crucial in prevention eorts and for planning cost- eective interventions. More re­cently, infectious agents have gained the attention of the research community, and some have been implicated in the etiology of AD and related dementias (Honjo et al.,

mechanisms behind sex dierences, if any, in the association between Hp and de­mentia risk are lacking. In fact, the association among men between Hp infection and neurodegeneration based on brain magnetic resonance imaging data added support to previous ndings regarding Hp seropositivity’s association with inci­dent dementia among men only, using retrospective cohort data with NHANES III– Medicare data (Beydoun et al., 2018; Park et al., 2021).

Aer AD, PD is the second most common neurodegenerative disorder and is the most frequently diagnosed movement disorder with an estimated prevalence of 1– 2 percent in the United States’ older population (Bomasang- Layno et al., 2015; Dalle & Mabandla, 2018; Ossowska & Lorenc- Koci, 2013; Shamim et al., 2019; Beydoun, Chen et al., 2022; Beydoun, Saquib et al., 2022). Evidence suggests that genetic mu­tations and environmental toxins interact, contributing to PD’s etiology (Dalle & Mabandla, 2018; Dick et al., 2007; Beydoun, Chen et al., 2022; Beydoun, Saquib et al., 2022). PD results from the progressive degeneration of dopaminergic neurons in the nigrostriatal pathway, triggering dopamine deciency within the substantia nigra pars compacta (Dalle & Mabandla, 2018; Dick et al., 2007; Beydoun, Chen et al., 2022; Beydoun, Saquib et al., 2022). PD has established motor symptoms, including resting tremor, rigidity, postural instability, akinesia, hyperkinesia, and bradykinesia (Dalle & Mabandla, 2018; Diederich & McIntyre, 2012; Frandsen et al., 2014; Ossowska & Lorenc- Koci, 2013; Beydoun, Chen et al., 2022; Beydoun, Saquib et al., 2022). PD also has recently been shown to exhibit non- motor symptoms (NMS) or comorbid conditions, oen preceding or co- occurring with motor symptoms (Bomasang­Layno et al., 2015; Dalle & Mabandla, 2018; Dissanayaka et al., 2019; Haasum et al., 2016; Martinez- Ramirez et al., 2016; Shamim et al., 2019; Beydoun, Chen et al., 2022; Beydoun, Saquib et al., 2022). NMS, which include several neuropsychiatric and au­tonomic dysfunctions, such as fatigue, anxiety, leg pain, insomnia, urinary urgency and nocturia, excessive salivation, diculty maintaining concentration, and depres­sion, are highly prevalent (approximately 62 percent) but oen unrecognized and undertreated, leading to signicant decrement in PD patients’ quality of life and in their caregivers (Costa et al., 2012; Dalle & Mabandla, 2018; Beydoun, Chen et al., 2022; Beydoun, Saquib et al., 2022). On average, PD patients have 7.8 NMS, with the psychiatry eld being the most impacted (Costa et al., 2012). Late- onset PD patients (over the age of 60 years) tend to have more severe motor symptoms and more fre­quent NMS, coupled with a faster course and shorter survival than early- onset PD patients (Virameteekul et al., 2021; Yuan et al., 2021; Beydoun, Chen et al., 2022; Beydoun, Saquib et al., 2022).

Hp infection has been hypothesized to be involved in the pathogenesis of PD, and its eradication can possibly alleviate symptoms and improve PD treatment ef­fectiveness. One hypothesis is that Hp may increase neurotoxic production of

2022). e resulting lesions produce a wide variety of neurological symptoms in­cluding vision impairment, numbness and tingling, focal weakness, and bladder and bowel incontinence, as well as cognitive dysfunction, rendering it one of the dementing illnesses (Tai et al., 2022). Acute relapses oen occur during young adulthood followed by a gradual progressive stage that causes permanent disability

worldwide (WHO, 2022). Lifetime prevalence of MDD in the United States is esti­mated to be higher among women compared to men, namely 20% vs. 12%, respec­tively (Kessler et al., 1994; Beydoun et. al, 2015). More recent estimates indicate an overall lifetime prevalence of 18.6% (Kessler et al., 2005), and global range of 2% to 21% (Gutiérrez-Rojas, 2020).. is sex dierential has been ascribed to hormonal factors, and among women to the high- risk postpartum period (Brummelte & Galea, 2010). Approximately 20 million people in the United States suer a depres­sive illness every year. Common risk factors for MDD include stressful life events, social isolation, substance abuse, chronic physical illness, a family history of MDD, or a history of sexual or other physical abuse (Peek- Asa et al., 2005). Depression is oen accompanied by a proinammatory process, which can increase morbidity risk from cardiovascular disease (Ariyo et al., 2000, Panagiotakos et al., 2004). Psychoneuroimmunological dysfunctional processes have been proposed in order to elucidate depression’s origins (Zunszain et al., 2013). In fact, depressed adults tend to have activated peripheral immune systems and exaggerated proinammatory cytokine production, coupled with abnormalities in neuroendocrine functions, neurotransmitter metabolism, and regional brain activity, leading to an increased number of depressive symptoms (Zunszain et al., 2013). When cytokines are acutely administered to humans and animals, the result is a sickness behavior that is compa­rable to depression (Zunszain et al., 2013). Moreover, when adults are under chronic stress, a proinammatory phenotype ensues and leads to recurrent depressive epi­sodes (Zunszain et al., 2013).

Given the salient proinammatory state coupled with folate deciency triggered by Hp infection, as discussed earlier, it is expected that Hp infection would also as­sociate with elevated depressive symptoms and be more prevalent among MDD patients as opposed to healthy controls. In a cross- sectional study of 975 Japanese in­dividuals (503 females; mean age, 44 ± 8 years) who underwent a health checkup, Hp seropositive individuals were at signicantly greater risk for psychological distress and depression compared to their seronegative counterparts, particularly among younger women less than 50 years of age who also had atrophic gastritis versus those who did not have either of the two conditions (OR: 16.4, 95 percent CI: 3.45– 94.9 for psychological distress and OR: 2.86, 95 percent CI: 1.31– 6.05 for depression) (Takeoka et al., 2017). In another cross- sectional study of 5558 inhabitants of Tianjin, China, Hp infection was diagnosed using carbon- 13 breath test methodology, while depressive symptoms were assessed with the 20- item Self- rating Depression Scale (SDS) in its Chinese validated version with three cutos (45, 48, and 50) to reect elevated depressive symptoms (Gu et al., 2019). In multivariable logistic regression models, ORs and 95 percent CIs of elevated depressive symptoms versus Hp infec­tion were 1.25 (1.01– 1.56), 1.46 (1.11– 1.91), and 1.46 (1.05– 2.06) across the three cutos in women, a result not replicated among men (Gu et al., 2019). Another lon­gitudinal study, however, found that only seropositivity in cytomegalovirus may be associated with incidence of depression over a 10- year follow- up period, but no re­lationship was detected for Hp seropositivity (Simanek et al., 2019). Nevertheless,

there is a paucity of studies, particularly longitudinal ones examining similar re­search questions. New evidence in fact points to the contrary, whereby eradication of Hp may trigger short- term depressive disorder (Tsai et al., 2021). However, a more recent Mendelian randomization study implicated both depression and Hp infection in the etiology of peptic ulcer disease (Wu et al., 2021), and a recent systematic re­view of observational studies and randomized controlled trials found that patients who showed no improvement in functional dyspepsia aer Hp eradication were seen to improve on antidepressant therapy, suggesting benecial eects of including antidepressants in standard Hp regimens (Al Quraan et al., 2019).