Current Alzheimer Research - Volume 20, Issue 4, 2023

Although microbiology and neurology are separate disciplines, they are linked to some infectious and neurological diseases. Today, microbiome is considered as one of the biomarkers of health by many researchers. This has led to the association of microbiome changes with many neurological diseases. The natural microbiota has many beneficial properties. If disrupted and altered, it can lead to irreversible complications and many neurological diseases. Therefore, according to previous studies, some preventive and therapeutic complementary therapies can prevent or restore microbiome dysbiosis and inflammation in the nervous system. With our current perception of the microbiological basis for different neurological disorders, both aspects of drug treatment and control of perturbations of the microbiome should be considered, and targeting them simultaneously will likely help to attain favorable results.

Background: For decades, evidence from observational studies and randomized controlled trials has converged to suggest associations of dietary components, foods, and dietary patterns with dementia. With population aging and a projected exponential expansion of people living with dementia, formulating nutritional strategies for dementia prevention has become a research hotspot. Objective: This review aimed to summarize available data on the roles of specific dietary components, food groups, and dietary patterns in dementia prevention among the elderly. Methods: Database search was carried out using PubMed, the Cochrane Library, EMBASE, and Medline. Results: Polyphenols, folate, vitamin D, omega-3 fatty acids, and β-carotene might decrease the risk of dementia. Consumption of green leafy vegetables, green tea, fish, and fruits is recommended. However, saturated fat, a diet rich in both dietary copper and saturated fat, aluminum from drinking water, and heavy drinking might increase dementia risk. Healthy dietary patterns, especially the Mediterranean diet, were proven to bring more cognitive benefits than single dietary components. Conclusion: We discussed and summarized the evidence on the roles of dietary components and patterns in dementia prevention among the elderly and found that some factors were closely associated with dementia risk in elderly. This may pave the way for the identification of dietary components and patterns as new therapeutic targets for dementia prevention in the elderly population.

Alzheimer's disease (AD) is the most common cause of neurodegenerative cognitive impairment. Brain stimulation techniques based on the delivery of transcranial shockwaves are currently being studied for their increasing popularity as an approach to modulate the human brain in a focal and targeted manner making this therapy a promising line of action against AD. In the present manuscript, we review for further understanding whether transcranial pulse stimulation (TPS) is a beneficial treatment for AD patients. PubMed, Google Scholar, and Cochrane databases were accessed with the search criteria set from year 2001 to 2022 and the following keywords were used: “transcranial pulse stimulation”, “focused ultrasound”, “noninvasive treatment and Alzheimer” and “TPS”. The search was focused on papers that provide evidence on the biological bases of the method, as well as its safety and tolerability. Even though more studies are needed with greater scientific rigor, such as a doubleblind and randomized study versus a placebo, TPS is an excellent and safe therapeutic option for AD. This novel approach accompanies currently available treatments and complements them, helping to maintain greater stability of the disease and slowing its progression. The biological effects and potential mechanisms of action of TPS for the improvement of cognitive function are further discussed.

Introduction: Alzheimer's disease (AD) is the most common form of dementia. There have been various proposed pharmacologic and non-pharmacologic treatments proposed for preventing cognitive decline in AD patients. Transcranial Direct Current Stimulation (tDCS) is a neuromodulation technique used to enhance cognitive functions and motor skills of the brain. Our study aimed to assess the effects of tDCS in AD patients, including effects on general cognitive status, memory, attention, executive functions, language, IQ, and neuropsychological effects, along with the factors influencing the outcomes. Methods: Systematic searches were conducted for relevant evidence using PubMed, ScienceDirect, and Cochrane Library databases for (Transcranial Direct Current Stimulation) and (Alzheimer’s). Duplicates were removed, and the remaining articles were screened for double-blind, placebo-controlled, randomized clinical trials (Phase III), case studies, and case series on patients diagnosed with AD using tDCS. The articles were assessed for full text, and studies were selected and analyzed to include in the review. Results: Overall, 20 studies were reviewed. Cognitive status, executive function and working memory, recognition memory, and language function may improve following AtDCS depending on the stimulation polarity and area stimulated. No significant effects of tDCS were seen on attention, associative memory, recall memory, visuospatial ability, and neuropsychiatric symptoms. Discussion: Therapy outcomes and the factors that could affect them were analyzed, which included the number of sessions taken, current density, stimulation polarity (cathodal/anodal/dual), area stimulated, training(s) given, and study timeline. Conclusion: tDCS is a well-tolerated therapy that can be used for improving several cognitive domains in patients having Alzheimer’s disease. Its treatment outcomes are affected by polarity (cathodal/ anodal), site of stimulation, number of sessions taken, and any training(s) given during the study.

Background: Intracerebral hemorrhage and cognitive decline are typical clinical presentations of cerebral amyloid angiopathy (CAA). Objective: To determine whether magnetic resonance imaging (MRI) features differ between CAA with hemorrhagic versus cognitive onset. Methods: In this retrospective study, sixty-one patients with CAA were classified by onset presentation of the disease: hemorrhage (n = 31) or cognitive decline (n = 30). The two groups were compared for MRI markers of small vessel disease, namely cerebral microbleeds (CMBs), cortical superficial siderosis, white matter hyperintensities (WMHs), enlarged perivascular spaces, cortical microinfarcts, and visual rating scales for cortical atrophy. In the patients with cognitive onset, further exploratory analyses investigated MRI markers according to cerebrospinal fluid (CSF) and neuropsychological profiles. Results: Patients with cognitive onset showed a higher prevalence of CMBs (p < 0.001), particularly in temporal (p = 0.015) and insular (p = 0.002) lobes, and a higher prevalence of WMHs (p = 0.012). Within the cognitive onset group, 12 out of 16 (75%) patients had an Alzheimer’s disease (AD) CSF profile but did not differ in MRI markers from those without AD pathology. Patients with cognitive onset displayed a multidomain profile in 16 out of 23 (70%) cases; patients with this profile showed increased WMHs and CMBs in parietal lobes compared with the amnestic group (p = 0.002) and dysexecutive group (p = 0.032), respectively. Conclusion: Higher burdens of WMHs and CMBs, especially in temporal and insular lobes, are associated with the cognitive onset of CAA. MRI markers could help to shed light on the clinical heterogeneity of the CAA spectrum and its underlying mechanisms.

Background: The integrity of Locus Coeruleus can be evaluated in vivo using specific Magnetic Resonance Imaging sequences. While this nucleus has been shown to be degenerated both in post-mortem and in vivo studies in Alzheimer’s Disease, for other neurodegenerative dementias such as Dementia with Lewy Bodies this has only been shown ex-vivo. Objective: To evaluate the integrity of the Locus Coeruleus through Magnetic Resonance Imaging in patients suffering from Dementia with Lewy Bodies and explore the possible differences with the Locus Coeruleus alterations occurring in Alzheimer’s Dementia. Methods: Eleven patients with Dementia with Lewy Bodies and 35 with Alzheimer’s Dementia were recruited and underwent Locus Coeruleus Magnetic Resonance Imaging, along with 52 cognitively intact, age-matched controls. Images were analyzed applying an already developed template-based approach; Locus Coeruleus signal was expressed through the Locus Coeruleus Contrast Ratio parameter, and a locoregional analysis was performed. Results: Both groups of patients showed significantly lower values of Locus Coeruleus Contrast Ratio when compared to controls. A different pattern of spatial involvement was found; patients affected by Dementia with Lewy bodies showed global and bilateral involvement of the Locus Coeruleus, whereas the alterations in Alzheimer’s Dementia patients were more likely to be localized in the rostral part of the left nucleus. Conclusions: Magnetic Resonance Imaging successfully detects widespread Locus Coeruleus degeneration in patients suffering from Dementia with Lewy Bodies. Further studies, in larger cohorts and in earlier stages of the disease, are needed to better disclose the potential diagnostic and prognostic role of this neuroradiological tool.

Background: Transglutaminase 2 is an ubiquitously multifunctional enzyme and the most widely studied of the transglutaminase family. Consistent with its role in promoting post-translational modifications of proteins, Transglutaminase 2 is involved in many physiological processes such as apoptosis, signal transduction, and cellular adhesion. Several findings indicate that Transglutaminase 2 plays a role in the pathological processes of various inflammation-related diseases, including neurodegenerative diseases. Objective: We tested the potential modulatory effects on amyloid-β-induced Transglutaminase 2 expression and activities of 2-pentadecyl-2-oxazoline, a plant-derived agent, which has shown effectiveness against chronic pain and associated neuropsychiatric disorders, both in mouse and human microglial cell lines. Methods: We used biochemistry, molecular and cell biology techniques to evaluate the potential modulatory effects on amyloid-β-induced Transglutaminase 2 expression and activities of 2- pentadecyl-2-oxazoline in mouse and human microglial cell lines. Results: 2-pentadecyl-2-oxazoline was able to modulate amyloid-β-induced Transglutaminase 2 expression and activities in mouse and human microglial cell lines. Conclusion: Transglutaminase 2 confirms its role as a neuroinflammation marker, the inhibition of which could be a potential preventive and therapeutic approach, while 2-pentadecyl-2-oxazoline is a potent modulator of the amyloid-β-induced Transglutaminase 2 expression and activities in mouse and human microglial cell lines.