Journal of Alzheimer's Disease - Volume 78, issue 3

Authors: Duggan, Michael R. | Torkzaban, Bahareh | Ahooyi, Taha Mohseni | Khalili, Kamel

Article Type: Review Article

Abstract: Across the fields of virology and neuroscience, the role of neurotropic viruses in Alzheimer’s disease (AD) has received renewed enthusiasm, with a particular focus on human herpesviruses (HHVs). Recent genomic analyses of brain tissue collections and investigations of the antimicrobial responses of amyloid-β do not exclude a role of HHVs in contributing to or accelerating AD pathogenesis. Due to continued expansion in our aging cohort and the lack of effective treatments for AD, this composition examines a potential neuroviral theory of AD in light of these recent data. Consideration reveals a possible viral “Hit-and-Run” scenario of AD, as well as …neurobiological mechanisms (i.e., neuroinflammation, protein quality control, oxidative stress) that may increase risk for AD following neurotropic infection. Although limitations exist, this theoretical framework reveals several novel therapeutic targets that may prove efficacious in AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, autophagy, herpesviruses, neuroinflammation

DOI: 10.3233/JAD-200814

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 855-869, 2020

Authors: Kritikos, Minos | Gandy, Samuel E. | Meliker, Jaymie R. | Luft, Benjamin J. | Clouston, Sean A.P.

Article Type: Review Article

Abstract: An estimated 92% of the world’s population live in regions where people are regularly exposed to high levels of anthropogenic air pollution. Historically, research on the effects of air pollution have focused extensively on cardiovascular and pulmonary health. However, emerging evidence from animal and human studies has suggested that chronic exposures to air pollution detrimentally change the functioning of the central nervous system with the result being proteinopathy, neurocognitive impairment, and neurodegenerative disease. Case analyses of aging World Trade Center responders suggests that a single severe exposure may also induce a neuropathologic response. The goal of this report was to …explore the neuroscientific support for the hypothesis that inhaled particulate matter might cause an Alzheimer’s-like neurodegenerative disease, in order to consider proposed mechanisms and latency periods linking inhaled particulate matter and neurodegeneration, and to propose new directions in this line of research. Show more

Keywords: Cognitive impairment, dementia, exposures, inhalations, neurodegeneration, neuroinflammation, particulate matter, pathways, World Trade Center

DOI: 10.3233/JAD-200679

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 871-886, 2020

Authors: Zhang, Tianying | Han, Xiaojuan | Zhang, Xiaohua | Chen, Zhi | Mi, Yajing | Gou, Xingchun

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by brain function disorder and chronic cognitive function impairment. The onset of AD is complex and is mostly attributed to interactions between genetic factors and environmental factors. Lifestyle, dietary habits, and food consumption are likely to play indispensable functions in aged-related neurodegenerative diseases in elderly people. An increasing number of epidemiological studies have linked dietary fatty acid factors to AD, raising the point of view that fatty acid metabolism plays an important role in AD initiation and progression as well as in other central nervous system disorders. In this paper, we …review the effects of the consumption of various dietary fatty acids on AD onset and progression and discuss the detrimental and beneficial effects of some typical fatty acids derived from dietary patterns on the pathology of AD. We outline these recent advances, and we recommend that healthy dietary lifestyles may contribute to preventing the occurrence and decreasing the pathology of AD. Show more

Keywords: Alzheimer’s disease, fatty acid, ketone body, MUFA, PUFA

DOI: 10.3233/JAD-200558

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 887-904, 2020

Authors: Itzhaki, Ruth F.

Article Type: Article Commentary

Abstract: A recent study in vitro has shown that a sulphated polysaccharide, a type of fucoidan, has potent antiviral activity against SARS-Cov2. If the antiviral action were successful also for COVID-19 patients, it would be enormously valuable against not only acute disease but also long-term mental effects, which might include Alzheimer’s disease (AD). In a trial of AD patients, the apparent success of treatment with a polysaccharide, GV971, was suggested to result from antiviral action against herpes simplex virus type 1 (HSV1) in brain, a pathogen strongly implicated in AD, and that sulphation of GV971, making it fucoidan-like, might increase …its putative antiviral action. These data indicate that treatment of AD patients might be very effective using valacyclovir, a conventional antiviral, which inhibits viral replication, together with a fucoidan, which blocks virus entry into cells. Show more

Keywords: Alzheimer’s disease, antiviral, COVID-19, fucoidans, Herpes simplex virus type 1, SARS-Cov2

DOI: 10.3233/JAD-200986

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 905-906, 2020

Authors: Jouvent, Eric | Alili, Nassira | Hervé, Dominique | Chabriat, Hugues

Article Type: Short Communication

Abstract: In a woman with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) followed for 15 years, we observed magnetic resonance imaging white matter hyperintensities that vanished in the anterior temporal poles while the brain volume decreased unexpectedly. These imaging changes were transient and detected when the patient was being treated by valproic acid for stabilizing mood disturbances. This intriguing case supports that mechanisms underlying white matter hyperintensities can vary from one brain area to another and that important modifications of water influx into the brain tissue might be involved in some imaging features of CADASIL.

Keywords: Brain volume, CADASIL, valpromide, white matter hyperintensities

DOI: 10.3233/JAD-201086

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 907-910, 2020

Authors: Krell-Roesch, Janina | Syrjanen, Jeremy A. | Mielke, Michelle M. | Christianson, Teresa J. | Kremers, Walter K. | Machulda, Mary M. | Knopman, David S. | Petersen, Ronald C. | Vassilaki, Maria | Geda, Yonas E.

Article Type: Short Communication

Abstract: We examined the associations between baseline neuropsychiatric symptoms (NPS) and longitudinal changes in functional performance among 5,394 non-demented individuals aged ≥50 years (2,729 males; median age 74.2 years; 4,716 cognitively unimpaired, 678 mild cognitive impairment). After adjusting for age, sex, education, and medical comorbidities, NPS assessed by the Neuropsychiatric Inventory Questionnaire, clinical depression (Beck Depression Inventory score ≥13) and anxiety (Beck Anxiety Inventory score ≥10) were significantly associated with an increase in the Functional Activities Questionnaire score, indicating functional decline over time. This association may vary depending on the degree of cognitive impairment at baseline.

Keywords: Anxiety, depression, functional performance

DOI: 10.3233/JAD-200764

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 911-917, 2020

Authors: Haapanen, Marjut | Katisko, Kasper | Hänninen, Tuomo | Krüger, Johanna | Hartikainen, Päivi | Haapasalo, Annakaisa | Remes, Anne M. | Solje, Eino

Article Type: Short Communication

Abstract: Primary progressive aphasia (PPA) forms the spectrum of language variants of frontotemporal lobar degeneration (FTLD), including three subtypes each consisting of distinctive speech and language features. Repeat expansion in C9orf72 gene is the most common genetic cause of FTLD. However, thus far only little is known about the effects of the C9orf72 repeat expansion on the phenotype of PPA. This retrospective study aimed at determining the differences between the PPA phenotypes of the C9orf72 expansion carriers and non-carriers. Our results demonstrated no significant differences between these groups, indicating that the C9orf72 repeat expansion does not substantially …affect the phenotype of PPA. Show more

Keywords: C9orf72, frontotemporal dementia, frontotemporal lobar degeneration, primary progressive aphasia

DOI: 10.3233/JAD-200795

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 919-925, 2020

Authors: Gabere, Musa | Thu Pham, Nha Trang | Graff-Radford, Jonathan | Machulda, Mary M. | Duffy, Joseph R. | Josephs, Keith A. | Whitwell, Jennifer L. | for Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are two of the most common variants of atypical Alzheimer’s disease (AD). Both PCA and LPA are associated with relative sparing of hippocampus compared to neocortex, although hippocampal atrophy is observed. It is unclear whether regional patterns of hippocampal subfield involvement differ between PCA and LPA, and whether they differ from typical AD. Objective: To assess volume of specific subfields of the hippocampus in PCA, LPA, and typical AD. Methods: Fifty-nine patients with PCA and 77 patients with LPA were recruited and underwent T1-weighted MRI and …Pittsburgh Compound B (PiB) PET at Mayo Clinic. Thirty-six probable AD patients and 100 controls were identified from the Alzheimer’s Disease Neuroimaging Initiative. Hippocampal subfield volumes were calculated using Freesurfer, and volumes were compared between PCA, LPA, AD, and controls using Kruskal-Wallis and Dunn tests. Results: The LPA and PCA groups both showed the most striking abnormalities in CA4, presubiculum, molecular layer of the hippocampus, molecular and granule cell layers of the dentate gyrus, and the hippocampal-amygdala transition area, although atrophy was left-sided in LPA. PCA showed smaller volume of right presubiculum compared to LPA, with trends for smaller volumes of right parasubiculum and fimbria. LPA showed a trend for smaller volumes of left CA1 compared to PCA. The AD group showed smaller volumes of the right subiculum, CA1, and presubiculum compared to LPA. Conclusion: Patterns of hippocampal subfield atrophy differ across the different syndromic variants of AD. Show more

Keywords: Alzheimer’s disease, hippocampal subfields, hippocampus, logopenic progressive aphasia, magnetic resonance imaging, posterior cortical atrophy

DOI: 10.3233/JAD-200625

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 927-937, 2020

Authors: Ghilain, Matthieu | Hobeika, Lise | Lesaffre, Micheline | Schiaratura, Loris | Singh, Ashmita | Six, Joren | Huvent-Grelle, Dominique | Puisieux, François | Samson, Séverine

Article Type: Research Article

Abstract: Background: Music-based interventions appear to be efficient approaches to improve emotional, social, and cognitive functioning of patients with neurodegenerative diseases. Objective: Because benefits seem to increase with patient’s motor involvement, we studied sensorimotor synchronization (SMS) abilities of patients with cognitive impairments (Alzheimer’s disease, vascular and mixed dementia) and of patients with no evidence of cognitive impairments. More specifically, we compared the impact of a live performance by a musician to a video recording on SMS. Methods: SMS to a metronomic or a musical stimulus was assessed while patients watched a live musician or his pre-recorded video. …Results: SMS to a metronome was better than to music but this effect was modulated by the social context. While SMS to a metronome was better when facing a video than a live performance, there was no impact of social context on SMS to music. No group differences of SMS were found. Conclusion: The decrease in SMS to a metronome in a live performance may be due to social pressure. Such a pressure might be removed in pleasant social activities, like moving with music in a group, explaining the lack of effect on SMS to music. We found no performance differences in groups, suggesting relatively spared SMS in cognitively impaired patients. By showing that it is possible to encourage patients to synchronize with others, even when facing a video, our results indicate that SMS can be used as a relevant predictor in clinical trials and open up promising therapeutic options for isolated patients. Show more

Keywords: Aging, Alzheimer’s disease, cognitive impairment, dementia, motor activity, music therapy, social interaction

DOI: 10.3233/JAD-200521

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 939-949, 2020

Authors: Ruiter, Marvin | Herstel, Lotte J. | Wierenga, Corette J.

Article Type: Research Article

Abstract: Background: In an early stage of Alzheimer’s disease (AD), before the formation of amyloid plaques, neuronal network hyperactivity has been reported in both patients and animal models. This suggests an underlying disturbance of the balance between excitation and inhibition. Several studies have highlighted the role of somatic inhibition in early AD, while less is known about dendritic inhibition. Objective: In this study we investigated how inhibitory synaptic currents are affected by elevated Aβ levels. Methods: We performed whole-cell patch clamp recordings of CA1 pyramidal neurons in organotypic hippocampal slice cultures after treatment with Aβ-oligomers and in …hippocampal brain slices from AppNL-F-G mice (APP-KI). Results: We found a reduction of spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons in organotypic slices after 24 h Aβ treatment. sIPSCs with slow rise times were reduced, suggesting a specific loss of dendritic inhibitory inputs. As miniature IPSCs and synaptic density were unaffected, these results suggest a decrease in activity-dependent transmission after Aβ treatment. We observed a similar, although weaker, reduction in sIPSCs in CA1 pyramidal neurons from APP-KI mice compared to control. When separated by sex, the strongest reduction in sIPSC frequency was found in slices from male APP-KI mice. Consistent with hyperexcitability in pyramidal cells, dendritically targeting interneurons received slightly more excitatory input. GABAergic action potentials had faster kinetics in APP-KI slices. Conclusion: Our results show that Aβ affects dendritic inhibition via impaired action potential driven release, possibly due to altered kinetics of GABAergic action potentials. Reduced dendritic inhibition may contribute to neuronal hyperactivity in early AD. Show more

Keywords: Alzheimer’s disease, amyloid-β peptides, neural inhibition, synaptic transmission

DOI: 10.3233/JAD-200527

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 951-964, 2020