Anne Koivisto

BACKGROUND: Alzheimer disease (AD) and idiopathic normal pressure hydrocephalus (iNPH) are neurodegenerative diseases causing memory decline. Previous studies have demonstrated an altered gut microbiome (GM) in both conditions. In this study, we compared the GM composition between the groups to find out how if the GM composition differed between the cognitively healthy individuals (CO) and AD groups, as well as between the AD and iNPH groups. METHODS: Thirty-seven CO participants, 21 mild AD patients and 10 participants with shunted iNPH gave fecal samples, which were subjected to 16S amplicon sequencing. Then, genus-level differences were analyzed. Information about comorbidities and diet was collected, and cognitive function was evaluated. RESULTS: Compared with the CO group, Anaerovorax and an unknown genus of the Comamonadaceae family increased, whereas Enterobacter, Absicoccus, Buttiauxella, Raoultella, and Lacticaseibacillus decreased in the AD group. Compared with the iNPH group, Paramuribaculum, an unknown genus of the Desulfovibrionaceae family, Ruficoccus and Mitsuokella increased, whereas Anaeromassilibacillus and Desulfovibrio decreased in the AD group. CONCLUSIONS: We demonstrated differences in the GM composition between the AD and CO groups, as well as between the AD and iNPH groups. To our knowledge, this is the first report to compare the 2 neurodegenerative diseases and demonstrate GM differences.

Ambient air pollution is a global problem contributing to the development of numerous diseases, including neurodegenerative disorders. Using a mobile exposure system, we investigated the molecular changes in human olfactory cleft mucosal (hOM) cells, a proxy to brain effects, from healthy and Alzheimer's disease (AD) patients modulated by exposure to real-world ambient air. In the samples, exposed at the air-liquid interface (ALI) in a clean, Background locality (very low levels of pollutants) and an Industrial site (air pollution within recommended limits), the production of immune response-related molecules, lipid peroxidation and global RNA expression changes were assessed. The production of leukemia-inhibitory factor (LIF) was increased in the samples from healthy, but not AD individuals in the Industrial locality. No changes in the levels of 15-F2t- isoprostane, a parameter of lipid peroxidation, were detected. When compared with the synthetic air (a blank control) numerous biological processes and KEGG pathways were enriched in the samples exposed in the Industrial, but not the Background locality. In the samples from the healthy subjects, the neurodegenerative disorder-related pathways were significantly affected, indicating the potential of the ambient air to contribute to these diseases. In the AD samples exposed in the Industrial locality, when compared with the Background site, an inflammation-related response was detected, suggesting the potential to exacerbate immune response reactions as a result of ambient air pollution. In summary, our data indicate that exposure to air pollutants, without exceeding the recommended limits, might have significant molecular consequences, potentially contributing to the development of neurodegenerative disorders.

Ambient air pollution is a global problem contributing to the development of numerous diseases, including neurodegenerative disorders. Using a mobile exposure system, we investigated the molecular changes in human olfactory cleft mucosal (hOM) cells, a proxy to brain effects, from healthy and Alzheimer's disease (AD) patients modulated by exposure to real-world ambient air. In the samples, exposed at the air-liquid interface (ALI) in a clean, Background locality (very low levels of pollutants) and an Industrial site (air pollution within recommended limits), the production of immune response-related molecules, lipid peroxidation and global RNA expression changes were assessed. The production of leukemia-inhibitory factor (LIF) was increased in the samples from healthy, but not AD individuals in the Industrial locality. No changes in the levels of 15-F2t- isoprostane, a parameter of lipid peroxidation, were detected. When compared with the synthetic air (a blank control) numerous biological processes and KEGG pathways were enriched in the samples exposed in the Industrial, but not the Background locality. In the samples from the healthy subjects, the neurodegenerative disorder-related pathways were significantly affected, indicating the potential of the ambient air to contribute to these diseases. In the AD samples exposed in the Industrial locality, when compared with the Background site, an inflammation-related response was detected, suggesting the potential to exacerbate immune response reactions as a result of ambient air pollution. In summary, our data indicate that exposure to air pollutants, without exceeding the recommended limits, might have significant molecular consequences, potentially contributing to the development of neurodegenerative disorders.

BACKGROUND: During the Covid19 pandemic restrictions, overall traffic volume decreased in Finland. Fatigue and sleepiness while driving are common risks factors for fatal motor vehicle accidents. OBJECTIVE: We analyzed the effects of Covid19 pandemic restrictions on the number of Fatal sleepiness-related motor vehicle accidents (FSMVA) during and before the pandemic. METHODS: All fatal motor vehicle accidents during the years 2016-2022 were studied using Finnish Road Accidents data. Of the 1226 accidents, 235 formed FSMVA group and the others the control group. FSMVA values before the pandemic restrictions were compared with the values during the pandemic period. Statistical analysis was performed with Stata 18.5. RESULTS: The FSMVA proportion of fatal crashes before the pandemic period was 22.7%, and during the pandemic 13.4%(p < 0.001). The COVID years were significantly associated with a lower mortality rate (fatal accidents per million vehicle-kilometers) from FSMVA(p = 0.012). According to logistic regression, the probability of FSMVA was lower in the youngest age group (OR 0.6) and higher in the early morning (OR 2.0) and mid-morning (OR 1.7). Furthermore, the incidence of FSMVA increased when the blood alcohol concentration (BAC) was ≥0.5‰ (OR 2.2). During the pandemic, predictions of FSMVA decreased in the summer months (from 27% to 13%), in the early morning (from 38% to 16%) and in the afternoon (from 21% to 9%) compared to the pre-pandemic era. Furthermore, the FSMVA was observed to be less prevalent during the pandemic, particularly among individuals under the age of 25 (8% versus 21%). CONCLUSION: Proportion of fatal crashes and mortality rate of FSMVA decreased during the pandemic period compared to the pre-pandemic era. A possible explanation for the results may be the increase in remote work, which effectively reduced drowsy driving during pandemic era.