Systematic Review
Yuto Yoshida, Yoshimune Hiratsuka, Reiko Umeya, Koichi Ono, Shintaro Nakao
The Association Between Dual Sensory Impairment and Dementia: A Systematic Review and Meta-Analysis
Abstract: Background: Sensory impairments have been linked to dementia. However, the impact of dual sensory impairment (DSI), combining both vision impairment and hearing impairment, on dementia has shown inconsistent results. Objective: To systematically review the evidence on the association DSI and dementia. Methods: A systematic literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library databases. Included studies were prospective or retrospective cohort studies and a case-control study. The primary outcome was the onset of dementia or its various subtypes, including Alzheimer’s disease (AD) and vascular dementia (VaD). Effect sizes, including hazard ratios (HRs), were pooled through a random-effects model. Results: A total of 11 observational studies with 346,659 participants were included. DSI was significantly associated with the incidence of dementia compared to no sensory impairment (9 studies; HR: 1.46; 95% confidence interval [CI]: 1.29-1.65). Among subtypes of dementia, DSI was associated with AD onset (4 studies; HR: 2.07; 95% CI: 1.45-2.94); however, this association was not found in VaD (2 studies; HR: 1.65; 95% CI: 0.96-2.85). Conclusions: These findings suggest that DSI is significantly associated with an increased risk of dementia. Further research is required to identify preventive strategies to decrease the incidence of dementia in individuals with sensory impairment.
Systematic Review
Gabriel Malvezzi da Silva Pinto, Luiz Otávio de Souza Crepalde, Ana Carolina Aparecida Marcondes Scalli, Marcos Paulo Braz de Oliveira, Guilherme Eustáquio Furtado, Sonia Brito-Costa, Nathalia Sernizon Guimarães, Natália Oiring de Castro Cezar
Body composition differences in older adults with and without Alzheimer’s disease: A systematic review and meta-analysis of observational studies
Abstract: Background: Research on body composition and fat distribution in Alzheimer's disease (AD) has presented conflicting findings. Objective: Compare body composition and anthropometric measurements in older adults with and without AD. Methods: A systematic review and meta-analysis were conducted following Cochrane guidelines and PRISMA standards. MEDLINE, Embase, Scopus, LILACS, WPRIM, and the Spanish Bibliographic Index of Health Sciences were searched up to September 2024, considering observational studies that compared body composition between AD groups and controls. Outcomes included body fat percentage, body mass index (BMI), impedance, resistance, and reactance. The methodological quality and level of evidence were assessed using the Joanna Briggs Institute scale and GRADE, respectively. A random-effects meta-analysis model was used to calculate mean differences (MD). Results: Fourteen studies involving 2761 older adults were included. Older adult women with AD showed a lower body fat percentage (p < 0.01; MD = -5.07) and BMI (p = 0.05; MD = -1.28) compared to controls. Older adult men with AD had higher impedance (p = 0.01; MD = 2.05), resistance (p = 0.02; MD = 45.10), and lower reactance (p = 0.03; MD = -2.05) compared to controls. No significant differences in body fat percentage or BMI were found between older adults with and without AD, regardless of gender. Conclusions: Women with AD showed lower body fat percentage and BMI, while men with AD had higher impedance, resistance, and lower reactance. These factors should be included in geriatric assessments for AD patients, though further research is needed to understand their link to cognitive outcomes in AD.
Commentary
Melissa Barker-Haliski
Seizing the opportunity to therapeutically address neuronal hyperexcitability in Alzheimer’s disease
Abstract: Seizures in people with Alzheimer’s disease are increasingly recognized to worsen disease burden and accelerate functional decline. Harnessing established antiseizure medicine discovery strategies in rodents with Alzheimer’s disease associated risk genes represents a novel way to uncover disease modifying treatments that may benefit these Alzheimer’s disease patients. This commentary discusses the recent evaluation by Dejakaisaya and colleagues to assess the antiseizure and disease-modifying potential of the repurposed cephalosporin antibiotic, ceftriaxone, in the Tg2576 mouse model. The use of established epilepsy models in Alzheimer’s disease research carries the potential to advance novel disease-modifying treatments.
Peng Wang, Yuan-li Dong, Shan-shan Li, Yi Jin, Wei-liang Sun, Bao-Sheng Zhao, Qiu-bing Li, Xin Chen
Integrating network pharmacology and component analysis to investigate the potential mechanisms of Sheng-Hui-Yi-Zhi decoction in the treatment of Alzheimer’s disease
Abstract: Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment. Objective: To elucidate the potential mechanisms of Sheng-Hui-Yi-Zhi (SHYZ) for the treatment of AD and explore the effective substances of SHYZ. Methods: Liquid chromatography-mass spectrometry (LC-MS) was used to identify the active components of SHYZ. Network pharmacology was employed to predict the potential targets and pathways of SHYZ in the treatment of AD. SAMP8 mice were used as a model for AD and were treated with SHYZ. The Morris water maze was utilized to assess the learning and memory capabilities of mice. Additionally, the levels of TNF-α, IL-1β, and IL-6 in the brain hippocampus of mice were quantified using ELISA. The protein expression of PI3K/p-PI3K, AKT/p-AKT, MAPK38/p-MAPK38, and NFκB p65/p-NFκB p65 in the hippocampus was analyzed using Western blotting. Additionally, qRT-PCR was employed to assess the gene expressions of TNF-α, IL-1β, and IL-6 in the hippocampus. Result: The network pharmacological prediction results showed that the treatment of AD with SHYZ was closely related to the inhibition of inflammatory response. Behavioral experiments revealed that SHYZ significantly reduced the time taken to escape, increased the number of times the platform was crossed, and prolonged the residence time in the target quadrant. Meanwhile, SHYZ treatment suppressed the expression of Aβ1-42 protein and inflammatory factors. SHYZ significantly inhibited the expression of proteins of PI3K, AKT, MAPK p38, and NF-κB p65. Conclusions: SHYZ has been shown to effectively ameliorate learning and memory impairment in SAMP8 AD mice by inhibiting the expression of Aβ1-42 and reducing the increase of inflammatory factors.
Oliver Davidson, Michael L Lee, Jason P Kam, Michael Brush, Anand Rajesh, Marian Blazes, David Arterburn, Eric Duerr, Laura E Gibbons, Paul K Crane, Cecilia S Lee on behalf of the Eye ACT study group (Handling Associate Editor: Manju Subramanian)
Associations between dementia and exposure to topical glaucoma medications
Abstract: Background: Some studies have suggested that glaucoma may be associated with neurodegeneration and a higher risk of dementia. Objective: To evaluate whether exposure to different categories of topical glaucoma medications is associated with differential dementia risks in people with glaucoma. Methods: We used data from Adult Changes in Thought, a population-based, prospective cohort study that follows cognitively normal older adults from Kaiser Permanente Washington (KPWA) until Alzheimer’s disease (AD) and related dementia development. We included participants with a diagnosis of glaucoma, KPWA pharmacy records of filling topical glaucoma medication (alpha-adrenergic agonists [AAA], beta-adrenergic antagonists, miotics, carbonic anhydrase inhibitors [CAI], and prostaglandins) and at least 10 years of pharmacy records. Eight-year sliding windows were derived for each medication class by computing days on each medication starting 10 years earlier and excluding the most recent 2 years. Cox regression used all 5 classes of medication simultaneously to predict AD and all-cause dementia. Results: We included 521 participants (mean age 78 [range 65-96], 62% female) with APOE genotype data. Beta-adrenergic antagonists were the most frequently prescribed (n=431) followed by prostaglandins (351), AAA (239), CAI (162), and miotics (142). Adjusting for time-varying exposure to other glaucoma medications, APOE, demographics, and smoking, each year of use of alpha-adrenergic agonists in an 8-year window was associated with a higher risk of developing dementia (HR = 1.33, 95% CI = 1.03-1.72). Conclusions: Among older adults with treated glaucoma, exposure to alpha-adrenergic agonists appears to be associated with risk for developing all-cause dementia.
Hafiz Khan, Fardous Farhana, Fahad Mostafa, Aamrin Rafiq, Effat W Nizia, Zawah Zabin, Rumana Atique, Megan Dauenhauer, Opemipo Omotara, Atqa Mujtaba, Komaraiah Palle, P Hemachandra Reddy
Gender differences in cognitive impairment among the elderly in rural West Texas counties
Abstract: Background: The prevalence of Alzheimer’s disease or dementia in the elderly population has been increasing both nationally and globally. Males and females are impacted differently when it comes to cognitive health, and this can be influenced by various risk factors. Objective: This study highlights the sociodemographic, chronic disease, and genetic biomarker risk factors associated with gender differences and cognitive impairments in the elderly population living in Cochran, Parmer, and Bailey counties of rural West Texas. Methods: Cross tabulation, Pearson’s chi-squared, two sample proportions, binary logistic regression, and multinomial logistic regression were utilized to analyze data. SPSS software was used to detect significant risk factors. Results: Using a bivariate logistic regression, the age group 70 and above of males and females for the Cochran and Parmer counties was found significantly associated with cognitive impairment. Anxiety, depression, diabetes, and cardiovascular disease were found to be significantly associated with an increased risk of cognitive impairment in females in Parmer County. Gender differences were observed in Cochran County for smoking but females in Bailey County were found to be more tobacco-dependent compared to other counties. However, in Cochran County the prevalence of cognitive impairment with rates of 66% for males and 70% for females was observed to be significantly lower in hypertensive group who consumed modified diet. Conclusions: Gender-based disparities in cognitive impairment are essential for gaining more insights into Alzheimer’s disease or dementia prevention and advancement of healthcare and medical approaches in the underserved rural communities of West Texas.
Ali Alghamdi, Stijn de Vos, Jens H J Bos, Catharina C M Schuiling-Veninga, Barbara C van Munster, Sumaira Mubarik, Hendrika J Luijendijk, Eelko Hak
A matched case-control study on polypharmacy and co-medications one year before drug treatment for Alzheimer’s disease
Abstract: Background: Alzheimer’s disease (AD) is the most prevalent form of dementia, characterized by amyloid-β plaques and neurofibrillary tangles. With an aging population, both AD and comorbidities are increasingly common. Managing comorbidities often requires multiple medications, leading to polypharmacy, defined as the concurrent use of five or more medications. Objective: This study aimed to estimate and compare the prevalence of polypharmacy one-year prior AD diagnosis compared to non-AD individuals. Method: A matched cross-sectional design used data from the IADB.nl prescription database (1994–2021), including individuals aged 65 and older with at least one AD medication prescription within a year. Controls were matched by age and sex at a 9:1 ratio. Analyses were stratified by time period (≤2010 and >2010) and further by sex and age. Results: 4,150 AD individuals were included and matched with 37,350 controls. AD individuals had a higher prevalence of polypharmacy compared to controls, ≤2010 (OR: 1.15, 95% CI: 1.03–1.29), >2010 (OR: 1.25, 95% CI: 1.16 – 1.36). Females with AD had slightly higher odds of polypharmacy than males. The prevalence was consistent across different time periods and age groups, with the highest odds in individuals aged 65-74. Conclusions: AD individuals in the Netherlands exhibit a significantly higher prevalence of polypharmacy in a year pre-AD diagnosis. The findings highlight the complexity of managing multiple comorbid conditions in AD individuals, emphasizing the need for regular review and optimization of medication regimens and the inclusion of non-pharmacological interventions to minimize adverse outcomes and improve quality of life.
Jingru Wang, Asta Debora, Lixuan Chen, Haisong Chen, Xuemiao Zhao, Mengying Yu, Yunjun Yang, for the Alzheimer’s Disease Neuroimaging Initiative
Association of small vessel disease progression with longitudinal cognitive decline across mild cognitive impairment
Abstract: Background: Cerebral small vessel disease (SVD) is the leading cause of vascular dementia. However, it is unclear whether the individual SVD or global SVD progression correlates with cognitive decline across mild cognitive impairment (MCI) subjects. Objective: To investigate the association of small vessel disease progression with longitudinal cognitive decline across MCI. Methods: We included 432 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, with 151 participants in the cognitively normal (CN) group and 281 participants in the MCI group. We evaluated magnetic resonance imaging–based SVD markers in both CN and MCI groups and explored their associations with 12-and 24-month cognitive decline using linear mixing effect (LME) models. Results: In the CN group, cerebral microbleed (CMB) progression was associated with the decline in language function (p < 0.05), and deep white matter hyperintensity (WMH) progression was associated with a decline in memory function (p < 0.05). In the MCI group, CMB progression was associated with a decline in memory function (p < 0.05) and lacunes progression was associated with executive function (p < 0.05), whereas the progression of global SVD score was not related to longitudinal cognitive function. Conclusions: The progression of CMB and WMH had an impact on cognitive decline in both CN and MCI groups, and lacunes progression only had an association with cognitive decline in the MCI group. Our study suggested that individual SVD markers may have a higher predictive value in longitudinal cognition compared with global SVD burden.
Danni Li, Binchong An, Lu Men, Matthew Glittenberg, Pamela L Lutsey, Michelle M Mielke, Fang Yu, Ron C Hoogeveen, Rebecca Gottesman, Lin Zhang, Michelle Meyer, Kevin Sullivan, Nicole Zantek, Alvaro Alonso, Keenan A Walker
The association of high-density lipoprotein cargo proteins with brain volume in older adults in the Atherosclerosis Risk in Communities (ARIC)
Abstract: Background: High-density lipoprotein (HDL) modulates the blood-brain barrier and cerebrovascular integrity, likely influencing the risk of Alzheimer’s disease (AD), neurodegeneration, and cognitive decline. Objective: This study aims to identify HDL protein cargo associated with brain amyloid deposition and brain volume in regions vulnerable to AD pathology in older adults. Methods: HDL was separated from the plasma of 65 non-demented participants of the Atherosclerosis Risk in Communities (ARIC) study using a fast protein liquid chromatography method. HDL cargo proteins were measured using a label-free, untargeted proteomic method based on mass spectrometry and data-independent acquisition. Linear regression with multiple imputations assessed the associations between each HDL cargo protein (log2-transformed) and brain amyloid deposition or temporal-parietal meta-ROI volume, adjusting for covariates. Results: The mean (SD) age of the participants was 76.3 (5.4) years old, 53.8% (35/65) female, 30.8% (20/65) black, and 28.1% (18/64, 1 missing) APOE4 carriers. We found few HDL cargo proteins associated with brain amyloid deposition and considerably more HDL cargo proteins associated with temporal-parietal meta-ROI volume. Two HDL cargo proteins mostly associated with temporoparietal meta-ROI volume were fibrinogen B (FGB) and plasminogen (PLG). A doubling of FGB in HDL was associated with a greater temporoparietal meta-ROI volume of 1638 mm3 (95% CI [688, 2589]). In comparison, a doubling of PLG in HDL was associated with a lower temporoparietal meta-ROI of 2351 mm3 (95% CI [-3669, -1034]). Conclusions: This study suggests that HDL cargo proteins associated with temporal-parietal meta-ROI volume are involved in complement and coagulation pathways.
Xiaotian Wu, Yanli Liu, Jiajun Che, Nan Cheng, Dong Wen, Haining Liu, Xianling Dong (Handling Associate Editor: Xianwen Li)
Unveiling neural activity changes in mild cognitive impairment using microstate analysis and machine learning
Abstract: Background: Mild cognitive impairment (MCI) is recognized as a condition that may increase the risk of developing Alzheimer's disease (AD). Understanding the neural correlates of MCI is crucial for elucidating its pathophysiology and developing effective interventions. Electroencephalogram (EEG) microstates, reflecting brain activity changes, have shown promise in MCI research. However, current approaches often lack comprehensive characterization of the complex neural dynamics associated with MCI. Objective: This study aims to investigate neurophysiological changes associated with MCI using a comprehensive set of microstate features, including traditional temporal features and entropy measures. Methods: Resting-state EEG data were collected from 69 MCI patients and healthy controls (HC). Microstate analysis was performed to extract conventional features (duration, coverage) and entropy measures. Statistical analysis, principal component analysis (PCA), and machine learning (ML) techniques were employed to evaluate neurophysiological patterns associated with MCI. Results: MCI displayed altered microstate dynamics, with significantly longer coverage and duration in Microstate C but shorter in Microstates A, B, and D compared to HCs. PCA revealed two principal components, primarily composed of microstate dynamics and entropy measures, explaining over 75% of the variance. ML models achieved high accuracy in distinguishing MCI patterns. Conclusions: Our comprehensive analysis of EEG microstate features provides new insights into neurophysiological changes associated with MCI, highlighting the potential of EEG microstates for investigating complex neural changes in cognitive decline.
Masaaki Matsunaga, Shinichi Tanihara, Yupeng He, Hiroshi Yatsuya, Atsuhiko Ota
Sex-specific association of comorbid heart failure on mortality after Alzheimer's disease diagnosis in older adults aged 75 years and above: A health insurance claims data analysis in Japan
Abstract: Background: Research on the influence of heart failure on mortality after Alzheimer's disease diagnosis is limited. Objective: To evaluate the association between comorbid heart failure and mortality following Alzheimer's disease diagnosis, particularly considering sex differences. Methods: We analyzed administrative claims data from Japan, involving 32,363 individuals (11,064 men and 21,299 women) aged 75 or older newly diagnosed with Alzheimer's disease, with 7% having comorbid heart failure. Cox proportional hazard models and population attributable fractions (PAFs) were used to evaluate the association between comorbid heart failure and mortality within one year following Alzheimer's disease diagnosis. Results: Individuals with Alzheimer's disease and heart failure had a multivariate-adjusted hazard ratio of 1.51 (95% confidence interval [CI], 1.32–1.73) for mortality during the one-year follow-up period compared to those with Alzheimer's disease and without heart failure. Subgroup analysis by sex revealed a higher mortality hazard ratio in women of 1.63 (95% CI, 1.36–1.95) than that in men of 1.39 (95% CI, 1.13–1.71). Further age and sex subgroup analysis indicated that women across all age brackets—75-79, 80-84, and ≥ 85 years—had higher mortality hazard ratios. The PAF for heart failure increased with age in both sexes, with women having higher PAFs than men, and the sex difference in PAF being most pronounced in the 75-79 age category (men: 1.4%, women: 4.0%). Conclusions: Hazard ratios and PAFs for mortality associated with comorbid heart failure in newly diagnosed Alzheimer's disease are higher in women than in men, which persists across all age subgroups.
Gemma García-Lluch*, Anna Marseglia*, Lucrecia Moreno Royo, Juan Pardo Albiach, Mar Garcia-Zamora, Miquel Baquero, Carmen Peña-Bautista, Lourdes Álvarez, Eric Westman, Consuelo Cháfer-Pericás *These authors contributed equally to this work.
Associations between antidiabetic medications and cerebrospinal fluid biomarkers of Alzheimer’s disease
Abstract: Background: It has been hypothesized that insulin resistance is pivotal in mediating amyloid and tau dysregulations in Alzheimer's disease (AD). Objective: To investigate the impact of different antidiabetic agents, their daily dosage intake, and treatment duration on cerebrospinal fluid (CSF) AD biomarkers among patients with type 2 diabetes. Methods: This cross-sectional study selected patients between 50 and 80 years with diabetes and CSF AD biomarkers screened between 2017 and 2023 in the VALCODIS Cohort. CSF biomarkers were total tau (t-tau), phosphorylated tau 181 (p-tau), and amyloid-β 42 (Aβ42). Analytical variables were obtained. Antidiabetic prescriptions were recorded in defined daily doses (DDD), according to the ATC/DDD 2021 system, and years of drug exposure duration before lumbar puncture. Logistic regressions were performed to establish the correlations between drug usage and AD biomarker alteration. Results: Among patients with diabetes, Insulin consumption was associated with lower odds of abnormal Aβ42 levels (OR 0.36 [95% CI 0.15, 0.76]) and tau pathology (OR 0.49 [95% CI 0.24-0.98]). Metformin was related to lower odds of pathological p-tau when diabetes was uncontrolled, acting on t-tau and t-tau/Aβ42 ratio when it was concomitant with insulin, and patients had controlled diabetes. Lower odds of pathological levels of tau were observed when additional oral antidiabetic drugs were added among metformin users. iSGLT2 was associated with tau pathology. Conclusions: The impact of antidiabetics on AD-related pathological biomarkers may depend on diabetes management.
Dan Li#, Xining Liu#, Jiaming Yu, Yifei Zhang, Nan Hu, Yuanyuan Lu, Fangling Sun, Min Zhang, Xiaowei Ma, Fen Wang #These authors contributed equally to this work.
Item response theory for the color-picture version of Boston Naming Test in a Chinese sample with neurodegenerative diseases
Abstract: Background: Although Boston Naming Test has been thoroughly validated at a global level, there is limited assessment of item-level properties using modern psychometric methods. Objective: This study aimed to investigate the construct validity and item-level properties of the color-picture version of Boston Naming Test (CP-BNT) in a Chinese cohort with neurodegenerative diseases. Methods: This retrospective study included 424 participants, consisting of 118 normal controls, 152 with Alzheimer's disease, 101 with primary progressive aphasia, and 53 with other neurodegenerative diseases. All participants underwent a comprehensive neuropsychological assessment that included the CP-BNT. Factor analysis and item response theory were conducted. Results: The CP-BNT exhibits a multidimensional structure with three factors: Factor 1, consisting of nine items with moderate difficulty levels, demonstrated peak measure function for mild anomia (the highest information value=33.7, ability estimated value=-0.8, reliability=0.97); Factor 2, comprising eleven items with lower difficulty levels, performed well in cases of mild to moderate anomia (the highest information value=34.1, ability estimated value=-1.2, reliability=0.97); and Factor 3, including ten items with higher difficulty levels, provided the most measure information for normal naming (the highest information value=9.9, ability estimated value= 0, reliability=0.90). All items, except item igloo, showed good discrimination (discrimination parameter ranged from 5.46 to 1.15). Most items had a different difficulty position versus the original version, thereby generating a novel item sequence with an ascending difficulty hierarchy for Chinese samples. Conclusions: These findings support that the CP-BNT has good validity, reliability, and cultural appropriateness in the Chinese context, improving its utility in clinical assessments and interventions.
João Paulo Martins, Fernanda Bono Fukushima, Leandra Navarro Benatti, Rodrigo Bazan, Katherine Di Santi Correa da Silva, Edison Iglesias de Oliveira Vidal (Handling Associate Editor: Emmeline Ayers)
Prevalence of motoric cognitive risk syndrome among older adults in Brazil and evaluation of effect modification by race
Abstract: Background: Motoric cognitive risk syndrome (MCRS) is a pre-dementia syndrome of growing interest, yet it remains understudied in Latin America with a significant lack of information on the interaction between its risk factors and race. Objective: To estimate the prevalence of MCRS among older adults in Brazil, investigate its association with various clinical and sociodemographic variables, and explore the potential of effect modification by race. Methods: This cross-sectional, population-based study was conducted among community-dwelling older adults in Brazil, with data collected between 2015 and 2016. The diagnosis of MCRS was established following the standard recommended by the original study that first described it. We used Poisson regression models to analyze the association between MCRS and a list of 21 variables identified from a systematic review. Results: A total of 4677 participants aged 60 years and older were included. The prevalence of MCRS in the Brazilian population of older adults was 4.34% (95% CI: 3.20%–5.48%). Higher levels of education and physical activity showed protective associations with MCRS, while depression and stroke demonstrated risk associations. A significant cross-over interaction between race and depression regarding MCRS was observed, such that the association of depression with MCRS was approximately three times higher among White individuals than Black individuals. Conclusions: Our results challenge previous estimates that Latin America is the region with the highest prevalence of MCRS among older adults and signal the need for further studies to better investigate the modification of effect of the association between depression and MCRS by race.
Chang Cai, Takashi Kato, Yutaka Arahata, Akinori Takeda, Takashi Nihashi, Keita Sakurai, Emi Tanaka, Kersten Diers, Kosuke Fujita, Taiki Sugimoto, Takashi Sakurai, Kengo Ito, Akinori Nakamura
Altered functional connectivity between primary visual cortex and cerebellum in Alzheimer's disease
Abstract: Background: It is known that eyes-open (EO) and eyes-closed (EC) conditions invoke different organizations of brain functional networks, such as sensorimotor, attention, and salience networks in healthy participants. Functional connectivity (FC) extracted from resting-state functional magnetic resonance imaging data, under either EO or EC conditions, has been widely applied to explore the neural substrates of Alzheimer's disease (AD). However, the impact of eye conditions on FC within the AD continuum remains not fully understood. Objective: This study aims to investigate the effects of eye conditions on FC across the AD continuum. Methods: FC with the primary visual cortex (V1) seed was analyzed for both EO and EC conditions in 59 amyloid-β (Aβ)-positron emission tomography (PET)-negative cognitively normal (CN-), 14 Aβ-PET-positive CN+, 24 mild cognitive impairment (MCI+), and 15 AD individuals. Results: EO and EC differently modulated FC between the V1 and cerebellum, especially the posterior vermis, in all groups. In CN-, CN+, and MCI+ groups, EO significantly facilitated FC between V1 and the cerebellum compared with the EC condition. However, the AD group showed the reverse pattern. Moreover, a sub-analysis demonstrated that the FC significantly correlated with a truncal balance measure under EO, but not EC, in participants with MCI+ and AD. Conclusions: The results show that the FC between the V1 and cerebellum changed in AD. This finding may partially explain the impaired truncal balance and tendency to fall down in AD. This study suggests that analyzing FC under EO and EC conditions may provide a new functional biomarker for AD.
Worku Animaw Temesgen, Ho Yu Cheng, Yuen Yu Chong
Cognitive function and its longitudinal predictability by intensity of physical activity in Chinese middle-aged and older adults
Abstract: Background: The aging population faces several health problems, including cognitive decline that can progress to Alzheimer's disease. Regular physical activity is widely recognized for its extensive benefits, including physical and mental health improvements especially for older adults. Objective: This study aimed to examine the prediction of physical activity intensities on cognitive function of older adults. Methods: Data from 8 years prospective survey among Chinese population aged 45 years and older is used. Cognitive function was measured by word recall, orientation, numeric subtraction, and copying a picture. Physical activity was assessed with three intensity levels. General estimating equations (GEE) with unstructured correlation matrix is used to test the prediction of physical activity intensity on cognitive function. Results: Cognitive function of participants significantly declined from 9.81 at baseline to 8.81 after 8 years. Moderate-intensity physical activity for 3 days/week was strongest positive predictor of cognitive function with a betta coefficient of 0.64. Light-intensity physical activity also positively predicted cognitive function, however vigorous physical activity for more than 3 days/week negatively predicted cognitive function. Conclusions: Cognitive function of the Chinese population is found to continuously decline after 60 years old age. Fortunately, this decline can be delayed with age-tolerable light to moderate-intensity physical activities.
Xiaojuan Han, Yuanjing Li, Jiafeng Wang, Xinyu Liu, Yu Zhang, Qiwei Dong, Yiming Song, Lin Cong, Qinghua Zhang, Shi Tang, Lin Song, Tingting Hou, Yongxiang Wang, Yifeng Du, Chengxuan Qiu
Associations between lifelong cognitive reserve, Alzheimer’s disease-related plasma biomarkers, and cognitive function in dementia-free older adults: A population-based study
Abstract: Background: Cognitive reserve (CR), typically measured through socio-behavioral proxies, can partially explain better cognitive performance despite underlying brain aging or neuropathology. Objective: To examine the associations of CR with mild cognitive impairment (MCI) and cognitive function while considering Alzheimer’s disease (AD)-related plasma biomarkers. Methods: This population-based cross-sectional study included 4706 dementia-free individuals from MIND-China. Data on AD-related plasma biomarkers were available for 1204 individuals. A composite CR score was generated by integrating education, occupational complexity, mental activity, and social support, using structural equation modeling. A neuropsychological test battery was used to assess the function of episodic memory, executive function, attention, and verbal fluency. MCI and subtypes of MCI were defined according to the Petersen’s criteria. Data were analyzed using general linear and logistic regression models. Results: Controlling for AD-related plasma biomarkers, higher educational attainment was associated with better performance in all four examined cognitive domains (p<0.001) and with lower likelihoods of MCI, amnestic MCI (aMCI), and non-aMCI (p<0.05); late-life mental activity was significantly related to lower likelihoods of MCI and aMCI (p<0.05). Midlife occupation and late-life social support were not significantly associated with MCI or subtypes (p>0.05). Higher composite CR scores were related to better performance in all the examined cognitive domains as well as lower likelihoods of MCI, aMCI, and non-aMCI (p<0.05). Conclusions: Greater composite CR, derived from the CR indicators across different stages of the lifespan, is associated with better cognitive function independent of AD-related plasma biomarkers, driven mainly by early-life educational attainment.
Jay Shah, Janina Krell-Roesch, Erica Forzani, David S Knopman, Cliff R Jack, Jr., Ronald C Petersen, Yiming Che, Teresa Wu, Yonas E Geda
Predicting cognitive decline from neuropsychiatric symptoms and Alzheimer’s disease biomarkers: A machine learning approach to a population-based data
Abstract: Background: The aim of this study was to examine the potential added value of including neuropsychiatric symptoms (NPS) in machine learning (ML) models, along with demographic features and Alzheimer’s disease (AD) biomarkers, to predict decline or non-decline in global and domain-specific cognitive scores among community-dwelling older adults. Objective: To evaluate the impact of adding NPS to AD biomarkers on ML model accuracy in predicting cognitive decline among older adults. Methods: The study was conducted in the setting of the Mayo Clinic Study of Aging, including participants aged ≥ 50 years with information on demographics (i.e., age, sex, education), NPS (i.e., Neuropsychiatric Inventory Questionnaire; Beck Depression and Anxiety Inventories), at least one AD biomarker (i.e., plasma-, neuroimaging- and/or cerebrospinal fluid [CSF]-derived), and at least 2 repeated neuropsychological assessments. We trained and tested ML models using a stepwise feature addition approach to predict decline versus non-decline in global and domain-specific (i.e., memory, language, visuospatial, and attention/executive function) cognitive scores. Results: ML models had better performance when NPS were included along with a) neuroimaging biomarkers for predicting decline in global cognition, as well as language and visuospatial skills; b) plasma-derived biomarkers for predicting decline in visuospatial skills; and c) CSF-derived biomarkers for predicting decline in attention/executive function, language, and memory. Conclusions: NPS, added to ML models including demographic and AD biomarker data, improves prediction of downward trajectories in global and domain-specific cognitive scores among community-dwelling older adults, albeit effect sizes are small. These preliminary findings need to be confirmed by future cohort studies.
Wukun Ge, Yingyan Yan, Yaoyao Hu, Shuainan Lin, Peizhi Mao
Unveiling the safety profile of lecanemab: A comprehensive analysis of adverse events using FDA adverse event reporting system data
Abstract: Background: Lecanemab, a novel monoclonal antibody targeting amyloid-β, has shown promise in treating Alzheimer's disease. Comprehensive post-marketing safety data analysis is crucial to understand its real-world risk profile. Objective: This study aimed to evaluate the safety profile of lecanemab using data from the FDA Adverse Event Reporting System (FAERS), with a focus on nervous system disorders and amyloid-related imaging abnormalities. Methods: We conducted a disproportionality analysis using the FAERS database to evaluate the safety signals associated with lecanemab. Reporting odds ratio (ROR), proportional reporting ratio, empirical Bayesian geometric mean, and information component were calculated at both system organ class (SOC) and preferred term (PT) levels. Additionally, we performed a time-to-onset analysis using Weibull shape parameter estimation. Results: Analysis at the SOC level revealed significant signals for nervous system disorders (ROR: 7.32, 95% CI: 6.69-8.00). At the PT level, strong signals were observed for amyloid-related imaging abnormalities, particularly those associated with microhemorrhages and oedema (ROR: 4122.81 and 3922.78, respectively). Headache was the most frequently reported adverse event (200 cases), followed by chills (107 cases) and fatigue (97 cases). Time-to-onset analysis showed a median time of 33 days (range: 1-1283) for all adverse events, with neurological events occurring slightly later (median: 42 days, range: 1-1260). Conclusions: Our findings highlight a distinct safety profile for lecanemab, with a predominant impact on the nervous system and a notable association with imaging abnormalities. These results underscore the importance of vigilant monitoring and further research to optimize the risk-benefit profile of lecanemab in clinical practice.
Hóngyi Zhào#, Haiyang Zhang#, Yu Ding, Hong Li, Yonghua Huang #These authors contributed equally to this work.
Circadian rest-activity rhythm pattern in the elderly with cerebral small vessel disease: Using multiple estimated methods
Abstract: Background: Disruption of circadian rest-activity rhythm (RAR) has been found in many neurological disorders. Objective: In this study, actigraphic data were collected and analyzed to identify the RAR pattern in the elderly with cerebral small vessel disease. Methods: 115 cerebral small vessel disease (CSVD) cases were recruited. The presence of lacune infarct, white matter hyperintensities, and cerebral microbleeds in magnetic resonance imaging (MRI) images were rated independently, as well as using a simple MRI score of 0–3 points. Each subject wore an Actigraph device in their nondominant hand for 4–7 days to collect raw data. RAR parameters were generated using both extended cosinor model (RAR α, RAR β, amplitude, acrophase, up-mesor, down-mesor, and pseudo-F statistic) and non-parametric methods (interdaily stability, intradaily variability, and relative amplitude). Results: Elder patients with a simple MRI score of 2–3 points showed a statistically lower amplitude compared with individuals with a simple MRI score of 0 points in the extended cosinor model. For the non-parametric method, elderly people with a simple MRI score of 1–3 points exhibited higher intradaily variability relative to those participants with a simple MRI score of 0 points. However, no differences were found regarding sleep quality among individuals with different simple MRI scores. White matter hyperintensities, lacune infarct, and cerebral microbleeds were independently associated with RAR β, RAR α, and intradaily variability, respectively. Conclusions: The RAR pattern was disturbed in elderly adults with CSVD. Abnormal RAR parameters were independently associated with CSVD MRI markers.
Diane Carol Gooding, Carol A Van Hulle, Megan Zuelsdorff, Jordan P Lewis, Fabu P Carter, Hector Salazar, Shenikqua Bouges, Taryn T James, Alexander Gee, Carey E Gleason (Handling Associate Editor: Brian Downer)
Perceptions about preclinical Alzheimer’s disease biomarker collection procedure influences willingness to participate: Findings from an ethnoracially diverse study
Abstract: Background: Past research suggests that ethnoracialized groups differ in their willingness to engage in preclinical Alzheimer’s disease (AD) research overall. Studies indicated that participation willingness was affected by attitudes toward research and perceived invasiveness of biomarker collection techniques. However, comparative quantitative studies are few, and minoritized groups are under-included. Objective: In a cross-sectional online survey, we sought to explore community-based adults’ willingness to engage in preclinical AD biomarker testing, comparing their attitudes about research and different types of biomarker procedures. Methods: We conducted an online survey with a diverse group of participants. African American (AA), American Indian/Alaska Native (AI/AN), Latinx (LTX), and Non-Hispanic White (NHW) adults aged 26-90 were asked about their research attitudes, biomarkers, and willingness to participate in specific biomarker test procedures (i.e., brain imaging via PET scanning, blood draws, and cerebrospinal fluid collection by lumbar puncture). We also assessed participants' perceived safety, burden, and distress for each of the three biomarker collection methods. To understand the association between research willingness and ethnoracial identity, we ran linear regression models for each procedure, adjusting for age, gender, educational attainment, and attitudes toward research. Results: The AA group expressed greater willingness to engage in biomarker testing involving blood draws than the NHW group. The AI/AN group was significantly less willing to undergo lumbar puncture than the NHW group; this difference remained after adjusting for various sociodemographic factors and research attitudes. Conclusions: Respondents’ willingness to engage in preclinical AD biomarker research was affected by their perceptions about the testing collection procedure.
Wenkai Yang, Weihua Yu, Yang Lv
Neuroprotective effects of chitinase-1 and calcitonin gene-related peptide on Alzheimer’s disease by promoting lysosomal function
Abstract: Background: The amyloid cascade hypothesis still dominates in Alzheimer’s disease (AD), and the acceleration of the clearance efficiency of amyloid-β (Aβ) has been always considered as an effective treatment option to slow the occurrence and progression of AD. Objective: This study aims to explore the role of zkscan3 and its related pathways in AD of the microglia-mediated pathogenesis, and whether the combined effect of drugs can exert neuroprotective function. Methods: N9 mouse microglia and HT-22 mouse hippocampal neurons were randomly divided into 6 groups, qRT-PCR technique was used to detect the gene expression level of zkscan3 and the genes related to lysosome generation and function. Fourteen C57 mice were randomly divided into two groups, and drug intervention model mice were randomly selected to establish from the AD group. Transmission electron microscope was used to detect the cell status and lysosome function in the hippocampus together with the other two groups. Results: Compared with the AD model group, the gene expression of zkscan3 in the drug intervention group was downregulated, and the degree of neuronal injury in the hippocampus was reduced, the structure and number of synapses were improved, and the function of intracellular lysosome was enhanced. Conclusions: Zkscan3 and its related genes play a vital role in the development of AD. CGRP and CHIT-1, as a combined intervention, imparts effects through zkscan3-related pathways to improve lysosomal function and exert certain neuroprotective effects.
Mohamad Khaled, Hadi Al-Jamal, Dana Matar, Antonia Ibrahim, Layla Tajer, Nicole Issa, Reem El-Mir, Joudi Hantour
Unveiling the link between APOE ε4, environmental factors, and Alzheimer’s disease in North Lebanon: A case-control study
Abstract: Background: Alzheimer’s disease (AD) is a multifactorial and progressive neurodegenerative disorder influenced by a variety of genetic and environmental factors. The apolipoprotein E (APOE) gene is known to have a pivotal impact on disease onset, yet clinical studies on its impact on AD remain scarce in Lebanon. Objective: This study investigates the interplay between environmental risk factors, the APOE gene, and AD in North Lebanon. Methods: A case-control study was conducted with 136 individuals, including 57 AD patients and 79 normal individuals, among which 55 individuals were verified to be cognitively normal via the Mini-Mental State Examination (MMSE). A comprehensive survey was used to collect data on lifestyle factors, medical history, and other possible diseases and deficiencies. Blood samples were collected from all participants, then their DNA was isolated and stored. Real-time PCR was adopted for genotyping. Results: The total APOE ε4 allele prevalence was reduced from 19.1% to 16.1% after MMSE adjustment. Based on the univariate analysis, factors like age, illiteracy, vitamin and iron deficiencies, blood pressure, and chronic diseases were identified as prominent risk factors, while the allele showed no significant correlation with AD. However, in the multivariable analysis, this allele emerged as a key risk factor (p=0.04). Factors like age≥65, vitamin deficiency, iron deficiency, blood pressure, and other chronic diseases were consistently significant. Conclusions: Our results provide significant evidence that the influence of APOE ε4 on AD is governed by several environmental factors such as age, vitamin and iron deficiencies, high blood pressure, and chronic diseases.
Neha Abeywickrama, Mel N Ellul Miraval, Hari Subramaniam, Qadeer Arshad, Stephanie Pollard, Geeta Chauhan, Shifa Jussab, Elizabeta B Mukaetova-Ladinska
Efficacy of music-based intervention for people living with dementia in an inpatient setting: A pilot study
Abstract: Background: Pharmacological treatment of behavioral and psychological symptoms of dementia is of limited benefit. The addition of non-pharmacological interventions is often essential for optimal symptom control. Music is a viable way to help patients communicate and improve their quality of life. Objective: This study aims to find the most effective way to use music in a busy dementia ward. Methods: 17 inpatients (aged 63-93 years) with a clinical diagnosis of Alzheimer’s disease and dementia took part over five weeks. Music lyrics presented via free-field speakers were individualized to personal preferences. Instruments (e.g., maracas) were used in some group sessions. We used the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Music in Dementia Assessment Scales (MiDAS) to evaluate patients’ behavior before and after musical intervention. Results: There was a significant difference in mean NPI-Q scores before and after the music intervention. Specifically, Delusion, Motor Disturbances, and Agitation scores were significantly reduced after music intervention. This was accompanied by significant improvements in Interest, Response, and Enjoyment of MiDAS items during specific intervals. Conclusions: Clinical professionals can successfully deliver music-based intervention to inpatients with advanced dementia to help manage their behavioral symptoms in the short term. Music-based interventions’ use for inpatient wards must be further investigated as an economical and personalized non-pharmacological therapeutic tool for patients with dementia.
Yunyi Li, Apoorva Bharthur Sanjay, Mohit Manchella, Aryan Mishra, Paige E Logan, Hee Jin Kim, Shannon L Risacher, Sujuan Gao, Liana G Apostolova for the Alzheimer’s Disease Neuroimaging Initiative
Effect of genetic and vascular risk factors on rates of cognitive decline in early-onset and late-onset Alzheimer’s disease
Abstract: Background: Although previous studies have shown that cognitive decline in Alzheimer’s disease (AD) is associated with various risk factors, they primarily focused on late-onset AD (LOAD). Objective: We aim to evaluate the differential impact of risk factors on the cognitive decline between early-onset AD (EOAD, onset < 65 years) and LOAD (onset ≥ 65 years) and explore the longitudinal effect of Apolipoprotein E allele 4 (APOE ε4) on cortical atrophy in both cohorts. Methods: Using data from 212 EOAD and 1101 LOAD participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we conducted multivariable mixed-effect models to evaluate the impact of APOE ε4, education, hypertension, diabetes, dyslipidemia, and body mass index on cognitive performance. Preprocessed MRI data were utilized for longitudinal parametric mapping. Results: APOE ε4 carriers in both groups showed significantly accelerated declines in language, verbal memory, executive function, and general cognition. By controlling other significant risk factors, APOE ε4 carriers showed faster declines in language and verbal memory in both groups. Females exhibited accelerated declines in Language and verbal memory in the EOAD and LOAD cohorts respectively. LOAD individuals with hypertension showed faster declines while overweight and obese participants displayed slower declines in both cohorts across all domains except visuospatial. Notably, APOE ε4 status was associated with longitudinal cortical atrophy in the LOAD cohort but not in the EOAD cohort. Conclusions: Known risk factors for AD were associated with cognitive decline in both EOAD and LOAD cohorts.
Pol Grau-Jurado, Shayan Mostafaei, Hong Xu, Minjia Mo, Bojana Petek, Irena Kalar, Luana Naia, Julianna Kele, Silvia Maioli, Joana B Pereira, Maria Eriksdotter, Saikat Chatterjee, Sara Garcia-Ptacek
Medications and cognitive decline in Alzheimer’s dementia: Cohort cluster analysis of 15,428 patients
Abstract: Background: Medications for comorbid conditions may affect cognition in Alzheimer’s disease (AD). Objective: To explore the association between common medications and cognition, measured with the Mini-Mental State Examination. Methods: Cohort study including persons with AD from the Swedish Registry for Cognitive/Dementia Disorders (SveDem). Medications were included if they were used by ≥5% of patients (26 individual drugs). Each follow-up was analyzed independently by performing 100 Monte-Carlo simulations of two steps each 1) k-means clustering of patients according to Mini-Mental State Examination at follow-up and its decline since previous measure, and 2) Identification of medications presenting statistically significant differences in the proportion of users in the different clusters. Results: 15,428 patients (60.38% women) were studied. Four clusters were identified. Medications associated with the best cognition cluster (relative to the worse) were atorvastatin (point estimate 1.44 95% confidence interval [1.15-1.83] at first follow-up, simvastatin (1.41 [1.11-1.78] at second follow-up), warfarin (1.56 [1.22-2.01] first follow-up), zopiclone (1.35 [1.15-1.58], and metformin (2.08 [1.35-3.33] second follow-up. Oxazepam (0.60 [0.50-0.73] first follow-up), paracetamol (0.83 [0.73-0.95] first follow-up), cyanocobalamin, felodipine and furosemide were also associated with the worst cluster. Cholinesterase inhibitors were associated with the best cognition clusters, whereas memantine appeared in the worse cognition clusters, consistent with its indication in moderate to severe dementia. Conclusions: We performed unsupervised clustering to classify patients based on their current cognition and cognitive decline from previous testing. Atorvastatin, simvastatin, warfarin, metformin, and zopiclone presented a positive and statistically significant associations with cognition, while oxazepam, cyanocobalamin, felodipine, furosemide and paracetamol, were associated with the worst cluster.
Tianchi Wan, Chunkai Wang
SMOC2 promotes microglia activity and neuroinflammation in Alzheimer’s disease
Abstract: Background: Alzheimer's disease (AD), the leading cause of dementia, is characterized by cognitive decline and the accumulation of amyloid-β (Aβ). It affects millions, with numbers expected to double by 2050. SMOC2, implicated in inflammation and fibrosis, may play a role in AD pathogenesis, particularly in microglial cell function, offering a potential therapeutic target. Objective: Alzheimer's disease (AD) leads to neurodegeneration, affecting cognition, language, and personality, underscoring the urgency for effective treatments. Our study investigates the role of secreted modular calcium-binding protein 2 (SMOC2) in microglial cells and its impact on AD pathology. Methods: We introduced SMOC2 overexpression and interference vectors into microglial cells treated with Aβ. Activity and phagocytosis were assessed using CCK8 and flow cytometry. SMOC2 mRNA levels were quantified by qPCR, and protein levels of SMOC2, TGF-β1, p-NF-κB/NF-κB were analyzed by western blot. Aβ content was determined by ELISA, and immunofluorescence detected TNF-α, IL-1β, CD163, and CD206. Results: Aβ treatment inhibited microglial activity and phagocytosis, but SMOC2 disruption enhanced these functions (p < 0.05). SMOC2 overexpression increased its expression and Aβ levels, while interference reduced them (p < 0.001). SMOC2 overexpression also decreased TGF-β1, CD163, and CD206, and increased p-NF-κB/NF-κB, TNF-α, and IL-1β (p < 0.05). Conclusions: SMOC2 plays a crucial role in microglial cell activity, phagocytosis, and polarization, potentially through the TGF-β1/NF-κB pathway, offering insights into AD pathogenesis.
Gang Wu, Yong Luo, Qian Guo, Mingming Yang, Yacoubou Abdoul Razak Mahaman, Yi Liu, Jian-Zhi Wang, Rong Liu, Xiang Gao, Xiaochuan Wang (Handling Associate Editor: Chunling Dai)
Conformation pattern changes in R1-pS262 tau peptide induced endogenous tau aggregation, synaptic damage, and cognitive impairments
Abstract: Background: To date, the effect of tau phosphorylation at different amino acid sites on the conformation and function of tau is still unclear in Alzheimer's disease (AD). Protein fingerprinting, also known as the protein folding shape code (PFSC) method, is a protein structure prediction technique based on protein sequence, which can reveal proteins’ most likely spatial conformation. Objective: To investigate the effect of phosphorylation on tau protein conformation using PFSC technology and further analyze the differences in the effect of phosphorylation on tau aggregation at specific sites. Methods: We performed a conformational analysis of wild-type and simulated mutant hTau441 using the PFSC method and synthesized the phosphorylated and non-phosphorylated tau fragments by the chemical solid phase method. Results: We found that the number of Ser262 protein fingerprints increased from six in tau S262A to nine in tau S262E, together with increased conformational changes and enhanced flexibility. The in vitro Thioflavin S assay showed that phosphorylated tau fragments R1-pS262 possessed a stronger activity of inducing tau aggregation. In contrast to the non-phosphorylated tau fragment R1-nS262, R1-pS262 promoted endogenous tau aggregation and decreased synaptic proteins. In rats, R1-pS262 caused cognitive impairments and neuronal loss in addition to endogenous tau aggregation and synaptic damage. Conclusions: Our study firstly reports that tau phosphorylation at Ser262 induces tau aggregation, and phosphorylated tau fragments R1-pS262 directly result in neuropathological changes. These provide new clues to the pathogenesis of tauopathy, such as AD, and a new molecular target for possible intervention.
Monisha S, Dwaiti Roy, Anjana J Menon, Sandhya G, Anant Gupta, Nimisha Basavaraju, Sadhana Singh, Jonas S Sundarakumar, Reddy Kommaddi, Thomas Gregor Issac
Exploring predementia: Understanding the characteristics of subjective cognitive decline plus from India
Abstract: Background: Subjective cognitive decline (SCD) is the early predementia syndrome. that occurs even before the development of objective cognitive decline. SCD plus refers to an additional set of criteria that increases the likelihood of developing mild cognitive impairment and further progressing to Alzheimer’s disease (AD). Studying the progression of SCD-plus participants will help in understanding the importance of diagnosing this condition at an early stage and delaying its onset. Objective: The present tries to examine neurocognitive changes in individuals who met the criteria of SCD-plus patients. The study also investigated the imaging correlates of these individuals in both cohorts. Methods: This study included 94 participants from Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) and Tata Longitudinal Study of Aging (TLSA) cohorts who satisfy the criteria of SCD plus. Mann-Whitney U test was used to compare the SCD plus participants and healthy controls. Regression analysis was performed to find the association between SCD plus and cognition. Results: The SCD-plus group performed poorer than the healthy group in episodic memory delayed recall (p=0.049), name face recognition (p=0.023), and letter fluency (p=0.004) tasks. The generalized linear model revealed that the SCD-plus group had lower left cerebellar cortex (p=0.010) and right inferior occipital cortex (p=0.016) volumes than the healthy control group. Conclusions: The participants in the SCD-plus group performed poorly on memory and language-related tasks, and the volumes of the associated brain regions decreased. This study suggested that the SCD-plus group had characteristics similar to AD group and can help in identifying AD at the earliest.
Book Review
In data we trust. A review of Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s by Charles Piller, 2025, One Signal Publishers/Atria Books, New York, 352 pp. Reviewed by George Perry and Rudolph Castellani
