Journal of Alzheimer's Disease - Volume 73, issue 2

Authors: Zuelsdorff, Megan | Okonkwo, Ozioma C. | Norton, Derek | Barnes, Lisa L. | Graham, Karen L. | Clark, Lindsay R. | Wyman, Mary F. | Benton, Susan F. | Gee, Alexander | Lambrou, Nickolas | Johnson, Sterling C. | Gleason, Carey E.

Article Type: Research Article

Abstract: Background: It is well-documented that African Americans have elevated risk for cognitive impairment and dementia in late life, but reasons for the racial disparities remain unknown. Stress processes have been linked to premature age-related morbidity, including Alzheimer’s and related dementias (ADRD), and plausibly contribute to social disparities in cognitive aging. Objective: We examined the relationship between stressful life events and cognitive decline among African American and White participants enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP). Methods: Linear mixed models including demographic, literacy, and health-related covariates were used to estimate (1) relationships between a life …event index score and decline in cognitive test performance in two domains of executive function (Speed & Flexibility, Working Memory) and one domain of episodic memory (Verbal Learning & Memory) among 1,241 WRAP enrollees, stratified by race, and (2) contributions of stressful life events to racial differences in cognition within the full sample. Results: African Americans (N = 50) reported more stressful life events than Whites (N = 1,191). Higher stress scores associated with poorer Speed & Flexibility performance in both groups, though not with declines across time, and partially explained racial differentials in this domain. Among African Americans only, stressor exposure also associated with age-related decline in Verbal Learning & Memory. Stressor-cognition relationships were independent of literacy and health-related variables. Conclusions: Greater lifetime stress predicted poorer later-life cognition, and, in a small sample of African Americans, faster declines in a key domain of episodic memory. These preliminary findings suggest that future work in large minority aging cohorts should explore stress as an important source of modifiable, socially-rooted risk for impairment and ADRD in African Americans, who are disproportionately exposed to adverse experiences across the life course. Show more

Keywords: African Americans, Alzheimer’s disease, life course, stress

DOI: 10.3233/JAD-190439

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 671-682, 2020

Authors: van Havre, Zoe | Maruff, Paul | Villemagne, Victor L. | Mengersen, Kerrie | Rousseau, Judith | White, Nicole | Doecke, James D.

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) has a long pathological process, with an approximate lead-time of 20 years. During the early stages of the disease process, little evidence of the building pathology is identifiable without cerebrospinal fluid and/or imaging analyses. Clinical manifestations of AD do not present until irreversible pathological changes have occurred. Given an opportunity to provide treatment prior to irreversible pathological change, this study aims to identify a subgroup of cognitively normal (CN) participants from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL), where subtle changes in cognition are indicative of early AD-related pathology. Using a Bayesian method …for unsupervised clustering via mixture models, we define an aggregate measure of posterior probabilities (AMPP score) establishing the likelihood of pre-clinical AD. From Baseline through to 54 months, visuo-spatial function had the greatest contribution to the AMPP score, followed by attention and processing speed and visual memory. Participants with the highest AMPP scores had both increasing neo-cortical amyloid burden and decreasing hippocampus volume over 54 months, compared to those in the lowest category with stable amyloid burden and hippocampus volume. The identification of a possible pre-clinical stage in CN participants via this method, without the aid of disease specific biomarkers, represents an important step in utilizing the strength of cognitive composite scores for the early detection of AD pathology. Show more

Keywords: Alzheimer’s disease, Bayesian, mixture models, model averaging, neuropsychological composite score, overfitting, posterior probability, unsupervised clustering

DOI: 10.3233/JAD-191095

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 683-693, 2020

Authors: Kumar, Rajnish | Pavlov, Pavel F. | Winblad, Bengt

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) represents a major public health threat and, unfortunately, available therapeutics provide only temporary symptomatic relief. AD is a complex multifactorial disease and failure of single target therapeutics targeting amyloid-β (Aβ) in recent clinical trials suggests that future AD drug development should be focused on simultaneous targeting of several pathological hallmarks of the disease. Recently, we have shown that GMP-1, a 2-(methoxymethyl)pyrimido [1, 2-a ] benzimidazol-4-ol, protects mitochondrial function in drosophila and mice models of AD, and improved memory and behavior indicating neuroprotective effect of GMP-1 treatment. Here, we have found that GMP-1 specifically binds to copper and zinc, …metals that are dysregulated in AD brain. Addition of GMP-1 does not inhibit metal-dependent enzymatic reactions. Also, binding of Zn(II) and Cu(II) by GMP-1 is weaker than the 8-hydroxyquinoline scaffold compound clioquinol previously tested in AD clinical trials. However, GMP-1 affects Cu(II)-dependent Aβ fibrillization as well as oxidative damage and viability of SH-SY5Y cells upon addition of Cu(II) and Aβ. Our data provide new insight on GMP-1 as a Zn(II) and Cu(II) specific metal chelator of moderate affinity that can be responsible for some of its neuroprotective effects observed in AD animal models. Show more

Keywords: Alzheimer’s disease, metal chelation, multi-target-directed ligands, treatment strategies

DOI: 10.3233/JAD-190695

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 695-705, 2020

Authors: Fani, Lana | Hilal, Saima | Sedaghat, Sanaz | Broer, Linda | Licher, Silvan | Arp, Pascal P. | van Meurs, Joyce B.J. | Ikram, M. Kamran | Ikram, M. Arfan

Article Type: Research Article

Abstract: There is a wide interest in biomarkers that capture the burden of detrimental factors as these accumulate with the passage of time, i.e., increasing age. Telomere length has received considerable attention as such a marker, because it is easily quantified and it may aid in disentangling the etiology of dementia or serve as predictive marker. We determined the association of telomere length with risk of Alzheimer’s disease and all-cause dementia in a population-based setting. Within the Rotterdam Study, we performed quantitative PCR to measure mean leukocyte telomere length in blood. We determined the association of telomere length with risk of …Alzheimer’s disease until 2016, using Cox regression models. Of 1,961 participants (mean age 71.4±9.3 years, 57.1% women) with a median follow-up of 8.3 years, 237 individuals were diagnosed with Alzheimer’s disease. We found a U-shaped association between telomere length and risk of Alzheimer’s disease: compared to the middle tertile the adjusted hazard ratio was 1.59 (95% confidence interval (CI), 1.13–2.23) for the lowest tertile and 1.47 (1.03–2.10) for the highest tertile. Results were similarly U-shaped but slightly attenuated for all-cause dementia. In conclusion, shorter and longer telomere length are both associated with an increased risk of Alzheimer’s disease in the general population. Show more

Keywords: Alzheimer’s disease, dementia, population-based, prospective cohort study, telomere

DOI: 10.3233/JAD-190759

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 707-714, 2020

Authors: Canevelli, Marco | Zaccaria, Valerio | Lacorte, Eleonora | Cova, Ilaria | Remoli, Giulia | Bacigalupo, Ilaria | Cascini, Silvia | Bargagli, Anna Maria | Pomati, Simone | Pantoni, Leonardo | Vanacore, Nicola

Article Type: Research Article

Abstract: Background: The construct of mild cognitive impairment (MCI) is triggering growing clinical and research interest. The detection of MCI may be affected by diverse ethno-cultural determinants possibly influencing the personal and social perception of the individual cognitive functioning as well as the reliability of objective cognitive assessment. These challenges may acquire special relevance in subjects with a migration background and composing ethnic minority groups. Objective: The present study is aimed at providing an estimate of the number of MCI cases occurring in the migrant population living in the extended European Union (EU) in 2018. Methods: The …number of MCI cases in older migrants living in Europe and in each of the 32 considered countries was estimated by multiplying the number of migrants, provided by Eurostat, with the age-specific prevalence rates, derived by the harmonized data produced by the COSMIC collaboration and based on different operational definitions of MCI. Results: Nearly 686,000 cases of MCI were estimated in the extended EU by applying age-specific prevalence rates based on the International Working Group criteria. Higher figures were obtained when the Clinical Dementia Rating- and the Mini Mental State Examination-based criteria were applied. The proportion of MCI cases in migrant subjects ranged from 1.1% (Romania) to 54.1% (Liechtenstein) (median: 8.4%; IQR: 4.7%–14.2%). Conclusions: MCI represents and will increasingly constitute a relevant issue in the migrant population living in Europe. The present data reinforce the need of developing approaches and models of care that may be diversity-sensitive and inclusive for a culturally variegated population. Show more

Keywords: Cognitive disorders, health disparities, migration, mild cognitive impairment, neuroepidemiology

DOI: 10.3233/JAD-191012

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 715-721, 2020

Authors: Wilson, Edward N. | Do Carmo, Sonia | Welikovitch, Lindsay A. | Hall, Hélène | Aguilar, Lisi Flores | Foret, Morgan K. | Iulita, M. Florencia | Jia, Dan Tong | Marks, Adam R. | Allard, Simon | Emmerson, Joshua T. | Ducatenzeiler, Adriana | Cuello, A. Claudio

Article Type: Research Article

Abstract: Epidemiological, preclinical, and clinical studies have suggested a role for microdose lithium in reducing Alzheimer’s disease (AD) risk by modulating key mechanisms associated with AD pathology. The novel microdose lithium formulation, NP03, has disease-modifying effects in the McGill-R-Thy1-APP transgenic rat model of AD-like amyloidosis at pre-plaque stages, before frank amyloid-β (Aβ) plaque deposition, during which Aβ is primarily intraneuronal. Here, we are interested in determining whether the positive effects of microdose lithium extend into early Aβ post-plaque stages. We administered NP03 (40μ g Li/kg; 1 ml/kg body weight) to McGill-R-Thy1-APP transgenic rats for 12 weeks spanning the transition phase from …plaque-free to plaque-bearing. The effect of NP03 on remote working memory was assessed using the novel object recognition task. Levels of human Aβ38 , Aβ40 , and Aβ42 as well as levels of pro-inflammatory mediators were measured in brain-extracts and plasma using electrochemiluminescent assays. Mature Aβ plaques were visualized with a thioflavin-S staining. Vesicular acetylcholine transporter (VAChT) bouton density and levels of chemokine (C-X-C motif) ligand 1 (CXCL1), interleukin-6 (IL-6), and 4-hydroxynonenal (4-HNE) were probed using quantitative immunohistochemistry. During the early Aβ post-plaque stage, we find that NP03 rescues functional deficits in object recognition, reduces loss of cholinergic boutons in the hippocampus, reduces levels of soluble and insoluble cortical Aβ42 and reduces hippocampal Aβ plaque number. In addition, NP03 reduces markers of neuroinflammation and cellular oxidative stress. Together these results indicate that microdose lithium NP03 is effective at later stages of amyloid pathology, after appearance of Aβ plaques. Show more

Keywords: Aβ pathology, Alzheimer’s disease, brain repair, cholinergic boutons, cognition, lithium microdose, neuroinflammation, oxidative stress, transgenic rat model

DOI: 10.3233/JAD-190862

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 723-739, 2020

Authors: Crespo-Cuevas, Ane Miren | López-Cancio, Elena | Cáceres, Cynthia | González, Anna | Ispierto, Lourdes | Hernández-Pérez, María | Mataró, María | Planas, Anna | Canento, Tamara | Martín, Lorena | Arenillas, Juan Francisco | Alvarez, Ramiro | Vilas, Dolores

Article Type: Research Article

Abstract: Background: Non-invasive biomarkers of cognitive impairment are needed. We aim to evaluate transcranial sonographic markers as predictors of cognitive impairment in a prospective cohort. Objective: To study the changes in the third ventricle diameter and the SN echogenicity between the baseline and the control visit, as well as its association with cognitive performance and the diagnosis of cognitive impairment in a prospective cohort. Methods: From the longitudinal population-based Asymptomatic Intracranial Atherosclerosis Study, we selected those subjects that received a complete transcranial sonography (TCS) and extensive cognitive testing, both at baseline and follow-up. We evaluated third ventricle …(IIIv) width, echogenicity of substantia nigra (SN), and temporal changes of these parameters. Results: We included 289 participants with a median follow-up time of 7.16 years. Those subjects who developed cognitive decline (n  = 23, 7.96%) had a larger IIIv at baseline than those who did not (0.54±0.14 cm versus 0.41±0.15 cm; p  = 0.001). A cut-off point of 0.465 cm for the IIIv width was identified as an independent predictor of long-term cognitive impairment after adjustment for age, gender, educational level, and vascular risk score. Change in IIIv diameter after follow-up was not associated with diagnosis of cognitive impairment. The area of SN and the presence of hyperechogenicity of the SN remained stable over time and was not associated with the diagnosis of cognitive impairment. Conclusion: IIIv width assessed by TCS emerged as an independent predictor of long-term cognitive impairment. Show more

Keywords: Cognitive decline, dementia, sonography, third ventricle, transcranial

DOI: 10.3233/JAD-190949

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 741-749, 2020

Authors: Wu, Wanqing | Ding, Ding | Zhao, Qianhua | Wang, Ruru | Liang, Xiaoniu | Xiao, Zhenxu | Luo, Jianfeng | Guo, Qihao | Hong, Zhen

Article Type: Research Article

Abstract: Background: There is significant evidence that physical activity has profound effects on the neurochemistry and plasticity of the brain and may prevent cognitive decline. Objective: This study aimed to determine the association between physical activity and incident dementia among older Chinese adults. Methods: In the prospective phase of the Shanghai Aging Study, 1,648 community-dwellers aged 60 years or older were followed for an average of 5 years. Their physical activity was assessed based on questionnaires. The physical activities were further transformed into metabolic equivalent values. A consensus diagnosis of incident dementia was ascertained based on medical, …neurological, and neuropsychological data and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Results: We identified 166 incident dementia cases; the incidence rate was 19.4 per 1000 person-years. A multivariate Cox regression model indicated that compared to low levels of physical activity, medium-to-high levels of physical activity were associated with a reduced risk of dementia (hazard ratio, 95% confidence interval = 0.62, 0.44–0.89) after adjusting for age, sex, years of education, apolipoprotein E ɛ 4, and other confounders. Conclusion: Our findings demonstrate that medium-to-high level of physical activity is protective against dementia in older adults. Show more

Keywords: Chinese, cognition, cohort studies, dementia, incidence, physical activity

DOI: 10.3233/JAD-190937

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 751-758, 2020

Authors: Wang, Yan-Li | Chen, Wei | Cai, Wen-Jie | Hu, Hao | Xu, Wei | Wang, Zuo-Teng | Cao, Xi-Peng | Tan, Lan | Yu, Jin-Tai | Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: White matter hyperintensities (WMHs), mainly caused by cerebrovascular injury, may lead to cognitive impairment. In order to identify whether the volume of WMHs is associated with cognitive decline over years, this longitudinal study involved 818 individuals from the ADNI-2 dataset from August 2010 to May 2017. Cross-sectional and longitudinal associations of WMHs with 8 cognitive domains were explored, using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog13), Rey Auditory Verbal Learning Test (RAVLT), Functional Assessment Questionnaire (FAQ), executive function (ADNI-EF), and memory function (ADNI-Mem). The association analyses were …performed using multiple linear regression models, linear mixed models, Spearman rank correlation, and Kaplan-Meier survival curves. The volumes of WMHs were greater in patients with Alzheimer’s disease (AD) dementia compared with controls (p  < 0.001) and mild cognitive impairment (p  = 0.006) patients at baseline. The bigger volumes of WMHs correlated with worse performances on ADAS-Cog13 and ADNI-EF (p  = 0.029; p  = 0.003) at baseline and MMSE, MoCA, CDRSB, ADAS-Cog13, FAQ, and ADNI-Mem (overall p  < 0.05) longitudinally, after adjusting for age, sex, educational level, apolipoprotein E ɛ 4 genotype, hypertension, hyperlipidemia, diabetes, smoking, infarction, and diagnosis. Additionally, the correlations between the change rate of WMHs and change rates of MMSE, MoCA, CDRSB, FAQ, ADNI-EF, and ADNI-Mem were statistically significant. Furthermore, patients with high WMH volumes showed an increased likelihood of dementia. The results of the study suggest that WMH volume is associated with cognitive decline, and it contributes to the conversion to AD. Show more

Keywords: Alzheimer’s disease, Alzheimer’s Disease Neuroimaging Initiative, cognition, white matter hyperintensities

DOI: 10.3233/JAD-191005

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 759-768, 2020

Authors: Bisbe, Marta | Fuente-Vidal, Andrea | López, Elisabet | Moreno, Marta | Naya, Marian | de Benetti, Claudio | Milà, Raimon | Bruna, Olga | Boada, Mercè | Alegret, Montserrat

Article Type: Research Article

Abstract: Background: Recent research on mild cognitive impairment (MCI) has primarily focused on searching for measures to prevent or delay the progression of MCI to dementia. Physical exercise has shown to be effective in the prevention of age-related cognitive decline in elderly adults with MCI. However, the most effective type and dose of exercise for the improvement of cognition are yet to be determined. Objective: To compare the cognitive effects of choreographed exercise (Choreography group) with a multimodal physical therapy program (Physical Therapy group) in elderly adults with amnestic MCI, a population with an increased risk of developing dementia. …Methods: We conducted a randomized clinical trial with two parallel groups under allocation concealment and assessor blinding. Participants were allocated into Choreography or Physical Therapy group and performed exercises twice per week in 60-minute sessions during 12 weeks. Results: Thirty-six participants with amnestic MCI, ages 65 to 85, were assessed at baseline and after 12 weeks of intervention, by comprehensive validated neuropsychological and physical assessments. A Repeated measures General Lineal Model showed statistically significant differences in cognitive and physical outcomes. Both groups significantly improved in visual delayed recall. The Choreography group exhibited significantly more benefits on verbal recognition memory than the Physical Therapy group. Conclusion: Greater cognitive benefits were achieved in the choreographic intervention than in the multimodal physical therapy, mainly in those functions more related to the risk of conversion to dementia. Additional studies are needed to confirm whether the observed effects are related to delayed onset of Alzheimer’s disease in elderly adults with amnestic MCI. Show more

Keywords: Aging, Alzheimer’s disease, cognitive decline, dancing, mild cognitive impairment, motor skills, neuropsychology, physical exercise, physical therapy, physical activity

DOI: 10.3233/JAD-190552

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 769-783, 2020

Authors: Capp, Kimberly E. | Curiel Cid, Rosie E. | Crocco, Elizabeth A. | Stripling, Ashley | Kitaigorodsky, Marcela | Sierra, Luis A. | Melo, Jose G. | Loewenstein, David A.

Article Type: Research Article

Abstract: Background: Semantic intrusion errors on memory tests may represent very early cognitive changes associated with elevated Alzheimer’s disease pathology within the brain, including amyloid-β (Aβ). Subscales that measure proactive semantic interference (PSI) and intrusions related to PSI on the Loewenstein Acevedo Scales of Semantic Interference and Learning (LASSI-L) have been associated with high levels of brain amyloid load, structural changes on brain MRI in Hispanic and non-Hispanic groups. It is presently unknown whether intrusion errors or other measures of the LASSI-L can differentiate between African-American (AA) older adults diagnosed with amnestic mild cognitive impairment (aMCI) or classified as cognitively normal …(CN). Objective: This study examined the extent to which a high percentage of semantic intrusion errors on LASSI-L subscales susceptible to PSI and other LASSI-L measures could differentiate between AA aMCI and CN groups. Methods: Forty-eight AA older adults were recruited (27 CN and 21 aMCI) and received a through clinical and neuropsychological evaluation. The LASSI-L was administered independent of diagnostic classification. Results: With and without statistical adjustment for literacy, AA aMCI participants scored lower on all LASSI-L measures. ROC analyses revealed an area under the curve exceeding 90% and correctly classified 86% of AA aMCI with 82% specificity for AA CN participants. Conclusions: Percentage of intrusion errors on the LASSI-L subscales susceptible to PSI differentiated AA aMCI from AA CN. This adds to emerging evidence indicating that the LASSI-L may be culturally appropriate and can differentiate between aMCI and CN in diverse ethnic/cultural groups. Show more

Keywords: African Americans, Alzheimer’s disease, amyloid, cognitive assessment, diversity, intrusions, memory, mild cognitive impairment, neuropsychological tests, semantic interference

DOI: 10.3233/JAD-191022

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 785-790, 2020

Authors: Wohlgemuth, Anne | Michalowsky, Bernhard | Wucherer, Diana | Eichler, Tilly | Thyrian, Jochen René | Zwingmann, Ina | Rädke, Anika | Hoffmann, Wolfgang

Article Type: Research Article

Abstract: Background: Drug-related problems (DRP) are common in the elderly population, especially in people living with dementia (PwD). DRP are associated with adverse outcomes that could result in increased costs. Objective: The objective of the study was to analyze the association between DRP and healthcare costs in PwD. Methods: The analysis was based on the cross-sectional data of 424 PwD. Compliance, adverse effects, and drug administration of prescribed and over-the-counter drugs taken were assessed. DRP were identified and classified by pharmacists using an adapted German version of “PIE-Doc® ”. Healthcare utilization was assessed retrospectively used to calculated …costs from a public payer perspective using standardized unit costs. The associations between DRP and healthcare costs were analyzed using multiple linear regression models. Results: 394 PwD (93%) had at least one DRP. An inappropriate drug choice was significantly associated with increased total costs (b  = 2,718€; CI95% 1,448–3,988) due to significantly higher costs for hospitalization (b  = 1,936€; 670–3,202) and for medications (b  = 417€; 68–765). Problems with medication dosage and drug interactions were significantly associated with higher medication costs (b  = 679€; 31–1,328; and b  = 630€; 259–1,001, respectively). Conclusions: DRP could significantly lead to adverse outcomes for PwD and healthcare payers, reflected by a higher hospitalization and costs, respectively. Further research is needed to clarify on interventions and approaches efficiently avoiding DRP and on the effect on patient-reported and economic outcomes. Show more

Keywords: Dementia, health economics, hospitalization, potential inadequate medication

DOI: 10.3233/JAD-190819

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 791-799, 2020

Authors: Albaret, Guillaume | Sifré, Elodie | Floch, Pauline | Laye, Sophie | Aubert, Agnès | Dubus, Pierre | Azzi-Martin, Lamia | Giese, Alban | Salles, Nathalie | Mégraud, Francis | Varon, Christine | Lehours, Philippe | Roubaud-Baudron, Claire

Article Type: Research Article

Abstract: Despite extensive research, the origin of Alzheimer’s disease (AD) remains unknown. The role of infectious pathogens has recently emerged. Epidemiological studies have shown that Helicobacter pylori infection increases the risk of developing AD. We hypothesized that H. pylori -induced gastritis may be associated with a systemic inflammation and finally neuroinflammation. C57BL/6 mice were infected with H. pylori (n  = 15) or Helicobacter felis (n  = 13) or left uninfected (n  = 9) during 18 months. Gastritis, amyloid deposition, astroglial and microglial cell area, and systemic and brain cytokines were assessed. The infection (H. felis > H. pylori ) induced a …severe gastritis and an increased neuroinflammation but without brain amyloid deposition or systemic inflammation. Show more

Keywords: Alzheimer’s disease, dementia, gastric inflammation, GFAP, Helicobacter infection , iba-1, neuroinflammation

DOI: 10.3233/JAD-190496

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 801-809, 2020

Authors: Chen, Yanxing | Lin, Caixiu | Guo, Zhangyu | Zhao, Shuai | Zhu, Yueli | Huang, Fude | Shui, Guanghou | Lam, Sin Man | Pu, Jiali | Yan, Yaping | Liu, Zhirong | Zhang, Baorong

Article Type: Research Article

Abstract: Background: Studies have demonstrated that the levels of phospholipids, including phosphatidylinositols (PIs), were decreased in Alzheimer’s disease (AD) brain, presenting as a potential biomarker for AD. The plasma phospholipids levels have also been discovered to predict the conversion of cognitively normal elderly adults to amnestic mild cognitive impairment (aMCI) or demented patients. Objective: To investigate the expression profile of PIs in erythrocytes of AD and aMCI patients, which would serve as a blood-based method to distinguish AD and aMCI patients from normal controls (NC). Methods: In this study, we used anion-exchange high-performance liquid chromatography to analyze …PIs alterations in erythrocytes from a total of 86 prospectively recruited subjects (including 24 NC, 21 aMCI patients, and 41 AD patients). Results: We found that the levels of PI40 : 4, PI3/5P, and PI(3,4)P2 in aMCI patients, and the levels of PI4P, PI(3,4)P2, and PI3/5P in AD patients were significantly decreased compared to NC. The changed expression profile of PIs could effectively discriminate AD and aMCI patients from NC (AUC = 0.964, 0.938, respectively). Conclusion: The altered expression profile of erythrocytes PIs might be a potential blood-based biomarker for AD and aMCI. This alteration of PIs probably reflected the impaired deformability and oxygen-carrying capacity of erythrocytes in AD and aMCI patients. Show more

Keywords: Alzheimer’s disease, biomarker, erythrocytes, mild cognitive impairment, phosphatidylinositols

DOI: 10.3233/JAD-190926

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 811-818, 2020