September 13, 2016

new issue of - American Journal of Alzheimer's Disease & Other Dementias

Table of Contents

August 2016; 31 (5)

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A Systematic Review of Metacognitive Differences Between Alzheimer’s Disease and Frontotemporal Dementia

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 381-388,

Clinicians often have difficulty distinguishing between various forms of dementia to achieve a correct diagnosis. Little research has been done to examine whether awareness of one’s cognitive deficits, or metacognitive monitoring, might differ between dementia diagnoses, thereby providing an additional means of differentiating between dementia subtypes. We review articles examining metacognitive comparisons between two of the most common dementia subtypes: Alzheimer’s disease and frontotemporal dementia. Greater monitoring deficits were apparent in frontotemporal dementia than in Alzheimer’s disease, and participants with frontotemporal dementia were less likely to utilize task experience to update and improve the accuracy of subsequent monitoring judgments. Results provide evidence for the utility of metacognitive measures as a means of distinguishing between Alzheimer’s disease and frontotemporal dementia.

Current Topics in Research


Association of Dementia and Peptic Ulcer Disease: A Nationwide Population-Based Study

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 389-394,

Objective: We determine the association between dementia and the subsequent peptic ulcer disease (PUD).

Methods: We identified patients with diagnosed dementia in the Taiwan National Health Insurance Research Database. A comparison cohort without dementia was frequency-matched by age, sex, and comorbidities, and the occurrence of PUD was evaluated in both cohorts.

Results: The dementia and control cohort consisted of 6014 patients with dementia and 17 830 frequency-matched patients without dementia, respectively. The incidence of PUD (hazard ratio, 1.27; 95% confidence interval, 1.18-1.37; P < .001) was higher among patients with dementia. Cox models showed that being female, diabetes mellitus, chronic kidney disease, coronary artery disease, and chronic obstructive pulmonary disease were independent risk factors for PUD in patients with dementia.

Conclusion: Dementia might increase the risk of developing PUD.


Use of Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and Risk of Dementia in Heart Failure

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 395-404,

Objective: To test the effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) on reducing the risk of dementia in patients with heart failure (HF).

Methods: This retrospective, longitudinal study used a cohort of HF patients identified from a local Medicare advantage prescription drug plan. Multivariable time-dependent Cox model and marginal structural model using inverse-probability-oftreatment weighting were used to estimate the risk of developing dementia. Adjusted dementia rate ratios were estimated among current and former ACEI/ARB users, as compared with nonusers.

Results: Using the time-dependent Cox model, the adjusted dementia rate ratios (95% confidence-interval) among current and former users were 0.90(0.70-1.16) and 0.89 (0.71-1.10), respectively. Use of marginal structural model resulted in similar effect estimates for current and former users as compared with the nonusers.

Conclusion: This study found no difference in risk of dementia among the current and former users of ACEI/ARB as compared with the nonusers in an already at-risk HF population.


Toxicological Differences Between NMDA Receptor Antagonists and Cholinesterase Inhibitors

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 405-412,

Cholinesterase inhibitors (ChEIs), represented by donepezil, rivastigmine, and galantamine, used to be the only approved class of drugs for the treatment of Alzheimer’s disease. After the approval of memantine by the Food and Drug Administration (FDA), N-methyl-d-aspartic acid (NMDA) receptor antagonists have been recognized by authorities and broadly used in the treatment of Alzheimer’s disease. Along with complementary mechanisms of action, NMDA antagonists and ChEIs differ not only in therapeutic effects but also in adverse reactions, which is an important consideration in clinical drug use. And the number of patients using NMDA antagonists and ChEIs concomitantly has increased, making the matter more complicated. Here we used the FDA Adverse Event Reporting System for statistical analysis , in order to compare the adverse events of memantine and ChEIs. In general, the clinical evidence confirmed the safety advantages of memantine over ChEIs, reiterating the precautions of clinical drug use and the future direction of antidementia drug development.


Tong Luo Jiu Nao, a Chinese Medicine Formula, Reduces Inflammatory Stress in a Mouse Model of Alzheimer’s Disease

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 413-421, Abstract

Aim: The aim of this study is to extend the molecular mechanism of Tong Luo Jiu Nao (TLJN) for Alzheimer’s disease (AD), which is a modern Chinese formula that has been used to treat AD.

Methods: The senescence-accelerated mouse prone 8 strain (SAMP8) is one of the most appropriate models to study the mechanism that underlies AD. The levels of plasma amyloid β (Aβ) and the Aβ deposits were measured using enzyme-linked immunosorbent assay and immunohistochemistry. Immunoblotting was used to observe the effect of TLJN on inflammatory mediator expression in an senescence-accelerated mouse model of AD.

Results: Our data showed that the TLJN-treated groups exhibited a reduction in plasma Aβ levels and reduced Aβ expression. Moreover, TLJN effectively attenuated Aβ-induced activation of extracellular signal-regulated kinase and c-Jun N-terminal kinases and blocked changes in inflammatory mediator expression.

Conclusion: These data suggest that TLJN might have protective effects and could potentially act to attenuate inflammatory stress in the pathogenesis of AD.


Hydrogen Proton Magnetic Resonance Spectroscopy in Multidomain Amnestic Mild Cognitive Impairment and Vascular Cognitive Impairment Without Dementia

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 422-429, To investigate the value of hydrogen proton magnet resonance spectroscopy (1H-MRS) in the differential diagnosis of multiple-domain amnestic mild cognitive impairment (M-aMCI) and vascular cognitive impairment with no dementia (VCIND); 1H-MRS was performed in patients with M-aMCI and VCIND. The level was determined for N-acetylaspartate (NAA), glutamate (Glu), inositol (mI), choline (Cho), and creatine (Cr). Compared with the normal control group, the NAA–Cr ratio in all regions studied was significantly lower in the M-aMCI and VCIND groups. The Glu–Cr ratio in the posterior cingulate gyrus of the M-aMCI group was significantly lower than in the VCIND. The mI–Cr ratio in the frontal white matter of the VCIND was significantly higher than in the M-aMCI group. In the white matter adjacent to the lateral ventricles, the Cho–Cr ratio was significantly higher in the VCIND than the M-aMCI. Our results suggested 1H-MRS is an effective method in the differential diagnosis of M-aMCI and VCIND.


Retinal Nerve Fiber Layer Thinning in Alzheimer’s Disease: A Case–Control Study in Comparison to Normal Aging, Parkinson’s Disease, and Non-Alzheimer’s Dementia

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 430-436,

Retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness, and macular volume (MV) utilizing spectral domain optical coherence tomography (SD-OCT) were compared among patients with Alzheimer’s disease (AD) dementia, non-Alzheimer’s disease (non-AD) dementia, amnestic mild cognitive impairment (aMCI), Parkinson’s disease (PD), and age- and sex-matched controls in a cross-sectional cohort study. A total of 116 participants were diagnosed and evaluated (21 AD, 20 aMCI, 20 non-AD, 20 PD, and 34 controls) after comprehensive neurological, neuropsychology, and magnetic resonance imaging (MRI) volumetric evaluations. Retinal nerve fiber layer thickness, GCL thickness, and MV were measured. Analysis of variance models were used to compare groups on MRI volumetric measures, cognitive test results, and SD-OCT measures. Associations between SD-OCT measures and other measures were performed using mixed-effect models. Spectral domain optical coherence tomography analysis of retinal markers, including RNFL thickness, GCL thickness, and MV, did not differ between amnestic MCI, AD dementia, PD, non-AD, dementia, and age- and sex-matched controls in a well-characterized patient cohort.

Vascular Function in Alzheimer’s Disease and Vascular Dementia

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 437-442,

o    We investigated vascular functioning in patients with a clinical and radiological diagnosis of either Alzheimer’s disease (AD) or vascular dementia (VaD) and examined a possible relationship between vascular function and cognitive status. Twenty-seven patients with AD, 23 patients with VaD, and 26 healthy control patients underwent measurements of flow-mediated dilation (FMD), ankle–brachial index (ABI), cardioankle vascular index (CAVI), and intima–media thickness (IMT). The FMD was significantly lower in patients with AD or VaD compared to controls. There were no significant differences in ABI, CAVI, or IMT among the 3 groups. A significant correlation was found between Mini-Mental State Examination (MMSE) scores and FMD. Furthermore, a multiple regression analysis revealed that FMD was significantly predicted by MMSE scores. These results suggest that endothelial involvement plays a role in AD pathogenesis, and FMD may be more sensitive than other surrogate methods (ABI, CAVI, and IMT) for detecting early-stage atherosclerosis and/or cognitive decline.


Cognitive Reserve in Healthy Aging and Alzheimer’s Disease: A Meta-Analysis of fMRI Studies

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 443-449,

Cognitive reserve (CR) has been defined as the ability to optimize or maximize performance through differential recruitment of brain networks. In the present study, we aimed at providing evidence for a consistent brain network underpinning CR in healthy and pathological aging. To pursue this aim, we performed a coordinate-based meta-analysis of 17 functional magnetic resonance imaging studies on CR proxies in healthy aging, Alzheimer’s disease (AD), and mild cognitive impairment (MCI). We found that different brain areas were associated with CR proxies in healthy and pathological aging. A wide network of areas, including medial and lateral frontal areas, that is, anterior cingulate cortex and dorsolateral prefrontal cortex, as well as precuneus, was associated with proxies of CR in healthy elderly patients. The CR proxies in patients with AD and amnesic-MCI were associated with activation in the anterior cingulate cortex. These results were discussed hypothesizing the existence of possible compensatory mechanisms in healthy and pathological aging.


Family History of Alzheimer’s Disease and Cortical Thickness in Patients With Dementia

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 450-456,

A first-degree family history of Alzheimer’s disease reflects genetic risks for the neurodegenerative disorder. Recent imaging data suggest localized effects of genetic risks on brain structure in healthy people. It is unknown whether this association can also be found in patients who already have dementia. Our aim was to investigate whether family history risk modulates regional medial temporal lobe cortical thickness in patients with Alzheimer’s disease. We performed high-resolution magnetic resonance imaging and cortical unfolding data analysis on 54 patients and 53 nondemented individuals. A first-degree family history of Alzheimer’s disease was associated with left hemispheric cortical thinning in the subiculum among patients and controls. The contribution of Alzheimer’s disease family history to regional brain anatomy changes independent of cognitive impairment may reflect genetic risks that modulate onset and clinical course of the disease.

Opinions and Controversies

Relation of Poor Memory to Soluble Tumor Necrosis Factor Receptor Type Two (sTNF-RII)

AM J ALZHEIMERS DIS OTHER DEMEN August 2016 31: 457-458,

The association of soluble tumor necrosis factor receptor type two with poor memory in patients with breast cancer and controls found by Patel et al (2015) may confirm the finding of Holmes et al in 2009 that tumor necrosis factor α is linked to cognitive decline.


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