Alzheimer's & Dementia最新文献

INTRODUCTION

Various indicators of neurodegeneration (N) are used in the assessment of neuronal injury in Alzheimer's disease (AD). The heterogeneity of such indicators is less clear.

METHODS

A total of 416 individuals with different cognitive statuses were recruited for this study. Differential associations of hippocampal volume (HV), 18F-fluorodeoxyglucose positron emission tomography (FDG PET) standardized uptake value ratios (SUVRs), and plasma neurofilament light chain (NfL) levels with amyloid beta (Aβ)–tau pathology and cognitive impairment were examined.

RESULTS

HV decreased early during the high Aβ burden but tau-negative stage. FDG PET SUVRs and plasma NfL levels notably changed at tau-positive stages. HV and plasma NfL correlated with cognitive scores in the early to middle stages, while FDG PET SUVRs aligned with cognitive decline from the middle to late stages. Hippocampal atrophy and inferior parietal hypometabolism increased the risk of cognitive impairment in A+T+, while adding NfL+ had no additional impact within the distinct A/T groups.

DISCUSSION

Different indicators of N have varying relationships to AD pathology and cognitive impairment.

Highlights

INTRODUCTION

The functional study of genetic risk factors for Alzheimer's disease (AD) provides insights into the underlying mechanisms and identification of potential therapeutic targets. Investigating AD-associated genetic loci identified in East Asian populations using single-nucleus RNA-sequencing data may identify novel functional genetic contributors.

METHODS

Cell type–specific expression quantitative trait loci (eQTL) and peak-to-gene links were used to identify functional genes associated with 26 genetic loci from seven genome-wide association studies (GWAS) for AD in East Asians.

RESULTS

KCNJ6 and MAPK1IP1L were identified as significant eQTLs with AD risk loci. AD risk loci were in peaks related to four genes, with CLIC4 being connected across different cell types. Genes identified in European and East Asian GWAS interacted within networks and were enriched in AD pathology pathways in astrocytes.

DISCUSSION

Our findings suggest KCNJ6 and CLIC4 as novel AD-associated functional genes, providing insight into the genetic architecture of AD in East Asians.

Highlights

INTRODUCTION

POINTER Neurovascular (POINTER-NV) is an ancillary study that leverages the rich infrastructure and design of the U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) to investigate neurovascular mechanisms that may underlie intervention effects on key brain outcomes.

METHODS

A comprehensive neurovascular assessment is conducted at baseline, Month 12, and Month 24 using a variety of complementary non-invasive techniques including transcranial Doppler ultrasound, carotid ultrasound, echocardiography, tonometry, and continuous blood pressure and heart rate monitoring. Measurements are acquired at rest and during orthostatic challenges, hyperventilation, and carbon dioxide inhalation.

RESULTS

The primary outcomes are baroreflex sensitivity and cerebral autoregulation. Secondary outcomes include aortic, carotid, and cerebral hemodynamics and various measures of autonomic function and vascular structure and function.

DISCUSSION

POINTER-NV will provide critical insight into neurovascular mechanisms that may change with intensive lifestyle modification and promote improvements in cognition and overall brain health.

Highlights

In 2022, the World Health Organization (WHO) issued the Intersectoral Global Action Plan for Epilepsy and Other Neurological Disorders for 2022 to 2031, emphasizing important connections between brain health, population well-being, and economic growth. A year later, the WHO followed up with strategic guidelines aimed at enhancing brain health outcomes in developing countries. However, critical gaps remain. Our policy forum paper advocates for policies that target brain health across all stages of life, starting with measures to reduce the consumption of alcohol, sugar, and tobacco. Additionally, we propose the integration of school meal programs and social pension schemes as essential lifespan policies to safeguard brain health. To support these policies, developing countries must implement key macroeconomic reforms. These include revising international trade agreements, strengthening tax systems, curbing illicit financial flows, eliminating financial exclusions, and expanding social welfare systems. Such reforms are critical for creating an environment that supports long-term brain health initiatives.

Highlights

INTRODUCTION

Cognition is reduced at low and high glucose, reflecting cognitive vulnerability to glucose (CVG) fluctuations. The impact of glucose fluctuations on the aging brain remains unclear. We examined whether CVG is associated with plasma biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration.

METHODS

Participants included N = 114 adults with type 1 diabetes assessed for processing speed and sustained attention using ecological momentary assessment (EMA) combined with continuous glucose monitoring (CGM). We characterized associations between CVG and amyloid beta (Aβ) 42/40, phosphorylated tau (p-tau) 181 and 217, neurofilament light chain, and glial fibrillary acidic protein.

RESULTS

CVG was associated with all plasma biomarkers, except Aβ 42/40. CVG for sustained attention exhibited strong associations with p-tau biomarkers that persisted across covariate specifications.

DISCUSSION

CVG may be a useful digital phenotype of AD. It remains unclear whether CVG contributes to versus arises from neurodegeneration. We consider possible mechanisms linking cognitive vulnerability and long-term glucose variability to the development of neuropathology.

Highlights

INTRODUCTION

Whether prescription opioid exposure, duration, and dose are associated with cognitive function remains inconclusive.

METHODS

A longitudinal cohort among 3097 older adults with chronic pain and without dementia was conducted using Health and Retirement Study (HRS) linked to Medicare data from 2006 to 2020. Prescription opioid exposure, cumulative use for ≥ 90 days, and high-dose use (≥ 90 morphine milligram equivalents [MME] daily) were assessed biennially. Memory score and dementia probability were derived from HRS cognitive measures and analyzed using linear mixed-effects models.

RESULTS

Adjusted memory decline and dementia probability were not statistically different between patients with (vs. without) opioid exposure and between patients with cumulative use for ≥ 90 days (vs. < 90 days) but were higher between participants with high-dose opioid use (vs. low-dose) at the end of the follow-up.

DISCUSSION

Prescription opioid exposure and duration were not associated, but high-dose opioid use was associated with greater memory decline and dementia probability.

Highlights

INTRODUCTION

Limited data exist on the utility of plasma biomarkers to predict incident abnormal amyloid positron emission tomography (PET). In this study we evaluate the association of plasma Alzheimer's disease (AD) biomarkers with amyloid PET progression among initially amyloid PET negative (A−) individuals.

METHODS

We included 290 A−, cognitively unimpaired Mayo Clinic Study of Aging participants. We estimated the association of each baseline plasma biomarker with progression from A− to A+ and with rate of amyloid PET change.

RESULTS

Interquartile range differences in amyloid beta 42/40, percent phosphorylated tau 217 (%p-tau217), and Amyloid Probability Score 2 were associated with 1.29 (P = 0.09), 1.38 (P < 0.001), and 1.20 (P = 0.05) increases, respectively, in the hazard of progression from A− to A+ and 0.27 (P = 0.16), 0.50 (P = 0.007), and 0.28 (P = 0.15) Centiloid/year increases, respectively, in annual rate of amyloid PET change.

DISCUSSION

Plasma %p-tau217 may be a useful screening tool to enrich for participants with increased likelihood of progressing from normal to abnormal amyloid PET in a primary prevention trial.

Highlights