Journal of Alzheimer's disease reports最新文献

Background: People suffering from Alzheimer's disease and related disorders (ADRD) were severely impacted by the COVID-19 pandemic, both physically and mentally.

Objective: This one-year study aimed to implement a protocol for controlling the spread of SARS-CoV-2 in a Belgian nursing home hosting exclusively patients suffering from ADRD, while minimizing pandemic-associated constraints.

Methods: After confirming the absence of positive cases in the nursing home and the development of a proper immunity against SARS-CoV-2, the staff members enrolled in the study were allowed to remove their mask. Then, a weekly non-invasive saliva RT-qPCR testing for SARS-CoV-2 detection was implemented to detect cases among the staff and residents. A monthly serological monitoring was set up to follow the levels of neutralizing and IgG antibodies against SARS-CoV-2.

Results: Three waves of COVID-19 infection were observed and quickly contained thanks to an effective quarantine policy. We confirmed the stronger humoral response developed by people infected before primo-vaccination compared to naïve-vaccinated ones and the weaker immune response of elderly individuals compared to younger participants, a difference abolished by booster. In parallel, we showed that ADRD people were able to develop a similar humoral response to SARS-CoV-2 vaccination or infection to that of people of similar age not suffering from these diseases.

Conclusions: We show that a strict protocol aimed at early case detection and anti-SARS-CoV-2 immunity follow-up has enabled ADRD residents from a Belgian nursing home to maintain social interactions thanks to the ability of study participants to remove masks, while minimizing the risk of infection.

Background: Regulatory approval of new investigational Alzheimer's disease (AD) therapies could be accelerated if reasonably likely surrogate endpoints could be used. Neurofilament light chain (NfL) has potential utility as a prognostic biomarker of neurodegeneration in AD.

Objective: To synthesize available evidence on the relationship between baseline NfL levels and longitudinal clinical decline.

Methods: A systematic literature review identified 19 eligible studies, contributing 37 longitudinal statistical models evaluating the association between baseline NfL (plasma or cerebrospinal fluid [CSF]) with subsequent clinical decline based on validated clinical scales including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale, and Clinical Dementia Rating. Results were pooled via meta-analysis, using partial correlation coefficients (PCC), separately for patient sub-groups (mild cognitive impairment, AD or combined).

Results: Across the AD continuum, higher baseline NfL levels were consistently associated with greater cognitive and global clinical decline in most analyses. This pattern was consistent for both plasma (pooled PCC = -0.17 [95% CI = -0.22, -0.12] for MMSE, any AD population) and CSF NfL (pooled PCC = -0.14 [95% CI = -0.24, -0.04] for MMSE, any AD population). The strength of association across multiple clinical endpoints and populations, measured by absolute value of pooled PCC, ranged from 0.13 to 0.25.

Conclusions: The results support the utility of NfL as a predictive biomarker for progression of clinical decline in AD patients.

Background: Tau phosphorylation is associated with neuronal division and differentiation in the fetal brain, in neuroblastoma cells, in the hibernating brains of ground squirrels and black bears, and in post-mitotic neurons in the Alzheimer's disease (AD) brain. The disassembly of the rigid microtubule structure of neurons for neuronal division and neurite remodeling requires the removal of the microtubule stabilizing protein tau via its phosphorylation.

Objective: To determine if tau phosphorylation is required during neural embryogenesis.

Methods: Using an in vitro human model of early embryonic development, human embryonic stem cells (hESC) were differentiated into embryoid bodies (EBs; akin to an early blastocyst) and then into neuroectodermal rosettes (akin to a rudimentary neural tube containing neuroectodermal precursor cells) upon treatment with progesterone. The neuroectodermal rosettes were then treated with and without LiCl (Cdk5 inhibitor) or roscovitine (GSK-3β inhibitor) and assayed for the expression of tau, P-tau, nestin (an early marker of neurogenesis), Cdk5 and GSK-3β.

Results: Tau was not expressed in hESC, but tau expression and its phosphorylation increase upon progesterone-induced differentiation of hESC into neuroectodermal rosettes. Both Cdk5 and GSK-3β, enzymes associated with tau phosphorylation, were expressed in hESCs, EBs, and neuroectodermal rosettes. The GSK-3β inhibitor LiCl, but not the Cdk-5 inhibitor roscovitine, prevented tau phosphorylation and nestin expression and the formation of neuroectodermal precursor cells.

Conclusions: These preliminary results suggest that progesterone induces tau expression and its phosphorylation during the differentiation of neuroectodermal rosettes from hESC and suggest that tau and its phosphorylation is obligatory for neuronal precursor cell mitosis. The parallels between neural embryogenesis and neurodegeneration are discussed in the context of tau phosphorylation and the aberrant re-entry of neurons into the cell cycle in AD.

A 52-year-old male with early-stage Alzheimer's disease and long-standing anxiety received 30 repetitive transcranial magnetic stimulation sessions over 8 months and 20-month Mediterranean diet intervention. Neuropsychological assessments [Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Clinical Dementia Rating, Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index) and resting-state electroencephalogram (rsEEG) were conducted at baseline, during treatment, and at 6-month follow-up. After treatment, MoCA and MMSE scores improved by 6 and 5 points; HAMA and HAMD scores declined by 7 and 3 points. rsEEG showed progressive increases in individual alpha peak frequency (8.69 to 10.22 Hz), enhancement of alpha power, and reduction in theta power. Cerebrospinal fluid amyloid-β₄₂ levels also normalized. The patient reported marked mental well-being.

Alzheimer's disease poses intricate challenges, affecting cognition and behavior, notably marked by agitation. The FDA's approval of brexpiprazole, an atypical antipsychotic, stands as a milestone, representing the first treatment for Alzheimer's-related agitation. brexpiprazole's modulation of serotonin-dopamine activity has proven effective in clinical trials, reducing agitation as measured by CMAI scores. Gradual dosage escalation is recommended, with potential side effects including nasopharyngitis, urinary tract infections, dizziness, somnolence, headache, and insomnia. Also useful for schizophrenia and treatment-resistant depression, providing ongoing treatment and potential well-being enhancement by managing agitation and other symptoms.

Background: With the progressive population aging, dementia is reaching epidemic dimensions worldwide. Non-pharmacological music-based interventions can have a positive impact on the rehabilitation of older adults with dementia. Nevertheless, there are few longitudinal cross-national studies testing their impact.

Objectives: This pilot study aims at shedding light on the effects of the SOUND person-centered music-based intervention on well-being, cognition, executive functions and mood of older adults with mild-moderate dementia in three European countries.

Methods: An original intervention consisting in 12 sessions of active and passive music activities (singing, rhythmic exercises with Orff's tools, narratives elicited by music, etc.), led by a trained facilitator, was implemented in Italy, Portugal and Romania with 41 older adults with mild-moderate dementia attending elder facilities. Data on well-being, cognition, executive functions and mood of participants were collected before, at the end and two weeks after the intervention through psychometric tools. Temporal comparisons were assessed by T-test for paired samples.

Results: The SOUND intervention significantly improved participants' well-being, cognition and executive functions over time and remained stable at the follow-up at cross-national level. The potential of the intervention on mood is not clear due to depression and anxiety increasing among Romanian participants.

Conclusions: Cross-national, longitudinal, multidisciplinary mixed-method studies demonstrating the effects of music-based rehabilitative interventions for older adults with mild-moderate dementia are encouraged to shape innovative treatments as well as to identify possible adverse effects on participants' mood linked to scarcity of coping capabilities as source of distress in older individuals.

Background: Evidence suggests that lipoprotein metabolism play a crucial role in Alzheimer's disease (AD). However, their involvement in late-onset AD (LOAD) remains unclear.

Objective: This study aimed to uncover potential associations between lipoprotein metabolism and clinical LOAD diagnosis, cognitive function, and treatment.

Methods: We performed a lipidomic analysis of plasma samples from 46 individuals with LOAD and 16 healthy controls to investigate the potential association between lipoprotein profiles, LOAD diagnosis and cognitive function. Then, we conducted a protein-protein interaction analysis to explore the potential therapeutic role of lipoprotein molecules in LOAD.

Results: Our findings revealed that ApoA2 and HDL ApoA2 may be negatively associated with LOAD risk (odds ratio [OR] = 0.798, 95% confidence interval [CI] = 0.654-0.973, p = 0.026; OR = 0.785, 95% CI = 0.634-0.972, p = 0.026, respectively), while LDL-3 triglycerides showed a potential positive association (OR = 6.051, 95% CI = 1.789-20.470, p = 0.004). Additionally, HDL-4 ApoA1 may be positively correlated with cognitive function in LOAD (p = 0.047, r² = 0.087). Moreover, our findings suggest that ApoA2 may interact with targets of approved AD drugs.

Conclusions: This study identifies potential key lipoprotein alterations associated with LOAD diagnosis and cognitive function, emphasizing the role of lipidomic insights in understanding and treating LOAD.

Background: Three common chronic diseases in the elderly: diabetes, hypertension, and hypercholesterolemia, associate with mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Objective: We will examine the association of apolipoprotein E (APOE) ε4 allele, diabetes, hypertension, and hypercholesterolemia (in combination) with the transition of MCI to AD.

Methods: We examine patients from the National Alzheimer's Coordinating Center database from June 2005 to May 2021. AD converted from MCI, stable MCI, and non MCI/AD control subjects were analyzed using Cox proportional hazard models with propensity score weights on matching demographic information and medications prescribed at baseline.

Results: With MCI time of diagnosis as the index date, MCI patients with diabetes and hypertension carried a higher risk of developing AD (HR = 1.17, 95%CI (1.04, 1.31), p = 0.01) compared to MCI patients with a single condition. A similar observation was found among MCI patients with diabetes and hypercholesterolemia (HR = 1.20, 95%CI (1.07, 1.36), p = 0.002). Compared to MCI patients who had a single condition and without APOE ε4 allele, MCI patients with APOE ε4/4 and both diabetes and hypertension have a significantly higher risk of AD onset (HR = 7.6, 95%CI (5.02, 11.5), p < 0.0001). Those with APOE ε3/4 also have a significantly high risk (HR = 2.3, 95%CI (1.92, 2.75), p < 0.0001). Comparable outcomes were found among those with diabetes and hypercholesterolemia.

Conclusions: The combination of diabetes with hypertension or hypercholesterolemia have a significant association with the progression of MCI to AD, and APOE ε4 allele enhances the association of these selected comorbidities in promoting this conversion.

Background: The interactions between behavioral disturbances, chronic diseases, and Alzheimer's disease (AD) risk are not fully understood, particularly in the context of the COVID-19 pandemic.

Objective: This study aimed to identify key demographic, behavioral, and health-related predictors of AD using machine learning approaches.

Methods: We conducted a cross-sectional analysis of 3257 participants from the National Health and Aging Trends Study (NHATS) and its COVID-19 supplement. Predictors included demographic, behavioral, and chronic disease variables, with self-reported physician-diagnosed AD as the outcome. LASSO and random forest (RF) models identified significant predictors, and regression tree analysis examined interactions to estimate individual AD risk profiles and subgroups.

Results: Stroke, diabetes, osteoporosis, depression, and sleep disturbances emerged as key predictors of AD in both LASSO and RF models. Regression tree analysis identified three risk subgroups: a high-risk subgroup with a history of stroke and diabetes, showing a 68% AD risk among females; an intermediate-risk subgroup without stroke but with osteoporosis and positive COVID-19 status, showing a 30% risk; and a low-risk subgroup without stroke or osteoporosis, with the lowest risk (∼10%). Female patients with both stroke and diabetes had significantly higher AD risk than males (68% versus 10%, p = 0.029). Among patients without stroke but with osteoporosis, COVID-19 positivity increased AD risk by 20% (30% versus 10%, p = 0.006).

Conclusions: Machine learning effectively delineates complex AD risk profiles, highlighting the roles of vascular and metabolic comorbidities and the modifying effects of sex, osteoporosis, and COVID-19. These insights support targeted screening and early intervention strategies to improve outcomes in older adults.

Background: The presence of the apolipoprotein E4 (APOE4) allele and periodontal disease are independently correlated with higher levels of amyloid-β and inflammation in the brain, worse cognition, and Alzheimer's disease.

Objective: To assess whether the presence of the APOE4 allele modifies the relationship between IgG antibodies against periodontal microorganisms and cognitive function in older adults participating in the NHANES III study.

Methods: This cross-sectional analysis was conducted among participants of the third National Health and Nutrition Examination Survey (NHANES III) (1988 to 1994), aged 60 years and older, with measurements of IgG antibodies against 19 periodontal microorganisms and APOE4 alleles (N = 1644).

Results: Approximately 77.5% of participants carried no APOE4 allele, 20.0% had one allele, and 2.6% were homozygous. Mean cognitive scores were 16.1, 16.0, and 15.3 for non-carriers, heterozygous, and homozygous APOE4 allele carriers, respectively (p = 0.01). Antibody groups were not correlated with APOE4 carrier status. The Orange-Blue cluster (antibodies against E. nodatum, A. naeslundii) was correlated with cognitive score (Spearman r = 0.08, p < 0.001), but not other antibody groups. In the multivariable-adjusted models, APOE4 alleles did not modify the associations between antibody clusters and cognitive score (p-interaction > 0.05).

Conclusions: Mean cognitive scores were lower among APOE4 carriers. The APOE4 allele did not modify associations between groups of IgG antibodies against periodontal microorganisms and cognition among older aged adults without cognitive impairment. These findings need to be verified in larger prospective studies.