Associations of depressive symptoms with white matter abnormalities and regional cerebral blood flow in patients with amnestic mild cognitive impairment.

Aim: Depressive symptoms are one of the most common neuropsychiatric symptoms in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), although the pathophysiologies of the depressive symptoms that occur in these diseases have not been elucidated to date. In this study, we therefore investigated the associations between depressive symptoms and cognitive performance, white matter abnormalities, and regional cerebral blood flow (rCBF) in amnestic MCI patients.

Methods: Thirty-eight patients with amnestic MCI were analyzed.

Association of regional white matter hyperintensity volumes with cognitive dysfunction and vascular risk factors in patients with amnestic mild cognitive impairment.

Aim: White matter hyperintensities (WMH) obtained by magnetic resonance imaging (MRI) have been reported to promote neurodegeneration and cognitive decline in patients with mild cognitive impairment (MCI). However, little is known about the association between regional WMH (rWMH) and cognitive dysfunction in MCI. We hence investigated the associations between rWMH volumes and cognitive dysfunction in MCI.

Association of White Matter Hyperintensity Progression with Cognitive Decline in Patients with Amnestic Mild Cognitive Impairment.

Background: White matter hyperintensities (WMH) on MRI have been reported to increase the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, effects of the progression of WMH on the cognition of patients with MCI remains unclear to date.

Objective: To investigate the association between WMH progression and cognitive decline in amnestic MCI patients.

Phosphorylated TDP-43 localizes to chronic cerebral infarctions in human brains.

The transactivation response DNA-binding protein of 43 kDa (TDP-43) is a nuclear protein pivotal in RNA processing. Because phosphorylated TDP43 (pTDP-43) has been identified as a component of the ubiquitin-positive and tau-negative inclusions observed in the brains of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients, it is considered to play a major role in neurodegenerative processes. We previously reported that pTDP-43 is located in macrophages of atherosclerotic lesions of human carotid and major cerebral arteries.

Essential autophagic protein Beclin 1 localizes to atherosclerotic lesions of human carotid and major intracranial arteries.

Macrophage autophagy has been shown to exert a protective role in atherosclerosis. Beclin 1 is an essential autophagic protein, and the Beclin-1-interacting complex promotes the formation of autophagosomes. However, the localization of Beclin 1 in human atherosclerotic lesions has not been clarified to date.

Association of serum cystatin C with white matter abnormalities in patients with amnestic mild cognitive impairment.

Aim: White matter hyperintensities (WMH) on MRI have been reported to be a risk factor for the conversion from mild cognitive impairment (MCI) to Alzheimer's disease, although the reason remains unclear. In the present study, we hence investigated the associations between WMH volumes and cognitive function, blood levels of various molecules, and the presence of lifestyle-associated diseases in patients with amnestic MCI.

Methods: The initial data of 38 patients with amnestic MCI and 10 normal control individuals were analyzed.

Frontotemporal dementia-associated protein "phosphorylated TDP-43" localizes to atherosclerotic lesions of human carotid and main cerebral arteries.

The transactivation response DNA binding protein (TARDP) of 43 kDa (TDP-43) is a nuclear protein pivotal in RNA processing. Because phosphorylated (p) TDP-43 has been identified as a component of ubiquitin-positive and tau-negative inclusions in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), it is considered to play a major role in neurodegenerative processes. We investigated the immunolocalization of pTDP-43 in atherosclerotic lesions of human carotid and main cerebral arteries.

Neuroimaging Characteristics of Frailty Status in Patients with Alzheimer's Disease.

Background/objective: Although frailty is closely linked to dementia, particularly Alzheimer's disease (AD), underlying pathophysiology of frailty associated with AD remains uncertain. This study aimed to investigate differences in structural and functional brain imaging abnormalities between AD with and without frailty.

Methods: A total of 191 outpatients with probable AD (men: 91; women: 100; age: 80.

Caregivers' education decreases depression symptoms and burden in caregivers of patients with dementia.

Objective: To determine whether providing education to caregivers of patients with dementia decreases their depression symptoms and burden.

Methods: Eighty-three outpatients with dementia being treated at the Memory Clinic of Tokyo Medical University Hospital and their caregivers were enrolled. Forty-seven caregivers were enrolled in the caregivers' education (EDU) group and 36 were enrolled in the control (CTL) group.

Amyloid and Tau Positron Emission Tomography in Suggested Diabetesrelated Dementia.

Background: Type 2 diabetes mellitus (DM) has been shown to increase the risk for cognitive decline and dementia, such as Alzheimer disease (AD) and vascular dementia (VaD). In addition to AD and VaD, there may be a dementia subgroup associated with specific DM-related metabolic abnormalities rather than AD pathology or cerebrovascular disease, referred to as diabetes-related dementia (DrD).

Method: We studied 11C-PiB and 11C-PBB3 positron emission tomography (PET) in 31 subjects with DrD and 5 subjects with AD associated with DM to assess amyloid and tau deposits in the brain.

14-3-3 protein sigma isoform co-localizes with phosphorylated α-synuclein in Lewy bodies and Lewy neurites in patients with Lewy body disease.

α-Synuclein shares structural homology with 14-3-3 proteins. Seven 14-3-3 protein isoforms have been identified in mammals. Among them, the 14-3-3 sigma isoform was initially considered absent in the mammalian brain.

Time-dependent and lesion-dependent HMGB1-selective localization in brains of patients with cerebrovascular diseases.

High mobility group box 1 protein (HMGB1) has multiple functions, including the maintenance of nucleosomes and the regulation of gene transcription. HMGB1 is released from activated macrophages, resulting in the induction of inflammatory cytokines. Recently, much research about the role of HMGB1 in cerebrovascular disease (CVD) has been reported.

Calmodulin-like skin protein is downregulated in human cerebrospinal fluids of Alzheimer's disease patients with apolipoprotein E4; a pilot study using postmortem samples.

Objective: Calmodulin-like skin protein (CLSP) is a secreted peptide that inhibits neuronal cell death, linked to Alzheimer's disease (AD), by binding to the heterotrimeric humanin receptor and activating an intracellular survival pathway. CLSP is only expressed in skin keratinocytes and related epithelial cells, circulates in the blood stream, and passes the blood-cerebrospinal fluid (CSF) barrier. In the current study, we addressed the issues as to whether CLSP functions in the central nervous system and whether the concentration of CLSP is reduced in the CSFs of AD patients.

Correlation between clinical symptoms and striatal DAT uptake in patients with DLB.

Objective: It is widely known that there is low striatal I-FP-CIT dopamine transporter-single photon emission tomography (DAT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). We assessed the correlation between symptom and regional low DAT uptake in the striatum.

Methods: Patients with Alzheimer's disease (AD) (n = 95) and patients with DLB (n = 133) who underwent DAT-SPECT were enrolled.

14-3-3 eta isoform colocalizes TDP-43 on the coarse granules in the anterior horn cells of patients with sporadic amyotrophic lateral sclerosis.

The immunolocalization of the 14-3-3 eta isoform in the anterior horn cells (AHCs) of patients with sporadic amyotrophic lateral sclerosis (ALS) and controls was examined. Compared with the immunolocalization of other 14-3-3 isoforms, the immunolocalization of the 14-3-3 eta isoform was either synaptic at the periphery of AHCs, spindle-shaped in neurites, or granular in the cytoplasm. By double labeling with phosphorylated (p-)TDP-43, the transactivation response DNA binding protein of 43kDa (TDP-43) demonstrated frequent colocalization of the 14-3-3 eta isoform in granular structures (90%) and spindle-shaped structures (85.

Neuroimaging for diagnosing dementia with Lewy bodies: What is the best neuroimaging technique in discriminating dementia with Lewy bodies from Alzheimer's disease?

Aim: We compared the diagnostic value of four neuroimaging techniques, namely, I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ( I-FP-CIT) dopamine transporter single-photon emission computed tomography (DAT-SPECT), magnetic resonance imaging, perfusion SPECT and I-metaiodobenzyl-guanidine myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD).

Methods: A total of 32 patients with probable AD and 32 patients with probable DLB were enrolled in the present study. For the comparison study, we used the specific binding ratio for DAT-SPECT, the heart-to-mediastinum ratio in the delay phase for I-metaiodobenzyl-guanidine myocardial scintigraphy, z-scores in the medial occipital lobe for perfusion SPECT and z-scores of hippocampal atrophy using a voxel-based specific regional analysis system for AD for magnetic resonance imaging.

Utility of the combination of DAT SPECT and MIBG myocardial scintigraphy in differentiating dementia with Lewy bodies from Alzheimer's disease.

Purpose: (123)I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT SPECT) and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy can be used to assist in the diagnosis of patients with dementia with Lewy bodies (DLB). We compared the diagnostic value of these two methods in differentiating DLB from Alzheimer's disease (AD). Furthermore, we evaluated whether a combination of DAT SPECT and MIBG myocardial scintigraphy would provide a more useful means of differentiating between DLB and AD.

[Age-related changes of sensory system].

Pathological processes usually superimpose on physiological aging even in the sensory system including visual, hearing, olfactory, taste and somatosensory functions. Representative changes of age-related changes are presbyopia, cataracts, and presbyacusis. Reduced sense of smell is seen in normal aging, but the prominent reduction detected by the odor stick identification test is noticed especially in early stage of Alzheimer or Parkinson disease.