Journal of Alzheimer's Disease Reports - Volume 8, issue 1

Authors: O’Caoimh, Rónán | Foley, Mary J. | Timmons, Suzanne | Molloy, D. William

Article Type: Research Article

Abstract: Background: The Montreal Cognitive Assessment (MoCA) is recommended by the Movement Disorder Society for cognitive testing in movement disorders including Parkinson’s disease (PD) and lewy body dementia. Few studies have compared cognitive screening instruments in these diseases, which overlap clinically. Objective: To compare the MoCA and Quick Mild Cognitive Impairment (Qmci) screen in this population. Methods: Patients attending memory and movement disorder clinics associated with a university hospital had the MoCA and Qmci screen performed and diagnostic accuracy compared with the area under the receiver operating characteristic curve (AUC). Duration and severity of movement …disorders was assessed using the Unified PD Rating Scale (UPDRS). Results: In total, 133 assessments were available, median age 74±5. Median education was 11±4 years and 65% were male. Median total UPDRS score was 37±26. Median Qmci screen was 51±27, median MoCA was 19±10. There were statistically significant differences in test scores between those with subjective symptoms but normal cognition, mild cognitive impairment (MCI) and dementia (p  < 0.001). The Qmci screen had significantly greater accuracy differentiating normal cognition from MCI versus the MoCA (AUC 0.90 versus 0.72, p  = 0.01). Both instruments had similar accuracy in identifying cognitive impairment and separating MCI from dementia. The median administration time for the Qmci screen and MoCA were 5.19 and 9.24 minutes (p  < 0.001), respectively. Conclusions: Both the MoCA and Qmci screen have good to excellent accuracy in a population with movement disorders experiencing cognitive symptoms. The Qmci screen was significantly more accurate for those with early symptoms and had a shorter administration time. Show more

Keywords: Alzheimer’s disease, cognitive assessment screening instrument, lewy body disease, Montreal Cognitive Assessment, movement disorders, Parkinson’s disease

DOI: 10.3233/ADR-230207

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 971-980, 2024

Authors: Chittimalli, Kishore | Adkins, Stephen | Arora, Sanjay | Singh, Jagdish | Jarajapu, Yagna P.R.

Article Type: Research Article

Abstract: Background: The APP/PS1 mouse model recapitulates pathology of human Alzheimer’s disease (AD). While amyloid-β peptide deposition and neurodegeneration are features of AD, the pathology may involve inflammation and impaired vascular regeneration. Objective: This study evaluated inflammatory environments in the brain and bone marrow (BM), and the impact on brain microvascular density. Methods: BM and frontal cortex from male nine-month-old APP/PS1 or the control C57Bl6/j mice were studied. Vascular density and inflammatory cells were evaluated in the sections of frontal cortex by immunohistochemistry. Different subsets of hematopoietic stem/progenitor cells (BM) and monocyte-macrophages were characterized by flow cytometry …and by clonogenic assays. Myelopoietic or inflammatory factors were evaluated by real-time RT-PCR or by western blotting. Results: CD34+ or CD31+ vascular structures were lower (p  < 0.01, n  = 6) in the frontal cortex that was associated with decreased number of Lin− Sca-1+ cKit+ vasculogenic progenitor cells in the BM and circulation (p  < 0.02, n  = 6) compared to the control. Multipotent progenitor cells MPP4, common lymphoid, common myeloid and myeloid progenitor cells were higher in the APP/PS1-BM compared to the control, which agreed with increased numbers of monocytes and pro-inflammatory macrophages. The expression of pro-myelopoietic factors and alarmins was higher in the APP/PS1 BM-HSPCs or in the BM-supernatants compared to the control. Frontal cortices of APP/PS1 mice showed higher number of pro-inflammatory macrophages (CD11b+ F4/80+ or CD80+ ) and microglia (OX42+ Iba1+ ). Conclusions: These findings show that AD pathology in APP/PS1 mice is associated with upregulated myelopoiesis, which contributes to the brain inflammation and decreased vascularity. Show more

Keywords: Alarmins, Alzheimer’s disease, APP/PS1 mice, bone marrow, frontal cortex, inflammation, myelopoiesis

DOI: 10.3233/ADR-240024

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 981-998, 2024

Authors: Zhang, Weiyi | Fu, Weilun | Zhang, Yumei

Article Type: Research Article

Abstract: Background: Effect of stenosis of vertebrobasilar artery (VBA) on cognitive function is elusive. Objective: To investigate association of cerebral hypoperfusion and poor collaterals with vascular cognitive impairment (VCI) in severe VBA stenosis patients. Methods: We consecutively enrolled patients with severe VBA stenosis confirmed by digital subtraction angiography who underwent computed tomographic perfusion (CTP) and cognitive assessments. Patients were divided into poor or good collaterals groups according to the collateral circulation status, and were grouped into different perfusion groups according to CTP. Cognitive function was measured by Montreal Cognitive Assessment (MoCA), Clock Drawing Test, Stroop Color Word …Test, Trail Making Test, Digital Span Test, Auditory Verbal Learning Test, and Boston Naming Test scales. The association of cerebral perfusion and collaterals with VCI were explored. Results: Among 88 eligible patients, VCI occurred in 51 (57.9%) patients experienced. Poor collateral was present in 73 (83.0%) patients, and hypoperfusion in 64 (72.7%). Compared with normal perfusion patients, the odds ratio with 95% confidence interval for VCI was 12.5 (3.7–42.4) for overall hypoperfusion, 31.0 (7.1–135.5) for multiple site hypoperfusion, 3.3 (1.0–10.5) for poor collaterals, and 0.1 (0–0.6) for presence of posterior communicating artery (PcoA) compensated for posterior cerebral artery (PCA) and basilar artery (BA). Additionally, decreased scores of cognitive function tests occurred in patients with decompensated perfusion or poor collaterals. Conclusions: Hypoperfusion and poor collaterals were positively associated with cognitive impairment in patients with severe VBA. However, PcoA compensated for the PCA and BA had a protective role in cognitive impairment development. Show more

Keywords: Alzheimer’s disease, cerebral perfusion, collateral circulation, vascular cognitive impairment, vertebrobasilar artery stenosis

DOI: 10.3233/ADR-240007

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 999-1007, 2024

Authors: De Guia, Isaiah-Lorenzo | Eslick, Shaun | Naismith, Sharon L. | Kanduri, Swathi | Shah, Tejal M. | Martins, Ralph N.

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is the most common type of dementia, which is characterised by progressive memory loss and accumulation of hallmark markers amyloid-β (Aβ) and neurofibrillary tangles in the diseased brain. The current gold standard diagnostic methods have limitations of being invasive, costly, and not easily accessible. Thus, there is a need for new avenues, such as imaging the retina for early AD diagnosis. Sleep disruption is symptomatically frequent across preclinical and AD subjects. As circadian activity, such as the sleep-wake cycle, is linked to the retina, analysis of their association may be useful additions for achieving predictive AD diagnosis. …In this narrative review, we provide an overview of human retina studies concerning the deposition of Aβ, the role of the retina in sleep-wake cycle, the disruption of sleep in AD, and to gather evidence for the associations between Aβ, the retina, and sleep. Understanding the mechanisms behind the associations between Aβ, retina, and sleep could assist in the interpretation of retinal changes accurately in AD. Show more

Keywords: Alzheimer’s disease, amyloid, dementia, retina, sleep

DOI: 10.3233/ADR-230150

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 1009-1021, 2024

Authors: Caccamo, Martina | Urso, Daniele | Nanni, Alfredo Gabriele | Gnoni, Valentina | Giugno, Alessia | Vitulli, Alessandra | Vilella, Davide | Zecca, Chiara | Dell’Abate, Maria Teresa | Anastasia, Antonio | De Blasi, Roberto | Introna, Alessandro | Logroscino, Giancarlo

Article Type: Case Report

Abstract: The presence of parkinsonism features in primary progressive aphasia (PPA) is a subject of ongoing research. These features are usually more pronounced in the advanced stages of the disease, particularly in the non-fluent/agrammatic subtype, and are exceptionally rare in the logopenic variant (lvPPA). Here we report a case of a 63-year-old man presenting as language impairment, predominantly naming and word-finding difficulties, emerged alongside a left-sided internal tremor. Neurological examination revealed bilateral, left-side predominant rigidity, bradykinesia, and resting tremor. Notably, anosmia and constipation were present. Language assessments showed preserved single-word comprehension, object knowledge, and a minimal apraxia of speech, as well …as sentence repetition issues. Neuroimaging and biomarker analysis supported a diagnosis of primary progressive logopenic aphasia with amyloid pathology co-existing with prominent and early parkinsonism. This case underlines the intricate relationship between language disorders, parkinsonism, and amyloid pathology in lvPPA. Show more

Keywords: Alzheimer’s disease, amyloid, amyloid PET, logopenic variant, parkinsonism, primary progressive aphasia

DOI: 10.3233/ADR-230168

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 1023-1030, 2024

Authors: Chen, Anqi | Wang, Yuquan | Hu, Yue-Qing

Article Type: Research Article

Abstract: Background: Many observational studies have investigated the link between the gut microbiota and Alzheimer’s disease (AD), but the causality remains uncertain. Objective: This study aimed to evaluate the causal impact of gut microbiota on AD. Methods: A two-sample Mendelian randomization (MR) study was conducted employing summary data. Summary statistics for AD were from the latest genome-wide association study (cases and proxy cases: 85,934; controls: 401,577). Summary data for gut microbiota were acquired from MiBioGen consortium. Causal effect estimations primarily relied on the inverse variance weighting method along with the sensitivity analyses for testing for pleiotropy and …heterogeneity. Additionally, reverse MR analyses were performed to examine potential reverse causality. Results: Seven gut microbiota were identified as associated with AD risk. Order Selenomonadales (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.03–1.24, p  = 0.01), Family Pasteurellaceae (OR 1.07, 95% CI 1.01–1.13, p  = 0.01), and Genus Methanobrevibacter (OR 1.07, 95% CI 1.00–1.13, p  = 0.04) were correlated with an elevated likelihood of AD, while Class Mollicutes (OR 0.87, 95% CI 0.79–0.95, p  = 0.00), Genus Ruminiclostridium9 (OR 0.87, 95% CI 0.78–0.97, p  = 0.01), Genus Clostridiuminnocuumgroup (OR 0.94, 95% CI 0.89–0.99, p  = 0.03), and Genus Eggerthella (OR 0.94, 95% CI 0.89–1.00, p  = 0.04) exerted beneficial impact in mitigating AD. No statistically significant reverse causality was found between AD and each of these seven specific gut microbiota species. Conclusions: This study unveiled a causal link between certain gut microbiota and AD, offering new insights for advancing clinical treatments. Show more

Keywords: Aging, Alzheimer’s disease, gut microbiota, Mendelian randomization, neuropsychiatric disorder

DOI: 10.3233/ADR-240071

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 1031-1040, 2024

Authors: Sharif, Azaz Bin | Jahan, Ishrat | Hasan, A.B.M. Nahid

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a growing public health concern affecting millions of individuals worldwide. This disease burden is exacerbated in countries like Bangladesh, where public awareness and knowledge about the condition remains limited. Objective: This study aimed to assess the level of AD knowledge, awareness, and perceived threat among family caregivers of individuals with chronic physical conditions of Bangladesh. Methods: A descriptive cross-sectional study was conducted among the caregivers of patients selected via convenience sampling in six public hospitals between October 2022 and March 2023. The data was collected via face-to-face interviews employing a semi-structured …questionnaire that contained information about socio-demographic characteristics, personal experiences with AD, knowledge of AD, level of awareness regarding AD, and perceived threat toward AD. Results: The findings revealed a poor knowledge of AD among the study participants. Regarding AD awareness, 52.5% considered memory loss in older individuals abnormal, 26.2% attributed AD to causes like black magic, psychological distress, or bad eyes. Regarding perceived threat, 60.2% wanted to assess their AD risk, while 68.2% disagreed with the likelihood of developing the disease. Multiple linear regression analysis revealed that age, place of residence, education, and employment status significantly contribute to AD knowledge scores. Conclusions: This study highlights the urgent need for public education and awareness campaigns to address the knowledge gap and reduce stigmatization associated with AD in Bangladesh. Targeted efforts, particularly among older age groups and rural communities, can enhance understanding and improve the quality of care and support for AD patients and their caregivers. Show more

Keywords: Alzheimer’s disease, awareness, Bangladesh, knowledge, perceived threat

DOI: 10.3233/ADR-240055

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 1041-1054, 2024

Authors: Singhrao, Sim K. | Consoli, Claudia | Dennison, Sarah R. | Kanagasingam, Shalini | Welbury, Richard

Article Type: Research Article

Abstract: Background: Glycogen synthase-3 kinase (GSK3) is one of the major contributors of tau hyperphosphorylation linked to neurofibrillary tangles in Alzheimer’s disease (AD). Objective: To determine a mechanism of GSK-3β activation by two periodontal bacteria consistently confirmed in AD autopsied brains. Methods: Porphyromonas gingivalis FDC381 and Actinomyces naeslundii ATCC10301 conditioned media were collected. IMR-32 cells were challenged for 48 h with the conditioned media alongside P. gingivalis (ATCC33277) ultrapurified lipopolysaccharide (LPS) designated Pg.LPS under established cell culture conditions either alone or combined. Gene expression and protein analyses for GSK-3β were carried out. Results: …qPCR demonstrated that GSK-3β gene was overexpressed in IMR-32 cells treated with Pg.LPS with a 2.09-fold change (p  = 0.0005), while A. naeslundii treated cells demonstrated 1.41-fold change (p  = 0.004). Western blotting of the cells challenged with Pg.LPS (p  = 0.01) and A. naeslundii conditioned medium (p  = 0.001) demonstrated the 37 kDa band for each treatment with variable intensity across the medium control. Immunohistochemistry with the GSK-3β of the IMR-32 cells challenged with Pg.LPS and A. naeslundii alone demonstrated cytoplasmic and nuclear localization. Conclusions: Exposure to various bacterial factors upregulated the gene expression of GSK-3β. Western blotting for GSK-3β confirmed the presence of the cleaved fragment by Pg.LPS (37 kDa band p  = 0.01) and A. naeslundii conditioned medium (37 kDa band p  = 0.001). Immunostaining demonstrated both cytoplasmic and nuclear localization of GSK-3β. Therefore, Pg.LPS and an unknown factor from the A. naeslundii conditioned medium mediated GSK-3β activation via its transcriptionally active, cleaved, fragment. These virulence factors in the body appear to be detrimental to brain health. Show more

Keywords: Actinomyces naeslundii, Alzheimer’s disease, glycogen synthase-3 kinase, inflammation, LPS, Porphyromonas gingivalis

DOI: 10.3233/ADR-240066

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 1055-1067, 2024

Authors: Kunkler, Michelle Celine | Falkenreck, Julia Maria | Ophey, Anja | Dencker, Katharina | Friese, Andrea | Jahr, Petra | Kalbe, Elke | Nelles, Gereon | Polidori, M. Cristina

Article Type: Research Article

Abstract: Background: Age-related neuronal changes impact cognitive integrity, which is a major contributor to health and quality of life. The best strategy to prevent cognitive decline and Alzheimer’s disease is still debated. Objective: To investigate the long-term effects of the eight-week multicomponent training program BrainProtect® on cognitive abilities compared to general health counseling (GHC) in cognitively healthy adults in Germany. Methods: Healthy adults (age ≥50 years) previously randomized to either GHC (n  = 72) or BrainProtect (intervention group, IG, n  = 60) for eight-weeks (once weekly, 90 minutes, group-based) underwent a comprehensive neuropsychological test battery and health-related quality …of life (HRQoL) evaluation 3- and 12-months after intervention end. Results: Dropout rates were n  = 8 after 3 months and n  = 19 after 12 months. No significant long-term effect of BrainProtect was observed for the primary endpoint Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-Plus) total score. Logical reasoning was significantly improved (p  = 0.024) 12 months after completion of the training program in IG participants compared to the GHC group independent of sex, age, education, diet, and physical activity. In IG participants, thinking flexibility (p  = 0.019) and confrontational naming (p  = 0.010) were improved 3 months after completing the intervention compared to the GHC group, however, after conservative Bonferroni adjustment, significance was lost. Conclusions: BrainProtect® independently improved logical reasoning compared to GHC up to 12 months after cognitive training’s end in healthy adults. To uncover the long-term clinical significance of multicomponent cognitive training in healthy adults, studies with larger sample size and frequent follow up visits are necessary. Show more

Keywords: Alzheimer’s disease, cognitive integrity, cognitive training, dementia prevention, long-term effects

DOI: 10.3233/ADR-230199

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 1069-1087, 2024

Authors: Renard, Dimitri | Sangare, Birama | Youssouf, Ansma | Thouvenot, Eric

Article Type: Short Communication

Abstract:  Alzheimer’s disease and cerebral amyloid angiopathy (CAA) are often associated. Amyloid accumulation within leptomeningeal and small/median-sized cerebral blood vessels in CAA results in vessel fragility, leading to spontaneous leptomeningeal bleeding, lobar intracerebral hemorrhage (ICH) and cerebral microbleeds. CAA is also associated with non-traumatic subdural hematoma. The role of CAA-related vessel fragility in hemorrhagic complications after trauma, brain surgery, and intracranial drain insertion in CAA is unknown. We present two sporadic CAA patients with intracranial drain-related ICH, probably due to different underlying mechanisms, related to indirect and direct CAA-associated vessel fragility.

Keywords: Alzheimer’s disease, cerebral amyloid angiopathy, decompressive craniectomy, intracranial drain, intracerebral hemorrhage

DOI: 10.3233/ADR-240086

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 1089-1092, 2024