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Biomedical subjects

Mariano Malaguarnera

Publications and source records attributed to Mariano Malaguarnera.

At least 19 recordsLinked to original sources
PubMed2006

Value and significance of new diagnostic criteria of diabetes mellitus in older people.

In 1998, the World Health Organization (WHO) accepted the diagnostic criteria proposed in 1997 by the American Diabetes Association (ADA) and confirmed that, independent of age, the fasting plasma glucose (FPG) level from and above 126mg/dl in the morning should be considered as diabetic, while subjects with FPG 110-125mg/dl have an impaired fasting glucose (IFG), compared with the normal fasting glucose (NFG) level (up to 110mg/dl). In a pool of 4492 elderly people (65-84 years), we assessed the significance and meaning of these new diagnostic criteria of diabetes. A 5-year follow-up was carried out, during which out of 4492 elderly subjects, 2750 were re-examined. As regards the diagnosis, we applied both the criteria of WHO (1985, 1998). At our first observation (1992), 13.1% were diabetic in the elderly group, if applying the WHO (1985) criteria, and 15.1% applying the ADA-WHO definitions. When re-analyzing the subjects with FPG of 126-139mg/dl after 5 years, it became evident that the diagnosis of diabetes is not stable in this group, because 50.7% of them displayed FPG<126mg/dl (14.5% IFG; 36.2% even NFG). It means that the significance of FPG and the conditions of diabetes are different in the elderly, as compared with the younger adults. Furthermore, the oral glucose tolerance test (OGTT) of 60 elderly subjects in the age range of 71-80 years, admitted in our day hospital, were considered. Among the subjects with an FPG 126-140mg/dl, the OGTT was of diabetic type in 90%, while among IFG and NFG subjects, it was in 50 and 10%, respectively. In conclusion, in elderly subjects with FPG of 126-140mg/dl, the diagnosis of diabetes is not stable and requires further confirmation.

Aged↗
PubMed2006

Effects of L-acetylcarnitine on cirrhotic patients with hepatic coma: randomized double-blind, placebo-controlled trial.

Multiple therapeutic modalities have been used to treat hepatic encephalopathy. L: -Acetylcarnitine (LAC) is a physiologically active substance that improves both the energetic and the neurotransmission profiles. LAC is able to cross the hematoencephalic barrier and reach the cerebral regions, where the acetylic group may be utilized. The aim of this work was to evaluate the efficacy of LAC in the treatment of hepatic coma in cirrhotic patients. Twenty-four suitably selected patients were enrolled in the study and, following randomization, received either LAC (n=13) or placebo (n=11). Statistically significant differences in neurological findings, as evaluated by the Glasgow Scale, as well as in ammonia serum levels and BUN were found following LAC treatment. In the placebo group we observed two cases of improved neurological findings as well as one case of improved EEG grading. In the other group we observed an improvement of neurological findings and of EEG grade in 10 and 8 subjects, respectively. Noteworthily, seven (54%) patients went from grade 4 down to grade 3, and one from grade 4 down to grade 1. The improvement in the neurological picture was evident at between 1 and 4 hr after the end of treatment, remaining until 24 hr after. No side effects were observed in our study series. Our study demonstrates that LAC administration improved neurological and biohumoral symptoms in selective cirrhotic patients with hepatic coma.

Acetylcarnitine↗
PubMed2006

Cardio-cerebrovascular complications in elderly with diabetes.

Authors have considered the prevalence of hypertension (HT), myocardial infarction (MI) and stroke (S), in elderly subjects with diabetes, impaired fasting glucose (IFG) and normal fasting glucose (NFG), respectively. A high occurrence of diabetes in elderly subjects has been found. MI and S were more frequent in diabetic group than in IFG and NFG ones. HT proved to be elevated in the total pool, especially in older olds, and with a higher prevalence among those with diabetes. A 5-year follow-up has been carried out. The index of survival for MI and S was lower in subjects with diabetes. The subjects affected by both MI and S displayed the worst index of survival in all the three categories considered, therefore, it can be stated that such an association is a determinant factor of mortality.

Aged↗
PubMed2006

Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia.

AIM: To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. METHODS: Fifty-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS: When the cachectic patients with gastro-intestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 micromol/L in free carnitine (P < 0.005), 0.04 micromol/L in long chain acylcarnitine (P < 0.05), 8.7 micromol/L in total carnitine (P < 0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2 micromol/L in free carnitine (P < 0.001), 4.60 micromol/L in short chain acylcarnitine (P < 0.001), and 0.60 micromol /L in long-chain acylcarnitine (P < 0.005) and 17.4 micromol/L in total carnitine (P < 0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 micromol/L in free carnitine (P < 0.001), 5.2 micromol /L in short-chain acylcarnitine (P < 0.001), 1.0 micromol/L in long chain acylcarnitine (P < 0.001), and 21.8 micromol/L in total carnitine (P < 0.001). CONCLUSION: Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.

Adult↗
PubMed2006

Potential role of chitotriosidase gene in nonalcoholic fatty liver disease evolution.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by steatosis and periportal and lobular inflammation. The molecular mechanisms involved in the anomalous behavior of liver cells have only partially been disclosed. Human Chitotriosidase (Chit) is a member of the chitinase family that it is mainly synthesized by activated macrophages. We investigated chitotriosidase gene expression in Kupffer cells to determine the potential implication of this enzyme in the inflammation and in the progression from uncomplicated steatosis to steatohepatitis with progressive fibrosis. METHODS: Seventy-five liver biopsies from 40 subjects with NASH, 20 with simple steatosis, and 15 controls were used to detect CHIT expression, tumor necrosis factor-alpha (TNF-alpha), alpha-smooth muscle actin (alpha-SMA), and lipid peroxidation. RESULTS: CHIT was expressed exclusively by Kupffer cells. The levels of CHIT expression were significantly higher in NASH patients than in simple steatosis patients and in the control group. In addition, we found that CHIT over-expression influenced hepatic stellate cells activation, as demonstrated by the significant correlation between CHIT and alpha-SMA expression in NASH patients. A significant correlation was observed also between CHIT, TNF-alpha and lipid peroxidation in both NASH and simple steatosis. CONCLUSION: These results suggest that CHIT over-produced by Kupffer cells may contribute to the progression of hepatic fibrosis.

Actins↗
PubMed2006

Hepatitis C virus in elderly cancer patients.

BACKGROUND: There are few studies about the relationship between HCV and the development of other tumors. We consider the prevalence of HCV infection in elderly cancer patients who have tumors different from that in hepatocellular carcinoma and non-Hodgkin's lymphoma. METHODS: We evaluated the prevalence of HCV infection in 236 elderly cancer patients in comparison with 300 elderly volunteers. Cancer patients presented a variety of tumors other than hepatocarcinoma and lymphoma, namely, colorectal (n=66), breast (n=44), bladder (n=40), prostate (n=30), lung (n=22), kidney (n=15), pancreatic (n=6), thyroid (n=5), cervical (n=4), melanoma (n=3) and vaginal (n=1). RESULTS: Among the 236 elderly cancer patients, 87 were positive for HCV antibodies (36%) and, among the 300 elderly patients, 32 were positive (10%). A comparison between the two groups revealed a statistically significant difference (p<0.001) between patients with kidney cancer, bladder cancer or prostate cancer, and the control group. CONCLUSIONS: The high anti-HCV prevalence in elderly cancer patients may be due to several mechanisms. These patients are more prone to acquire an HCV infection because of their frequent hospitalizations and the immunological changes in patients with tumors may lower their threshold for HCV infection.

Journal Article↗
PubMed2006

The management of tumor lysis syndrome.

The manifestation of tumor lysis syndrome (TLS) occurs when the destruction of tumor cells releases breakdown products that overwhelm the excretory mechanisms of the body. A cardinal sign is hyperuricemia, leading to uric acid nephropathy. Other signs are hyperkalemia, hyperphosphatemia and secondary hypocalcemia. Conventional management of TLS consists of aggressive intravenous hydration, diuretic therapy, urinary alkalization, and inhibition of urate production by high-dose allopurinol. Urate oxidase has been used in the management of patients at risk for TLS and recently the recombinant urate oxidase rasburicase was developed. Several data indicate that rasburicase is effective and well tolerated in the prevention and treatment of chemotherapy-induced hyperuricemia. Treatment options of hyperkalemia include sodium polystyrene sulfonate, hypertonic glucose and insulin, loop diuretics, and bicarbonate. Treatment of hyperphosphatemia reduces dietary phosphate intake and includes phosphate binders such as aluminum hydroxide and aluminum carbonate. When recurrent hypocalcemia is present, a continuous intravenous infusion of calcium gluconate can be initiated. Hemodialysis should be considered for every patient with excessively elevated uric acid, phosphate and/or potassium and in those patients with acute renal failure to control urinary volume and manage uremia.

Acute Kidney Injury↗
PubMed2006

New possibilities of treatment for panic attacks in elderly patients: escitalopram versus citalopram.

PURPOSE: Panic attacks may represent additional therapeutic problems in the elderly. The utility of citalopram in panic attacks has been widely investigated. Here, we compare the efficacy and safety of citalopram, with its S-enantiomer escitalopram at half dosage as to citalopram, in elderly patients who have panic attacks. METHODS: This was an open community-based study. Forty patients who have panic attacks, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, were enrolled. Fifty percent of the patients were assigned for 8 weeks' treatment with escitalopram, and the remaining 50% were assigned to treatment with citalopram. The primary outcome measure was the weekly rate of panic attacks. The secondary outcome measures were the Hamilton scale for anxiety and depression and the Cooper Disability Scale. Analysis of variance by repeated measures was applied to calculate differences between groups. RESULTS: A similar decrease in weekly rate of panic attacks, in the scores of Hamilton Scale for anxiety and depression and in the Cooper Disability Scale scores, was observed in both groups after 8 weeks, but a significant variation of outcome measures from baseline was observed already after 2 weeks in the escitalopram group (P < 0.001) and only after 4 weeks in the citalopram group (P < 0.01). CONCLUSIONS: Escitalopram could be considered among the drugs of first choice in elderly patients with panic attacks because of its good efficacy and safety and for the advantage of reducing the total dose and of a more rapid onset of action as compared with citalopram, although further studies are needed to confirm these results.

Aged↗
PubMed2006

Interleukin-18 and transforming growth factor-beta 1 plasma levels in Alzheimer's disease and vascular dementia.

Inflammation has been involved in the development of dementia in cerebrovascular diseases. To investigate the cellular activation of the peripheral immune system in patients with Alzheimer's disease (AD) and vascular dementia (VaD), we determined the presence of IL-18 and TGF-beta1 in the plasma by using ELISA. The levels of IL-18 and TGF-beta1 were significantly elevated in patients with AD and VaD compared to non-demented, age-matched subjects. We found an inverse correlation between the levels of IL-18 and TGF-beta1 in AD patients. In VaD patients, the correlation between IL-18 and TGF-beta1 reached a borderline positive value. Whereas, in the non-demented, age-matched subjects, a positive correlation between IL-18 and TGF-beta1 levels was observed. These findings indicate that IL-18 and TGF-beta1 elevation is associated with AD and VaD patients, confirming that the immune system might exert a remarkable role in the development and progression of neurodegenerative disorders. Moreover, as different modifications were detected in the patients affected by AD and VaD, we propose that IL-18 and TGF-beta1 plasma levels might represent possible differential biomarkers.

Aged↗
PubMed2006

Chitotriosidase and inflammatory mediator levels in Alzheimer's disease and cerebrovascular dementia.

Inflammation has been reported to be involved in the pathogenesis of cerebrovascular dementias (CvDs). This study investigated the involvement of Chitotriosidase (ChT), a chinolitic enzyme mainly produced by activated macrophages, in the pathophysiology of Alzheimer's disease (AD) and ischemic CvD. In addition, the levels of interleukin (IL)-16, IL-18, transforming growth factor (TGF)-beta1 and superoxide anion (O2(-)) were determined to evaluate the relationship between ChT levels, these cytokines and oxidative stress in both AD and ischemic CvD patients. The levels of ChT and IL-16, IL-18, and TGF-beta1 mRNA were investigated using quantitative real-time polymerase chain reaction on macrophages of peripheral blood of 40 patients with AD, 40 patients with ischemic CvD and 40 non-demented age-matched subjects. The results show that ChT, IL-16 and O2(-) levels significantly increased in ischemic CvD patients compared with AD patients and were significantly and positively correlated with IL-18 and O2(-). The production of IL-18 was increased in both AD and ischemic CvD patients. TGF-beta1 expression was higher in AD patients and was inversely correlated with the expression of ChT, IL-16 and IL-18, respectively. In non-demented age-matched subjects no significant changes in ChT and IL-16, IL-18, and TGF-beta1 expression were found. Our results indicate that ChT, IL-16, IL-18 and TGF-beta1 are increased in ischemic CvD and AD, confirming that the immune system may play an important role in the development and progression of neurodegenerative disorders. In addition, the present findings suggest that ChT could also play a crucial role in pathological conditions such as CvD in which the inflammatory process is activated.

Aged↗
PubMed2005

Effects of L-carnitine in patients with hepatic encephalopathy.

AIM: To evaluate the influence of L-carnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy (HE). METHODS: One hundred and fifty patients (10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection, 21 patients with cryptogenetic cirrhosis) meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine (2 g twice a day) or into group B receiving placebo in double blind. RESULTS: At the end of the study period, a significant decrease in NH4 fasting serum levels was found in patients with hepatic encephalopathy (P<0.05) after the treatment with levocarnitine (LC). Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy (P<0.05). CONCLUSION: Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.

Adult↗
PubMed2005

The chromogranin-A (CgA) in prostate cancer.

Prostate cancer is one of the most frequent tumors in men. The neuroendocrine differentiation in prostate cancer has become more widely recognized and has attracted considerable attention as a potentially new finding with major diagnostic, prognostic and therapeutic implications. We investigated the role of the serum concentrations of CgA in a group of 57 patients with prostate cancer and in 61 elderly subjects with benign prostate hyperplasia (BPH). Neuron-specific enolase (NSE) is the most frequently employed marker to detect neuroendocrine features. Serum prostate-specific antigen (PSA), CgA and NSE levels were determined. Comparing prostate cancer group versus BPH group, the CgA level difference was 63.00 ng/ml (p<0.0001) and the PSA level difference was 50.86 mcg/ml (p<0.0001). Between prostate cancer group and control group the CgA level difference was 94.3 ng/ml (p<0.0001), the PSA level difference was 52.91 mcg/ml (p<0.0001), and the NSE level difference was 1.34 microg/l (p<0.0001). Patients with higher CgA levels had poorer prognosis and survival, compared to those with lower CgA levels. These results support the concept that serum CgA level determination before treatment is a potential prognostic factor for prostate cancer.

Adenocarcinoma↗
PubMed2005

Heme oxygenase-1 levels and oxidative stress-related parameters in non-alcoholic fatty liver disease patients.

BACKGROUND/AIMS: Non-alcoholic steatohepatitis (NASH) is a disorder that is histologically characterized by macrovesicular steatosis and lobular hepatitis with necrosis or ballooning degeneration and fibrosis. NASH can range from a benign condition to end-stage liver disease. The mechanisms promoting transition from steatosis to NASH appear to involve multiple cellular adaptations to the oxidative stress occurring when fatty acid metabolism is altered. We evaluated the relationship between lipid peroxidation and other oxidative stress biomarkers with changes in expression of heme oxygenase-1 (HO-1) in human hepatic steatosis ranging from simple steatosis to NASH. METHODS: HO-1 expression, lipid peroxidation, ferritin and GSH levels were assayed from liver biopsies obtained from 60 subjects: 35 with NASH, 15 with simple steatosis and 10 controls. RESULTS: The HO-1 expression was significantly increased in NASH patients and the increase reflected the severity of the disease. A significant correlation was observed between the increased levels of HO-1 and ferritin, and between the increased levels of HO-1 and lipid peroxidation. Moreover, NASH patients with lower levels of GSH exhibited higher expression of HO-1. CONCLUSIONS: The induction of HO-1 is an adaptive response against oxidative damage elicited by lipid peroxidation and it may be critical in the progression of the disease.

Adult↗
PubMed2005

Serum carnitine levels in patients with tumoral cachexia.

BACKGROUND: Cachexia is a serious complication of many cancers that is common in cancer and AIDS patients. However, the key factors and mechanisms involved in the development of cachexia are not yet understood. There is little data currently available regarding carnitine metabolism in patients with neoplasm and cachexia. METHODS: Forty-six neoplastic patients with different localizations of their primary disease gave signed, informed consent before enrolling in the present study. They underwent routine laboratory investigation, including examination of the levels of the various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, soluble acid acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 30 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS: In the comparison of serum plasma carnitine of cachectic patients versus controls, the difference in free carnitine was - 8.20 micromol/L (p=0.000); the difference in short-chain acylcarnitine - 2.60 micromol/L (p=0.029); the difference in soluble acid carnitine - 10.80 micromol/L (p=0.000); the difference in long-chain acylcarnitine - 0.40 micromol/L (p=0.036); and the difference in total carnitine -11.20 micromol/L (p=0.000). In the comparison of serum plasma carnitine of cachectic versus neoplastic patients in good nutritional status, the difference in free carnitine was -5.80 micromol/L (p=0.006); the difference in soluble acid carnitine - 7.20 micromol/L (p=0.000); and the difference in total carnitine - 7.50 micromol/L (p=0.000). CONCLUSION: Our study showed that, in the multifactorial pathogenesis of cachexia, the low serum levels of carnitine in terminal neoplastic patients, which are due to a decreased dietary intake as well as to an impaired endogenous synthesis of this substance, could play an important role. These low serum carnitine levels may also contribute to the development of cachexia in cancer patients.

Journal Article↗
PubMed2004

An evaluation of efficacy and safety of reboxetine in elderly patients affected by "retarded" post-stroke depression. A random, placebo-controlled study.

Depression occurs frequently in post-stroke patients and appears to be associated with an impairment in their rehabilitation and functional recovery. Although selective serotonin reuptake inhibitors (SSRI) are often used in post-stroke depression (PSD), it has been observed that only a subset of patients is responsive to this treatment. Other patients respond to tricyclic antidepressants or MAO inhibitors, which, however, may not have a favorable profile of safety and tolerability in post-stroke patients. In this double-blinded, placebo-controlled study, we evaluated the efficacy and tolerability of the noradrenaline reuptake inhibitor, reboxetine, in a subset of PSD patients classified as affected by "retarded" depression. Reboxetine (4 mg, twice daily, for 16 weeks) was administered to patients that developed depression after a single ischaemic or hemorrhagic stroke. We assessed the severity of depressive symptoms by the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). HDRS and BDI scores (mean+/-S.D.) at baseline were, respectively, 24+/-1.31 and 19.87+/-1.46 in the placebo group, 24.06+/-1.52 and 20.56+/-2.16 in the reboxetine group. After 16 weeks, HDRS and BDI mean scores were respectively 22.73+/-2.4 and 18.4+/-3.33 in the placebo group, 9.26+/-2.15 and 8.06+/-3.43 in the reboxetine group [p<0.01 versus the respective baseline (paired t-test); (#)p<0.01 versus retarded depressed patients treated with placebo (one-way analysis of variance (ANOVA) applied to the difference from baseline, associated with Dunnett's t-test to isolate the differences)]. Reboxetine showed a good efficacy, safety and tolerability in PSD patients affected by "retarded" depression. We conclude that reboxetine is well tolerated and may be a useful therapeutic option in PSD patients with "retarded" depression.

Aged↗
PubMed2004

Ultrasound evaluation of centenarians' gallbladder.

Background: Ultrasound (US) examination of gallbladder is considered to be reliable, both in morphological and functional evaluation. We used US to study the gallbladder of a series of centenarians in order to show the characteristics of this organ in these subjects. We then compared the data obtained with two control populations omposed of elderly and adult subjects, respectively. Methods: US examination was done after an overnight fast and after emptying the gallbladder at 15-min intervals for a period of 90 min. To induce emptying of the gallbladder, we chose a semisolid meal with a small caloric value (370 kcal). The following parameters were evaluated: fasting gallbladder volume (in milliliters) before administration of the meal (considered to be 100%); gallbladder emptying (according to the formula: fasting gallbladder volume minus post-meal gallbladder volume at 10-min intervals divided by fasting gallbladder volume: the result of this operation was multiplied by 100); gallbladder motor functions, such as ejection volume (ml), is considered as the difference between fasting gallbladder volume and residual volume; ejection fraction (%), considered as the difference between fasting gallbladder volume and residual volume, is expressed as percentage fasting volume; and ejection rate (%/min) is calculated by dividing ejection fraction by time requested to reach the residual volume. Results: We found a common bile duct diameter that was significantly higher in centenarians than in the elderly and adults. Gallbladder wall thickness was significantly higher in centenarians than in adults. We also found substantially significant differences between centenarians with and without gallstones and elderly and adult subjects in the following parameters: mean gallbladder volume (reduced), residual volume (reduced), ejection volume (reduced) and ejection rate (reduced). The differences were not significant for the ejection fraction, and they were slightly reduced in centenarians compared to the other groups. There was a negative correlation between age and axial length (transverse diameter), age and width and age and common bile duct (CBD) diameter in the elderly group only. Conclusions: The study of gallbladder function in elderly people and centenarians is important because this parameter is related to the quality of digestion and absorption of many alimentary substances as well as to the formation of cholesterol gallstones. We found that gallbladder functions in centenarians are almost normal with respect to the elderly and adults. Contractility was higher than in our elderly sample. This fact ensures a correct concentration of bile salts and a good intestinal transit rate. It may represent one of the factors allowing for good digestive function in these subjects, which contributes to their health status.

Journal Article↗
PubMed2004

Helicobacter pylori and Alzheimer's disease: a possible link.

BACKGROUND: Although serological findings indicate the presence of a relationship between Helicobacter pylori (HP) and vascular disease, no data have been reported about a possible association of HP with dementia. The aim of the present study was to determine whether chronic HP infection might play a role in Alzheimer's disease (AD). METHODS: Plasma homocysteine level, serum folate and vitamin B(12) concentrations, plasma pyridoxal phosphate level, IgG and IgA antibodies to HP, and C-reactive protein (CRP) were determined in 30 AD patients, 30 patients affected by vascular dementia (VaD), and 30 control subjects. All patients and control subjects were matched for age, educational level, and nutritional and socioeconomic status. None of the subjects had a history of chronic gastritis, peptic ulcer, gastric cancer, or major abdominal surgery. RESULTS: HP-IgG level was significantly increased in VaD patients as compared to controls and AD patients, while AD patients had HP-IgG levels higher than those of normal controls. HP-IgA levels were equally increased in both VaD and AD patients. CRP was higher in AD patients than in VaD patients and controls, although CRP levels in VaD patients were also significantly increased. CONCLUSIONS: The present study found an association between HP infection and AD. The question remains as to whether this association is due to the ubiquity of HP, or whether it contributes to the neuroinflammatory process in AD. The relationship between HP and AD, if confirmed by additional studies with a greater number of patients, may have important clinical and therapeutic implications.

Journal Article↗