Alzheimer's & Dementia最新文献

INTRODUCTION

Factors influencing plasma Alzheimer's disease (AD) biomarkers remain incompletely understood. Here we evaluated Fujirebio plasma p-Tau₂₁₇ in two diverse cohorts among whom 91% underwent cerebrospinal fluid (CSF) analysis.

METHODS

Non-Hispanic White (NHW, n = 113), Black/African American (B/AA, n = 66), and Chinese American (ChA, n = 38) participants recruited from two universities were included. We examined if plasma p-Tau₂₁₇ correlated with CSF and clinical factors, differed between racial groups, and associated with novel CSF proteins.

RESULTS

CSF p-Tau₁₈₁ strongly correlated with CSF p-Tau₂₁₇ (R² = 0.912) which moderately correlated with plasma p-Tau₂₁₇ (R² = 0.694). Plasma p-Tau₂₁₇ levels were higher with greater cognitive impairment but lower in B/AA than NHW participants even after adjusting for CSF p-Tau₁₈₁. This resulted in greater positive predictive value for NHW than B/AA participants, and could be mediated by complement or lysosomal pathways.

DISCUSSION

Severity of cognitive impairment and race both influence plasma p-Tau₂₁₇ levels beyond race-associated differences in CSF p-Tau₁₈₁.

Highlights

INTRODUCTION

Positron emission tomography (PET) imaging studies have shown that amyloid beta (Aβ) is significantly correlated with glucose metabolism in mild cognitive impairment independently of the apolipoprotein E (APOE) ε4 genotype.

METHODS

We used a singular value decomposition (SVD) approach to pairwise cross-correlation among tau, Aβ, and fluorodeoxyglucose PET images. The resulting SVD-based tau and Aβ scores as well as the APOE ε4 genotype, were entered as predictors in a voxelwise general linear model for statistical assessment of their effect on FDG.

RESULTS

We found cortical regions where a reduced glucose metabolism was maximally correlated with distributed patterns of tau, accounting for the effect of Aβ and APOE ε4 genotype.

DISCUSSION

By highlighting the more significant role of tau, rather than Aβ, in the reduction of glucose metabolism, our results provide a better understanding of their combined effect in the development and progression of Alzheimer's disease.

Highlights

INTRODUCTION

The long-term implications of disclosing Alzheimer's disease (AD) biomarker information to cognitively unimpaired individuals are unknown.

METHODS

We compared participants who disclosed their elevated amyloid imaging result in a preclinical AD trial to those who disclosed a not elevated result and enrolled in an observational cohort that underwent parallel assessments. Our primary outcome was a score > 0 on the Columbia Suicidality Severity Rating Scale (CSSRS) at any visit; we also considered suicidal behaviors (CSSRS > 5).

RESULTS

Among 1707 total participants (68% elevated amyloid, mean [standard deviation] age 71.5 [4.7], 60% female, 90% non-Hispanic White), followed for a mean 218 (74.1) weeks, there were no suicides and few indications of suicidal thoughts (n = 124 [7%]) or behaviors (n = 13 [<1%]). In a generalized estimating equation model controlling for covariates, we observed no effect of amyloid status on the primary outcome of CSSRS > 0 (odds ratio = 1.6, 95% confidence interval = 0.76, 3.37).

DISCUSSION

With a structured approach, brain amyloid results can be returned safely.

Highlights

INTRODUCTION

Foundational models suggest Alzheimer's disease (AD) can be diagnosed using retinal images, but the specific structural features remain poorly understood. This study investigates retinal vascular changes in individuals with cognitive impairment in three East Asian regions.

METHODS

A multicenter study was conducted in Shanghai, Hong Kong, and Ningxia, collecting retinal images from 176 patients with mild cognitive impairment (MCI) or AD and 264 controls. The VC-Net deep learning model segmented arterial/venous networks, extracting 36 vascular features.

RESULTS

Significant reductions in vessel length, segment number, and vascular density were observed in cognitively impaired patients, while venous structure and complexity were correlated with the level of cognitive function.

DISCUSSION

Retinal vascular changes may serve as indicators of cognitive impairment, requiring validation in larger cohorts and exploration of the underlying mechanisms.

Highlights

INTRODUCTION

Physical activity is associated with greater myelin content in older individuals with cerebral small vessel disease (CSVD), a condition marked by demyelination. However, potential mechanisms underlying this relationship remain understudied.

METHODS

We assessed cross-sectionally whether serum high-density lipoprotein (HDL), low-density lipoprotein, and triglycerides moderated the association between physical activity and in vivo myelin in older individuals with CSVD and mild cognitive impairment.

RESULTS

We included 81 highly educated, community-dwelling older individuals (mean age 74.57 years), 64% of whom were female. Regression models revealed that HDL levels significantly moderated the relationship between physical activity and myelin in the sagittal stratum, wherein higher physical activity levels were linked to greater myelin levels for those with average or high HDL (standardized B [95% CI] = 0.289 [0.087 to 0.491], p = 0.006).

DISCUSSION

Physical activity may promote myelin health partly through HDL. Data from longitudinal studies are needed to confirm our findings.

Highlights

INTRODUCTION

Apolipoprotein E (APOE) ε4 allele status is associated with an increased risk of Alzheimer's disease and should be determined prior to initiation of anti-amyloid beta antibody treatment, because of increased risk of treatment-related side effects. Plasma-based apoE4 proteotyping may be an alternative to genotyping, with limited clinical evidence.

METHODS

apoE4 proteotyping was performed on 164 memory-clinic patients, using one chemiluminescent enzyme immunoassay (CLEIA) and one nucleic acid–linked immunosandwich assay (NULISA). The assays were evaluated against APOE ε4 blood genotyping.

RESULTS

The CLEIA had a 100% sensitivity and 98.5% specificity to classify APOE ε4 homozygosity and carriership in relation to genotyping. The NULISA had a 92.9% sensitivity and 97.1% specificity to classify homozygosity and a 100% sensitivity and 98.5% specificity to classify carriership.

DISCUSSION

The high performance suggests that the assays may be used as an easily available tool for identifying individuals for definitive APOE ε4 genotyping in a two-step approach.

Highlights

INTRODUCTION

Neuronal intranuclear inclusion disease (NIID) manifests as dementia combined with other neurological symptoms. However, small fiber neuropathy (SFN) and pathology remain unknown in NIID.

METHODS

A total of 294 subjects, including patients with NIID, Parkinson's disease, Alzheimer's disease, diabetic peripheral neuropathy, and healthy controls (HCs), were included. Clinical scales, sensory and autonomic function testing, and skin biopsy were performed.

RESULTS

NIID patients had more severe sensory and autonomic dysfunction than other groups. Substantial reductions in intraepidermal, sweat gland, and pilomotor nerve fiber densities were observed in NIID patients, with a non–length dependent pattern. Detailed analysis revealed marked reductions in noradrenergic, cholinergic, peptidergic, and regenerative nerve fibers. Small fiber densities showed high diagnostic accuracy in distinguishing NIID from HCs and other diseases.

DISCUSSION

This study is the first to reveal wide and severe loss of small fibers in NIID, suggesting the involvement of SFN in the pathogenesis of NIID.

Highlights

INTRODUCTION

We investigated the moderating effects of midlife and late-life cognitive activity (CA) on the relationship between tau pathology and both cognition and cognitive decline.

METHODS

Eighty-nine non-demented older adults from a Korean cohort underwent comprehensive evaluations, including CA assessments and tau neuroimaging at baseline, and Mini-Mental State Examination (MMSE) at baseline and the 2-year follow-up.

RESULTS

Greater midlife CA was associated with higher MMSE scores in a given amount of tau pathology, whereas higher levels of midlife CA were associated with faster tau-related decline in MMSE scores, particularly in individuals with mild cognitive impairment. Late-life CA did not exhibit any interaction with tau on either MMSE scores or their 2-year change.

DISCUSSION

Greater midlife CA is generally associated with better cognitive performance despite the presence of tau pathology. However, paradoxically, increased midlife CA appears to be linked to a more rapid tau-related cognitive decline in already cognitively impaired individuals.

Highlights

INTRODUCTION

Early symptoms in young onset Alzheimer's disease (YOAD) may be misinterpreted, causing delayed diagnosis. This population-based study aimed to map adverse occupational events preceding YOAD diagnosis as potential prodromal signs.

METHODS

In a register-based, incidence density matched nested case-control study, we examined unemployment and long-term sick leave among individuals diagnosed with YOAD in Danish memory clinics between 2016 and 2022 compared to controls over a 13-year period. Conditional logistic regression produced incidence rate ratios (IRRs).

RESULTS

The study included 2434 cases and 12,170 controls. YOAD patients had higher rates of adverse occupational events, particularly long-term sick leave, starting from 8 years before diagnosis (IRR 1.40, 95% confidence interval [CI] 1.07–1.84) and increasing to an IRR of 29.59 (95% CI 18.97–46.13) in the year before diagnosis.

DISCUSSION

Adverse occupational events may serve as warning signs of YOAD. Timely diagnosis could facilitate restructuring the remaining working life to accommodate cognitive deficits or in seeking a disability pension.

HIGHLIGHTS

INTRODUCTION

Dual cognitive and mobility decline is more strongly associated with dementia risk than cognitive decline only. It remains unknown whether this syndrome is associated with brain atrophy patterns, white matter (WM) damage, or pathology.

METHODS

In the Baltimore Longitudinal Study of Aging participants with and without dual decline, we used linear mixed-effects models to compare up to 13-year longitudinal changes in MRI-derived atrophy patterns, WM hyperintensities (n = 339), microstructure (n = 307), plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid beta 42/40 (Aβ_42/40) ratio (n = 349), and phosphorylated tau 181 (pTau181) (n = 258).

RESULTS

Those experiencing dual decline showed accelerated atrophy in medial temporal (p = .004), parietotemporal (p = .029), and perisylvian regions (p = .028), whereas gait decline only showed accelerated parietotemporal atrophy (p = .035) and memory decline only showed perisylvian atrophy (p = .021). Dual decline was also associated with unique microstructural deterioration in several WM tracts (p < .05), a greater decrease in Aβ_42/40 ratio (p = .015), and greater increases in GFAP (p = .009) and NfL (p < .001).

DISCUSSION

Individuals experiencing dual decline are at an increased risk for regional brain atrophy, microstructural degradation, and biomarker-defined molecular changes underlying dementia.

Highlights