Lecanemab-Associated Amyloid-β Protofibril in Cerebrospinal Fluid Correlates with Biomarkers of Neurodegeneration in Alzheimer's Disease.

Objective: The Clarity AD phase III trial showed that lecanemab reduced amyloid markers in early Alzheimer's disease (AD) and resulted in less decline on measures of cognition and function than placebo. Herein, we aimed to characterize amyloid-β (Aβ) protofibril (PF) captured by lecanemab in human cerebrospinal fluid (CSF) from living participants with different stages in AD, which enable an enhanced understanding of the dynamic changes of lecanemab-associated Aβ-PF (Lec-PF) in vivo.

Methods: We newly developed a unique and highly sensitive immunoassay method using lecanemab that selectively captures Lec-PF.

Magnetoencephalographic brain activity evoked by the optic-flow task is correlated with β-amyloid burden and parahippocampal atrophy.

Visuospatial perception is often impaired in people with Alzheimer's disease (AD). Because visuospatial information is thought to be processed in the visual dorsal stream, it is believed that brain activities in the dorsal stream will be altered in AD patients. In this study, we investigated whether regional brain activity related to visuospatial perception were associated with AD progression markers.

Sympathetic I-metaiodobenzylguanidine index for Lewy body disease: probability-based diagnosis and identifying patients exempt from late imaging.

Objective: We aimed to establish a practical diagnostic index for Lewy body diseases (LBD), such as Parkinson's disease and dementia, with Lewy bodies in outpatient settings and criteria for exempting patients from late imaging.

Methods: We acquired early and late I-metaiodobenzylguanidine (MIBG) images from 108 consecutive patients with suspected LBD and standardized heart-to-mediastinum (H/M) ratios for collimator conditions. Exclusions included young-onset Parkinson's disease (age < 50 years) and genetic transthyretin-type amyloidosis.

Absolute quantitation of sympathetic nerve activity using [I] metaiodobenzylguanidine SPECT-CT in neurology.

Background And Purpose: The ability of [I]metaiodobenzylguanidine (MIBG) sympathetic nerve imaging with three-dimensional (3D) quantitation to clinically diagnose neurological disorders has not been evaluated. This study compared absolute heart counts calculated as mean standardized uptake values (SUV) using conventional planar imaging and assessed the contribution of [I]MIBG single-photon emission computed tomography (SPECT)-CT to the diagnosis of neurological diseases.

Methods: Seventy-two patients with neurological diseases were consecutively assessed using early and delayed [I]MIBG SPECT-CT and planar imaging.

Transthyretin amyloid cardiomyopathy disease burden quantified using Tc-pyrophosphate SPECT/CT: volumetric parameters versus SUVmax ratio at 1 and 3 hours.

Background: Various parameters derived from technetium-99m pyrophosphate (Tc-PYP) single-photon emission computed tomography (SPECT) correlate with the severity of transthyretin amyloid cardiomyopathy (ATTR-CM). However, the optimal metrics and image acquisition timing required to quantify the disease burden remain uncertain.

Methods And Results: We retrospectively evaluated Tc-PYP SPECT/CT images of 23 patients diagnosed with ATTR-CM using endomyocardial biopsies and/or gene tests.

Exercise program to reduce the risk of cognitive decline and physical frailty in older adults: study protocol for an open label double-arm clinical trial.

Objective: It is a big problem that many older adults are physically inactive. Well-known benefits of physical exercise include a decrease in the risk of cognitive decline and physical frailty. Therefore, this study aims to examine whether our proposed exercise program can prevent cognitive decline and improve physical function in the elderly.

Effects of Melissa officinalis Extract Containing Rosmarinic Acid on Cognition in Older Adults Without Dementia: A Randomized Controlled Trial.

Background: Previous in vitro and in vivo studies on Alzheimer's disease (AD) models have reported that rosmarinic acid (RA) can inhibit the formation of amyloid-β fibrils as well as the oligomerization and deposition of amyloid-β protein. Melissa officinalis (M. officinalis) extract containing 500 mg of RA is tolerable and safe in healthy individuals and patients with mild AD dementia.

Diagnosis of Parkinson syndrome and Lewy-body disease using I-ioflupane images and a model with image features based on machine learning.

Objectives: I-ioflupane has been clinically applied to dopamine transporter imaging and visual interpretation assisted by region-of-interest (ROI)-based parameters. We aimed to build a multivariable model incorporating machine learning (ML) that could accurately differentiate abnormal profiles on I-ioflupane images and diagnose Parkinson syndrome or disease and dementia with Lewy bodies (PS/PD/DLB).

Methods: We assessed I-ioflupane images from 239 patients with suspected neurodegenerative diseases or dementia and classified them as having PS/PD/DLB or non-PS/PD/DLB.

Deterioration after Liver Transplantation and Transthyretin Stabilizer Administration in a Patient with ATTRv Amyloidosis with a Leu58Arg (p.Leu78Arg) TTR Variant.

We herein report a 44-year-old Japanese man with hereditary transthyretin amyloidosis (ATTRv amyloidosis) harboring the variant Leu58Arg (p.Leu78Arg) in TTR in whom we conducted an observational study with liver transplantation (LT) and transthyretin (TTR) stabilizers (tafamidis and diflunisal) for 9 years. This patient showed gradual deterioration of sensory, motor, and autonomic neuropathy symptoms after LT.

Volumetric evaluation of Tc-pyrophosphate SPECT/CT for transthyretin cardiac amyloidosis: Methodology and correlation with cardiac functional parameters.

Background: Volumetric evaluation of Technetium-pyrophosphate (Tc-PYP) SPECT/CT is a useful method for assessing transthyretin cardiac amyloidosis (ATTR-CA). We investigated the methodology and assessed its relationship with conventional parameters.

Methods And Results: We retrospectively evaluated Tc-PYP SPECT/CT scans of 25 patients who underwent endomyocardial biopsy and/or gene testing.

MEG activity of the dorsolateral prefrontal cortex during optic flow stimulations detects mild cognitive impairment due to Alzheimer's disease.

Dorsal stream, which has a neuronal connection with dorsolateral prefrontal cortex (DLPFC), is known to be responsible for detection of motion including optic flow perception. Using magnetoencephalography (MEG), this study aimed to examine neural responses to optic flow stimuli with looming motion in the DLPFC in patients with mild cognitive impairment due to Alzheimer's disease (AD-MCI) compared with cognitively unimpaired participants (CU). We analyzed the neural responses by evaluating maximum source-localized power for the AD-MCI group (n = 11) and CU (n = 20), focusing on six regions of interest (ROIs) that form the DLPFC: right and left dorsal Brodmann area 9/46 (A9/46d), Brodmann area 46 (A46) and ventral Brodmann area 9/46 (A9/46v).

Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer's disease progression.

We conducted a randomized placebo-controlled double-blind 24-week trial using Melissa officinalis (M. officinalis) extract richly containing rosmarinic acid (RA) on patients with mild dementia due to Alzheimer's disease (AD) with the aim to examine the safety and tolerability (primary endpoint) of RA (500 mg daily) and its clinical effects and disease-related biomarker changes (secondary endpoints). Patients (n = 23) diagnosed with mild dementia due to probable AD were randomized to either the placebo or M.

Diagnostic Criteria for Dementia with Lewy Bodies: Updates and Future Directions.

The aim of this article is to describe the 2017 revised consensus criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) with future directions for the diagnostic criteria. The criteria for the clinical diagnosis of probable and possible DLB were first published as the first consensus report in 1996 and were revised in the third consensus report in 2005. After discussion at the International DLB Conference in Fort Lauderdale, Florida, USA, in 2015, the International DLB Consortium published the fourth consensus report including the revised consensus criteria in 2017.

Long spinal cord lesions in a patient with pathologically proven multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We report the case of a 50-year-old man who presented with progressive gait ataxia. Brain magnetic resonance imaging (MRI) on fluid-attenuated inversion recovery revealed a hyperintense lesion in the right temporal white matter.

Cerebral Amyloid Angiopathy-Related Microbleeds and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease.

Background: Alzheimer's disease (AD) commonly accompanies cerebral amyloid angiopathy (CAA).

Objective: We aimed to reveal associations between CAA-related brain microbleeds and cerebrospinal fluid (CSF) markers in AD patients.

Methods: Patients with probable AD (n = 88) from consecutive patients in our memory clinic were evaluated for patient demographics, vascular risk factors, neuropsychological tests, apolipoprotein E phenotype, MRI including T2*-weighted image and fluid attenuated inversion recovery sequence, and CSF amyloid and tau markers.

Creutzfeldt-Jakob disease associated with a V203I homozygous mutation in the prion protein gene.

We report a Japanese patient with Creutzfeldt-Jakob disease (CJD) with a V203I homozygous mutation of the prion protein gene (PRNP). A 73-year-old woman developed rapidly progressive gait disturbance and cognitive dysfunction. Four months after the onset, she entered a state of an akinetic mutism.

Efficacy of diflunisal on autonomic dysfunction of late-onset familial amyloid polyneuropathy (TTR Val30Met) in a Japanese endemic area.

Objective: To evaluate the long-term efficacy and safety of diflunisal in late-onset familial amyloid polyneuropathy (FAP) in a Japanese endemic area.

Methods: Consecutive six FAP patients (mean age: 65.8 ± 7.