Giovanni Gallotta

Plasma Folate, Vitamin B12, and Total Homocysteine and Homozygosity for the C677T Mutation of the 5,10-Methylene Tetrahydrofolate Reductase Gene in Patients with Alzheimer’s Dementia

Background: Elevated total plasma homocysteine (tHcy) levels are considered a risk factor for cerebrovascular disease and may also play an important role in the pathogenesis of Alzheimer’s disease (AD). High values of plasma tHcy and low levels of vitamin B12 and folate are frequently present in AD patients. Moreover, the homozygous mutation (C677T) of the methylene tetrahydrofolate reductase (MTHFR) gene, related to a thermolabile type of the encoded enzyme, causes hyperhomocysteinemia by reducing the 5-methyltetrahydrofolate availability. Objective: The aim of the study was to investigate plasma levels of folate, vitamin B12 and tHcy in patients with AD. These values were also related to the severity and the duration of the disease and to the possible role of the MTHFR genotype (C677T). Method: Plasma tHcy levels, homozygosity for the C677T mutation of the MTHFR gene, and folate and vitamin B12 plasma levels were evaluated in 74 patients with AD (45 men, 29 women, mean age 68 years) and in 74 healthy matched controls (42 men, 32 women, mean age 68 years). Results: AD patients had higher mean (± SD) plasma levels of tHcy (20.9 ± 15 µmol/l compared to 11.8 ± 5 µmol/l, p < 0.001) and lower mean plasma folate (5.7 ± 2.1 ng/ml compared to 8.5 ± 3.2 ng/ml, p < 0.001) and vitamin B12 (491 ± 144 pmol/l compared to 780 ± 211 pmol/l, p < 0.001) concentrations. Homozygosity for the C677T mutation of the MTHFR gene had a similar prevalence among controls (18%) and AD patients (20%). Homozygous AD patients (n = 15) had higher plasma tHcy values than nonhomozygotes, in spite of similar mean plasma folate and vitamin B12 levels. This difference in plasma tHcy levels was not observed in controls. Patients with levels of plasma tHcy above and of plasma folate below the normal limits were more frequent in the homozygous AD group. The duration of the disease correlated with plasma levels of tHcy (r = +0.832, p < 0.001), plasma folate (r = –0.580, p < 0.05), and vitamin B12 (r = –0.460, p < 0.05). However, when all the data were corrected for age, serum creatinine levels, and duration of the disease, mean plasma tHcy, folate, and vitamin B12 levels were not statistically different between controls and AD patients. Conclusions: Our data suggest that rather than a risk factor for AD, hyperhomocysteinemia is related to its progression and increasing severity. This might be particularly relevant in homozygotes for the C677T mutation of the MTHFR gene and supports the possible need for continuous supplements in this setting.

Changes in middle cerebral artery blood velocity in uremic patients after hemodialysis.

Background and Purpose Strokes are a frequent complication in uremic patients on dialysis. We wanted to evaluate the effect of this treatment on cerebral hemodynamic parameters, particularly those of patients with carotid stenosis, who are at higher risk for atherothrombotic ischemic events. Methods We used transcranial Doppler ultrasonography to evaluate blood velocity of the middle cerebral artery in 18 uremic patients before and after hemodialysis. Carotid stenosis was evaluated by echo-Doppler investigation. Six patients were also studied before and after recombinant human erythropoietin treatment. Results Dialysis treatment decreased mean blood velocity in all patients (p<0.001). Eight of 18 patients (44%) with mild (16–50%), moderate (51–80%), or severe (>80%) carotid stenosis had lower velocity than patients with normal carotid arteries (p<0.01), and they experienced a further decrease to even lower levels after hemodialysis (p<0.05). In patients treated with recombinant human erythropoietin, hematocrit increased from 28±8% to 37±5% (p<0.001), and blood velocity had a further decrease by 11%. All changes were associated with modifications toward normality of pH, Paco2, and hematocrit. Conclusions Transcranial Doppler ultrasonography represents a useful method for monitoring cerebral circulation of uremic patients, especially of those at possible risk for ischemia.

Prevalence of Peripheral Arterial Disease in an Elderly Rural Population of Southern Italy

Blood pressure was measured at the posterior tibial artery by Doppler ultrasonography in 440 elderly subjects (205 men and 235 women) living in a rural community of Southern Italy, together with the evaluation of traditional risk factors for cardiovascular disease. An ankle/arm systolic pressure ratio below 0.90 was considered as a definite pathological sign of peripheral arterial disease (PAD). About 10% of both men and women had a value below 0.90. Elderly subjects with PAD had higher serum triglyceride levels and a higher ratio between the cholesterol content in atherogenic (VLDL + LDL) versus non-atherogenic (HDL) lipoproteins than subjects free of PAD. The mean blood pressure was also higher in patients with PAD. The prevalence of PAD was much lower than what we have observed in institutionalized old subjects in Southern Italy.

Plasma lipids and geriatric assessment in a very aged population of South Italy

A very old population of a rural area of Southern Italy with a mean age of 87 years was investigated in order to evaluate serum lipid levels and their possible association with health conditions, such as mental status, social behaviour and physical autonomy. Among 101 subjects with ages above 82 years, 73 were investigated (participation rate 72%, 31 men and 42 women). Mean +/- SD serum cholesterol level was 199 +/- 36 and 210 +/- 40 mg/dl and mean serum triglyceride level was 107 +/- 43 and 148 +/- 74 mg/dl (P less than 0.05) in men and women, respectively. Mean high density lipoprotein (HDL)-cholesterol level was 49 mg/dl in both sexes. All subjects were investigated by means of geriatric and neuropsychometric scales such as Sandoz Clinical Assessment Geriatric Scale (SCAGS), Hachinski Dementia Scale (HDS), Plutchik Geriatric Rating Scale (PGRS) and Indexes of Activity of Daily Living (ADL). When subjects were divided into 3 groups according to levels of serum lipids, HDL-cholesterol appeared to be better related to clinical conditions than total serum cholesterol: the group with the higher HDL-cholesterol level presented better scores at all the administered assessment scales when compared to the groups with lower and modal levels (P range between less than 0.05 and less than 0.001). Subjects in the higher serum cholesterol group presented better scores at PGRS only (P less than 0.01). No relation was observed between serum total triglyceride levels and geriatric assessment scores.

Role of functional performance in diagnosis of dementia in elderly people with low educational level living in Southern Italy

Background and aims: Diagnosis of dementia is often difficult in subjects with low educational level. Our aim was to evaluate the role of functional performance and the possibility of preferring scores of activities of daily living (ADL) and instrumental activities of daily living (IADL) in screening elderly people for diagnosis of dementia in a rural population of Southern Italy with a very high percentage of non-educated subjects. Methods: a random sample of 300 residents, out of 1089 subjects over 60 years of age living in San Marcellino (Caserta, Campania), received door-to-door visit for information about their medical history, with clinical evaluation of general geriatric conditions, including the cumulative illness rating scale (CIRS). Dementia was diagnosed if subjects had a Clinical Dementia Rating score (CDR) ≥ 1 and according to the criteria of DSM-IV, but not according to scores on the Mini Mental State Examination (MMSE), ADL and IADL. Two hundred and nineteen normal subjects (NS) and 75 patients with dementia (DP) were evaluated. Results: in NS, their mean age- and education-corrected MMSE score was 22.15 (lower than the normal cut-off value of 23.8) and 12.60 in DP (p<0.0001). In NS, the mean ADL score was higher than in DP (5.53 vs 2.64, p<0.0001; only age was correlated with ADL scores (coeff=− 0.44, t=− 4.557, p<0.0001). Assuming age as covariate, ADL scores highly differentiated DP from NS (F(1, 289)=26.083, p<0.0001). In both sexes, mean IADL scores were higher in NS than in DP (4.46 vs 1.80 in men, p<0.0001); 6.85 vs 2.31 in women, p<0.0001. Age and education did not influence IADL scores in men, but age greatly affected performance in women. IADL scores clearly differentiated NS from DP. In NS, a positive correlation was evident between ADL and IADL scores (r=0.234, p<0.0005, but neither scores correlated with the MMSE scores, even when correlation was performed separately for men and women. In DP, a strong correlation was observed between ADL and IADL scores (r=0.709, p<0.0001 and significant correlations were also evident between the scores of MMSE and both ADL (r=0.492,p<0.0001) and IADL (r=0.398, p<0.0004). Conclusions: in a rural community with a high prevalence of non-educated subjects, cognitive impairment is related to education, whereas independent functioning is limited mainly to age and not to cognition, if the latter remains (relatively) unimpaired. These results point to the importance of an “ecological” approach to the evaluation of elderly people, particularly those living in small rural communities, where education and the social environment may give rise to difficulties in diagnosis of dementia. The assessment of functional autonomy by ADL and IADL scales may be a better screening tool in diagnosing dementia than the MMSE scores.

Cerebrovascular Reactivity by Transcranial Doppler Ultrasonography in Insulin-Dependent Diabetic Patients

Cerebrovascular reserve capacity (CVRC) was investigated in 13 insulin-dependent diabetic (IDDM) patients with clinical microangiopathy and in 12 healthy subjects. CVRC was assessed by transcranial Do

Hemostatic variables in homozygous familial hypercholesterolemia. Effect of regular plasma cholesterol removal by low density lipoprotein apheresis.

Plasma levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) and the in vitro ability of platelets to aggregate and of monocytes to express procoagulant (tissue factor) activity (PCA) were evaluated in five patients who are homozygous for familial hypercholesterolemia (FH) before and after a single and a regular 5-month cholesterol removal by low density lipoprotein (LDL) apheresis. The biweekly procedure resulted in a 25% to 30% reduction (approximately 150 mg/dl) in total and LDL cholesterol (both were greater than 550 mg/dl at the beginning of the study). The basal levels of t-PA antigen and fibrinolytic activity before and after 10 minutes of venous stasis, basal PAI activity, and PAI-1 antigen were comparable to controls and were not affected by LDL apheresis. Likewise, regardless of the cholesterol removal, the PCA of freshly isolated monocytes and that of monocytes incubated with lipopolysaccharide did not differ from control values. Finally, the pre-apheresis sensitivity of platelets to adenosine diphosphate, arachidonic acid, and collagen was 1.5 to 2 times the normal value. This ratio was unchanged throughout the 5-month procedure. We conclude that fibrinolysis and monocyte PCA are normal in FH patients, whereas platelet aggregation is abnormally high, and none of these parameters is significantly affected by a 25% to 30% reduction in total and LDL cholesterol by LDL apheresis. Furthermore, our data suggest that removal of cholesterol from plasma by LDL apheresis is important for gaining insight into the mechanisms involved in the ischemic complications of arteriosclerosis in FH patients.

Mental status impairment in patients with West Haven grade zero hepatic encephalopathy: the role of HCV infection

BackgroundIn patients with cirrhosis, subclinical hepatic encephalopathy, which negatively affects the activity of daily living, is often unidentified. In a multicenter observational study, we investigated the possibility of detecting minimal neurological changes consistent with subclinical hepatic encephalopathy by using the Trail Making Test in a cohort of patients with liver cirrhosis at hospital admission.MethodsSeventy-seven consecutive patients with liver cirrhosis were studied (mean age, 69.5 ± 9.1; 95% confidence interval, 67.5–71.6 years). In all patients, possible encephalopathy was investigated according to the West Haven criteria. All those free of any sign of encephalopathy (West Haven 0) were also studied by the Trail Making Test forms A and B. The Child-Pugh score was determined in all patients, and results were compared with the West Haven stage. Exclusion criteria were use of benzodiazepine, beta adrenergic blockers, alcohol, or antiepileptic drugs, or coexistence of depression, dementia, Parkinson’s disease, or chronic or acute cerebral vasculopathy.ResultsOf the 77 patients, 44 (57.1%, 23 men and 21 women) had West Haven score 0, but among these, 26 (59.1%) were diagnosed with mental impairment likely linked to minimal hepatic encephalopathy. Severity of liver disease correlated with the presence of likely minimal hepatic encephalopathy, because the prevalence of abnormal Trail Making Test results increased from 22.2% in Child-Pugh A, to 63.4% and 74.0% in Child-Pugh B and C, respectively.ConclusionsThe investigation of patients with cirrhosis by the West Haven test is not sufficient to identify subclinical forms of encephalopathy. The Trail Making Test (a simple, inexpensive test) in our series evidenced poor psychometric performance in more than half of the patients who were free of manifest encephalopathy. Subclinical hepatic encephalopathy was present mostly in patients with HCV-related cirrhosis. Detecting minimal hepatic encephalopathy in patients with cirrhosis may help improve their quality of life.

Prevalence of Peripheral Arterial Disease and Related Risk Factors in Elderly Institutionalized Subjects

Blood pressure was measured at the posterior tibial artery by Doppler ultrasonography in 124 elderly subjects (37 men and 87 women) living in two retirement homes in Naples (Italy). Ankle-to-arm systolic pressure ratios below 0.97 and 0.90 was considered as a probable and definite pathological sign of peripheral arterial disease, respectively. Half of the subjects (48% of men and 51% of women) gave a value below 0.97, while a third (35% of men and 33% of women) had a value below 0.90. By multiple regression analysis, mean blood pressure, plasma cholesterol levels and cigarette smoking were all negatively correlated with ankle systolic pressure values with a progressively lower significance. Most of the patients with pathological Doppler examination were asymptomatic at a questionnaire for intermittent claudication.

Fronto-temporal dementia presenting as Geschwind's syndrome

Geschwind described a syndrome (Geschwind syndrome, GS) in patients with temporal lobe epilepsy, characterized by sexual behavioural disorders, hyper-religiosity, hypergraphia and viscosity. In this report we describe a patient affected by fronto-temporal dementia (FTD), who showed all the personality changes of GS without having epilepsy, and suggest that clinicians should be aware of several other features in FTD, such as hyposexuality and hypergraphia, which are usually not noted during the diagnostic evaluation.