Emotional and Psychological Distress of Persons Involved in the Care of Patients with Alzheimer Disease Predicts Falls and Fractures in Their Care Recipients

Maggio, Dario; Ercolani, Sara; Andreani, Sonia; Ruggiero, Carmelinda; Mariani, Elisabetta; Mangialasche, Francesca; Palmari, Nicola; Mecocci, Patrizia

doi:10.1159/000288774

Cited by 18 publications

(23 citation statements)

References 36 publications

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“…3 In our study, the favorable rs8099917 TT genotype was found in 100% of the rs12979860 CC patients compared to 31% of CT and 10% of TT patients only. Among the 42 rs12979860 CT patients, off-therapy responses were significantly higher in the 13 rs8099917 TT than in the 29 rs8099917 TG patients, with a rate of sustained virological response of 23% versus 3%, P ¼ 0.045 and of HBsAg loss of 23% versus 0%, P ¼ 0.007.…”

Section: Replysupporting

confidence: 47%

“…[2][3][4] In this respect, we reported that Hp-I is frequently detected in neurodegenerative diseases including CD and Alzheimer's disease (AD) and Hp eradication may positively influence AD manifestations at 2-and 5-year clinical endpoints, 2 thereby supporting a role for this common infection in the pathobiology of the disease. Others also found that AD patients infected by Hp tended to be more cognitively impaired, and patients with dementia have a higher risk of falls and fractures 3 ; Hp-I may also be responsible for osteoporosis.…”

Section: Replymentioning

confidence: 99%

“…Finally, activated monocytes (possibly infected with Hp due to defective autophagy resulting in Hp replication in autophagic vesicles) might also enter the brain due to BBB disruption contributing to cirrhosis-related CD development associated with falls and fractures. 3 …”

Section: Replymentioning

confidence: 99%

“…Although minimal hepatic encephalopathy plays a key role in such dysfunction, other factors, such as etiology of cirrhosis, comorbidities, or psychoactive treatments, can also be implicated. [1][2][3] Multiple factors are also involved in the risk of falling. 4 …”

Section: Replymentioning

confidence: 99%

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2013

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In this issue of HEPATOLOGY, Lampertico et al. 1 present a study of mostly hepatitis B virus (HBV) genotype D hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients treated with peginterferon (PEG-)IFN and show that hepatitis B s antigen (HBsAg) loss was significantly associated with IL28B genotype. Our group recently published a study on the association of IL28B genotype with response to PEG-IFN in HBeAg-positive CHB patients. Favorable IL28B genotypes, CC for rs12979860 and AA for rs12980275, were associated with higher rates of HBeAg seroconversion and HBsAg loss. 2 Taken together, these findings provide mounting evidence for the importance of the IL28B genotype for prediction of response to PEG-IFN in CHB, although these findings require further confirmation.There is, however, an important pitfall that should be taken into consideration. In our study, IL28B genotype distribution varied across ethnicity: 90% of Asian patients were genotyped CC, compared to 50% of non-Asians. 2 Response to PEG-IFN in CHB also depends on the HBV genotype: patients with HBV genotype A achieve higher rates of response than those with HBV genotypes B, C, or D. 3 Importantly, HBV genotypes A and D predominate in Caucasians, and nearly all south east Asian patients are infected with HBV genotypes B or C. Because IL28B genotype is associated with ethnicity, it is also associated with HBV genotype. In our study of HBeAg-positive patients, the favorable IL28B genotype was present in 42% of HBV genotype A patients, in 88%-90% of patients with HBV genotypes B or C, and in 52% of HBV genotype D patients. 2 If differences in HBV genotype distribution are ignored, analyses of the association between IL28B genotype and HBsAg loss in a cohort of patients with mixed ethnicities could result in an overrepresentation of Asian patients (with ''poor response'' HBV genotypes B or C) in the favorable CC group, and an overrepresentation of Caucasians and black Africans (with ''good response'' HBV genotype A) in the unfavorable CT/TT groups. This could result in a biased estimate of association, or failure to detect one. This issue is particularly relevant for studies conducted in countries with mixed ethnicities, such as those in Western Europe and the United States, where the HBV-infected population comprises Caucasians, Asians, and black Africans.In conclusion, the study by Lampertico et al. provides fascinating new data and urges further studies of IL28B genotype and response to PEG-IFN in CHB. However, the association of IL28B genotype distribution with that of HBV genotype may introduce an important pitfall. Therefore, we strongly recommend that future studies of IL28B in CHB be stratified by, or adjusted for, HBV genotype. Reply:We fully agree with Dr. Sonneveld et al.'s interpretation of our study 1 suggesting an interplay between response to interferon and rs12979860 polymorphisms in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B in Italy. The reason we omitted presenting data on an association be...

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Section: Replysupporting

confidence: 47%

Section: Replymentioning

confidence: 99%

Section: Replymentioning

confidence: 99%

Section: Replymentioning

confidence: 99%

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2013

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Section: Helicobacter Pylori Induced Cognitive Dysfunction Might Be Amentioning

confidence: 99%

Helicobacter pylori induced cognitive dysfunction might be associated with falls and fractures in cirrhosis

et al. 2013

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Helicobacter pylori Induced Cognitive Dysfunction Might Be Associated With Falls and Fractures in CirrhosisTo the Editor:In their prospective series, Soriano et al. 1 concluded that cognitive dysfunction (CD) is a factor associated with falls in patients with cirrhosis, and further studies are warranted to address the mechanisms implicated in this predisposition and to design preventive strategies.Apart from CD causes that can be the result of multiple issues, including the etiology of cirrhosis, mentioned by the authors, 1 Helicobacter pylori infection (Hp-I) appears to be a common denominator associated with CD-related falls and fractures and liver cirrhosis. [2][3][4] In this respect, we reported that Hp-I is frequently detected in neurodegenerative diseases including CD and Alzheimer's disease (AD) and Hp eradication may positively influence AD manifestations at 2-and 5-year clinical endpoints, 2 thereby supporting a role for this common infection in the pathobiology of the disease. Others also found that AD patients infected by Hp tended to be more cognitively impaired, and patients with dementia have a higher risk of falls and fractures 3 ; Hp-I may also be responsible for osteoporosis. Moreover, hepatitis B (HBV) and C (HCV) are among the commonest causes of liver cirrhosis worldwide 4,5 and Hp-I is strongly associated with HBV-and HCVrelated cirrhosis in Europe (Italy); Hp-I is more common in cirrhosis patients with hepatic encephalopathy (HE) than in those without, 5 and HE is not a fully reversible condition.Summarizing the aforementioned data, Hp may be involved in the pathophysiology of cirrhosis-related CD by several mechanisms, 4 such as the release of proinflammatory and vasoactive substances, involved through blood-brain barrier (BBB) disruption, in a number of vascular disorders including AD, which can lead to long-term neurologic deficits; promoting platelet-leukocyte aggregation proposed to play pathophysiologic roles in AD and liver fibrosis; producing reactive oxygen metabolites involved in the AD pathophysiology and complications of cirrhosis; or influencing the apoptotic process, an important form of cell death in AD and cirrhosis. Finally, activated monocytes (possibly infected with Hp due to defective autophagy resulting in Hp replication in autophagic vesicles) might also enter the brain due to BBB disruption contributing to cirrhosis-related CD development associated with falls and fractures. 3

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