models were used for cerebral infarcts and microbleeds, adjusting for potential confounders. Results: In cross-sectional analysis (i.e., examining later-life lung function and MRI markers, n  = 1,223), higher forced-expiratory volume in one second (FEV1 ) and forced vital capacity (FVC) were associated with larger brain and lower WMH volumes [e.g., 8.62 (95% CI:2.54–14.71) cm3 greater total brain volume per one-liter higher FEV1 ]. No association was seen with microbleeds in the overall sample, but higher FVC was associated with lower odds of microbleeds in never-smokers and higher odds in ever-smokers. In the cross-temporal analysis (i.e., associations with midlife lung function, n  = 1,787), higher FVC levels were significantly associated with lower later-life brain volumes. Conclusions: Our results support modest associations of better lung function with less neurodegenerative and cerebrovascular pathology, although findings for microbleeds were unexpected in ever-smokers. Show more

Keywords: Alzheimer’s disease, brain volumes, cerebral infarct, lung function, white matter hyperintensity volume

DOI: 10.3233/JAD-240162

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 297-308, 2024

Authors: Lee, Cecilia S. | Ferguson, Alina N. | Gibbons, Laura E. | Walker, Rod | Su, Yu-Ru | Krakauer, Chloe | Brush, Michael | Kam, Jason | Larson, Eric B. | Arterburn, David E. | Crane, Paul K. | Takahashi, Missy | Zhang, Yi | Jiang, Yu | Wu, Yue | Cooper, Julie | Pope, Beth | Blazes, Marian | Lee, Aaron Y. | Lee, Michael L. | Wang, Ruikang | Cronkite, David | Hess, Chantelle | Bowers, Will | Schaaf, Beverly | Gray, Regan | Guerrero, Linda | Sankaran, Sundary | Gatto, Nicole

Article Type: Research Article

Abstract: Background: Conflicting research on retinal biomarkers of Alzheimer’s disease and related dementias (AD/ADRD) is likely related to limited sample sizes, study design, and protocol differences. Objective: The prospective Eye Adult Changes in Thought (Eye ACT) seeks to address these gaps. Methods: Eye ACT participants are recruited from ACT, an ongoing cohort of dementia-free, older adults followed biennially until AD/ADRD, and undergo visual function and retinal imaging assessment either in clinic or at home. Results: 330 participants were recruited as of 03/2023. Compared to ACT participants not in Eye ACT (N  = 1868), Eye ACT participants (N … = 330) are younger (mean age: 70.3 versus 71.2, p  = 0.014), newer to ACT (median ACT visits since baseline: 3 versus 4, p  < 0.001), have more years of education (17.7 versus 16.2, p  < 0.001) and had lower rates of visual impairment (12% versus 22%, p  < 0.001). Compared to those seen in clinic (N  = 300), Eye ACT participants seen at home (N  = 30) are older (77.2 versus 74.9, p  = 0.015), more frequently female (60% versus 49%, p  = 0.026), and have significantly worse visual acuity (71.1 versus 78.9 Early Treatment Diabetic Retinopathy Study letters, p  < 0.001) and contrast sensitivity (–1.9 versus –2.1 mean log units at 3 cycles per degree, p  = 0.002). Cognitive scores and retinal imaging measurements are similar between the two groups. Conclusions: Participants assessed at home had significantly worse visual function than those seen in clinic. By including these participants, Eye ACT provides a unique longitudinal cohort for evaluating potential retinal biomarkers of dementia. Show more

Keywords: Adult Changes in Thought (ACT), age-related macular degeneration, Alzheimer’s disease, Cognitive Abilities Screening Instrument (CASI) score, contrast sensitivity, Eye Adult Changes in Thought (Eye ACT), ophthalmology, optical coherence measurement, prospective study, visual acuity

DOI: 10.3233/JAD-240203

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 309-320, 2024

Authors: Chen, Yu-Han | Wang, Zhi-Bo | Liu, Xi-Peng | Mao, Zhi-Qi

Article Type: Research Article

Abstract: Background: Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer’s disease (AD), sharing similar pathophysiological traits like impaired insulin signaling. Objective: To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology. Methods: A total of 304 participants were included in the Alzheimer’s Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages. Results: In the non-demented group, amyloid-β (Aβ)+ participants (e.g., as …reflected by CSF Aβ42 ) exhibited significantly lower plasma insulin levels compared to non-demented Aβ–participants (p  < 0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF Aβ42 and pTau181 levels) when compared to the A–T– group within the non-dementia group (p  = 0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF Aβ42 levels (p  < 0.001) across all participants. This association was particularly significant in the Aβ–group (p  = 0.002) and among non-demented individuals (p  < 0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF Aβ42 (p  = 0.006), whereas baseline CSF Aβ42 did not show a similar correlation with changes in plasma insulin over time. Conclusions: These findings suggest an association between plasma insulin and early Aβ pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early Aβ pathology. Show more

Keywords: Alzheimer’s disease, amyloid, diabetes, plasma insulin, pTau

DOI: 10.3233/JAD-240289

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 321-332, 2024

Authors: Lalive, Hadrien M. | Griffa, Alessandra | Carlier, Sabrina | Nasuti, Mirco | Di Noto, Tommaso | Maréchal, Bénédicte | Rouaud, Olivier | Allali, Gilles

Article Type: Research Article

Abstract: Background: Amnestic syndrome of the hippocampal type (ASHT) in Memory Clinics is a presentation common to Alzheimer’s disease (AD). However, ASHT can be found in other neurodegenerative disorders. Objective: To compare brain morphometry including hippocampal volumes between amnestic older adults with and without AD pathology and investigate their relationship with memory performance and cerebrospinal fluid (CSF) biomarkers. Methods: Brain morphometry of 92 consecutive patients (72.5±6.8 years old; 39% female) with Free and Cued Selective Recall Reminding Test (FCSRT) total recall < 40/48 was assessed with an automated algorithm and compared between AD and non-AD patients, as defined by …CSF biomarkers. Results: AD and non-AD patients presented comparable brain morphology. Total recall was associated to hippocampal volume irrespectively from AD pathology. Conclusions: Brain morphometry, including hippocampal volumes, is similar between AD and non-AD older adults with ASHT evaluated in a Memory Clinic, underlying the importance of using molecular biomarkers for the diagnosis of AD. Show more

Keywords: Alzheimer’s disease, amnestic, hippocampus, magnetic resonance imaging

DOI: 10.3233/JAD-240026

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 333-343, 2024

Authors: Michalowsky, Bernhard | Rädke, Anika | Scharf, Annelie | Mühlichen, Franka | Buchholz, Maresa | Platen, Moritz | Kleinke, Fabian | Penndorf, Peter | Pfitzner, Stefanie | van den Berg, Neeltje | Hoffmann, Wolfgang

Article Type: Research Article

Abstract: Background: Determining unmet need patterns and associated factors in primary care can potentially specify assessment batteries and tailor interventions in dementia more efficiently. Objective: To identify latent unmet healthcare need patterns and associated sociodemographic and clinical factors. Methods: This Latent Class Analysis (LCA) includes n  = 417 community-dwelling people living with dementia. Subjects completed a comprehensive, computer-assisted face-to-face interview to identify unmet needs. One-hundred-fifteen predefined unmet medical, medication, nursing, psychosocial, and social care needs were available. LCA and multivariate logistic regressions were performed to identify unmet needs patterns and patient characteristics belonging to a specific pattern, respectively. …Results: Four profiles were identified: [1 ] “few needs without any psychosocial need” (n  = 44 (11%); mean: 7.4 needs), [2 ] “some medical and nursing care needs only” (n  = 135 (32%); 9.7 needs), [3 ] “some needs in all areas” (n  = 139 (33%); 14.3 needs), and [4 ] “many medical and nursing needs” (n  = 99 (24%); 19.1 needs). Whereas the first class with the lowest number of needs comprised younger, less cognitively impaired patients without depressive symptoms, the fourth class had the highest number of unmet needs, containing patients with lower health status, less social support and higher comorbidity and depressive symptoms. Better access to social care services and higher social support reduced unmet needs, distinguishing the second from the third class (9.7 versus 14.3 needs). Conclusions: Access to the social care system, social support and depressive symptoms should be assessed, and the patient’s health status and comorbidities monitored to more comprehensively identify unmet needs patterns and more efficiently guide tailored interventions. Show more

Keywords: Alzheimer’s disease, dementia, latent class analysis, primary care, profiles, unmet needs

DOI: 10.3233/JAD-240025

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 345-356, 2024

Authors: Lee, Ann J. | Stark, Jessica H. | Hayes, Scott M.

Article Type: Research Article

Abstract: Background: Executive dysfunction in mild cognitive impairment (MCI) has been associated with gray matter atrophy. Prior studies have yielded limited insight into associations between gray matter volume and executive function in early and late amnestic MCI (aMCI). Objective: To examine the relative importance of predictors of executive function at 24 months and relationships between baseline regional gray matter volume and executive function performance at 24-month follow-up in non-demented older adults. Methods: 147 participants from the Alzheimer’s Disease Neuroimaging Initiative (mean age = 70.6 years) completed brain magnetic resonance imaging and neuropsychological testing and were classified as cognitively normal …(n  = 49), early aMCI (n  = 60), or late aMCI (n  = 38). Analyses explored the importance of demographic, APOE ɛ 4, biomarker (p-tau/Aβ42 , t-tau/Aβ42 ), and gray matter regions-of-interest (ROI) variables to 24-month executive function, whether ROIs predicted executive function, and whether relationships varied by baseline diagnostic status. Results: Across all participants, baseline anterior cingulate cortex and superior parietal lobule volumes were the strongest predictors of 24-month executive function performance. In early aMCI, anterior cingulate cortex volume was the strongest predictor and demonstrated a significant interaction such that lower volume related to worse 24-month executive function in early aMCI. Educational attainment and inferior frontal gyrus volume were the strongest predictors of 24-month executive function performance for cognitively normal and late aMCI groups, respectively. Conclusions: Baseline frontoparietal gray matter regions were significant predictors of executive function performance in the context of aMCI and may identify those at risk of Alzheimer’s disease. Anterior cingulate cortex volume may predict executive function performance in early aMCI. Show more

Keywords: Aging, Alzheimer’s disease, anterior cingulate cortex, executive function, gray matter, magnetic resonance imaging, mild cognitive impairment

DOI: 10.3233/JAD-231468

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 357-374, 2024

Article Type: Correction

DOI: 10.3233/JAD-249010

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 375-375, 2024