Francesco Bonetti

Discharge diagnosis and comorbidity profile in hospitalized older patients with dementia.

The aim of this study was to investigate the principal discharge diagnosis and related comorbidity in hospitalized older patients affected by dementia.

Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer's disease or vascular dementia: a case-control study.

BackgroundIn central nervous system cholesterol cannot be degraded but is secreted into circulation predominantly in the form of its polar metabolite 24(S)-hydroxycholesterol (24S-OH-Chol). Some studies suggested an association between 24S-OH-Chol metabolism and different neurological diseases including dementia. A possible decrease in 24S-OH-Chol plasma levels has been reported late onset Alzheimers disease (LOAD) and vascular dementia (VD), but results of previous studies are partially contradictory.MethodsBy high-speed liquid chromatography/tandem mass spectrometry we evaluated the plasma levels of 24S-OH-Chol in a sample of 160 older individuals: 60 patients with LOAD, 35 patients with VD, 25 subjects affected by cognitive impairment no-dementia (CIND), and 40 (144 for genetics study) cognitively normal Controls. We also investigated the possible association between PPARgamma Pro12Ala polymorphism and dementia or 24S-OH-Chol levels.ResultsCompared with Controls, plasma 24S-OH-Chol levels were higher in LOAD and lower in VD; a slight not-significant increase in CIND was observed (ANOVA p: 0.001). A positive correlation between 24S-OH-Chol/TC ratio and plasma C reactive protein (CRP) levels was found in the whole sample, independent of possible confounders (multiple regression p: 0.04; r2: 0.10). This correlation was strong in LOAD (r: 0.39), still present in CIND (r: 0.20), but was absent in VD patients (r: 0.08). The PPARgamma Pro12Ala polymorphism was not associated with the diagnosis of LOAD, VD, or CIND; no correlation emerged between the Ala allele and 24S-OH-Chol plasma levels.ConclusionsOur results suggest that plasma 24S-OH-Chol levels might be increased in the first stages of LOAD, and this phenomenon might be related with systemic inflammation. The finding of lower 24S-OH-Chol concentrations in VD might be related with a more advanced stage of VD compared with LOAD in our sample, and/or to different pathogenetic mechanisms and evolution of these two forms of dementia.

Subsyndromal Delirium and Its Determinants in Elderly Patients Hospitalized for Acute Medical Illness

BACKGROUND In older individuals, acute medical illnesses and admission to hospital are often associated with a deterioration of cognitive status, also in the absence of dementia and full-blown delirium. We evaluated the prevalence of subsyndromal delirium (SSD) and its correlates in a sample of elderly medical inpatients. METHODS From 763 consecutive inpatients, 325 participants with known dementia or delirium were excluded, whereas 438 (mean age: 80.6 years; female participants: 60.1%) were enrolled. SSD was diagnosed within 48 hour from admission, when at least two DSM-IV delirium criteria including disorientation, attention or memory deficit, altered level of consciousness, or perceptual disturbances were present. Cognitive performance was evaluated by Mini Mental Status Examination (MMSE). General, clinical, and laboratory parameters were also registered. RESULTS One hundred and sixty-six patients (37%) had SSD. Compared with controls, SSD patients were older individuals, had less formal education, higher comorbidity, lower hemoglobin/lymphocytes counts, and higher creatinine levels. A trend toward higher prevalence of previous stroke and widowhood was observed. A MMSE score of less than 24/30 identified SSD with 88% sensitivity and 78% specificity. In SSD patients, MMSE independently correlated with years of education, high-sensitivity C reactive protein levels, and O2 arterial saturation (model adjusted r (2) = 0.30, p = .001); conversely, only years of education were associated with MMSE in controls (adjusted r (2) = 0.06, p = .01). CONCLUSIONS Our data suggest that SSD is common in hospitalized older medical inpatients, and low MMSE score might be useful for identification of participants at risk of SSD. Current inflammatory response and reduced O2 arterial saturation were the only independent determinants of cognitive performance in SSD patients.

The relationship between hyperhomocysteinemia and neurodegeneration.

Homocysteine (Hcy) is a key junction in methionine metabolism. In inherited forms of hyperhomocysteinemia patients develop early vascular damage and cognitive decline. Hyperhomocysteinemia is a common consequence of dietary, behavioral and pathological conditions and is epidemiologically related to different diseases, among them neurodegenerative ones are receiving progressively more attention in the last years. Several detrimental mechanisms that see in Hcy a possible promoter seem to be implicated in neurodegeneration (protein structural and functional modifications, oxidative stress, cellular metabolic derangements, epigenetic modifications, pathological aggregates deposition, endothelial damage and atherothrombosis). Interventional studies exploring B group vitamins administration in terms of prevention of Hcy-related cognitive decline and cerebrovascular involvement have shown scant results. In this review, current and possible alternative/complementary approaches are discussed.

Cognitive Status According to Homocysteine and B‐Group Vitamins in Elderly Adults

To determine the association between hyperhomocysteinemia and cognitive function, taking into account the effect of B group vitamin (BGV) deficiency.

Lower Plasma Klotho Concentrations Are Associated with Vascular Dementia but Not Late-Onset Alzheimer’s Disease

Background: The protein Klotho is involved in biological processes related to longevity, cardiovascular health, and cognition. Serum Klotho levels have been associated with better cognition in animal models; moreover, lower Klotho concentrations in cerebrospinal fluid from subjects with late-onset Alzheimer’s disease (LOAD) have been reported. Objective: Our study aimed to examine the possible relationship between Klotho plasma concentrations and cognitive status in the elderly. Methods: We evaluated plasma Klotho levels in a sample of 320 elderly patients admitted to a Memory Clinic. Four groups of subjects were enrolled, including cognitively intact individuals complaining about memory loss (controls) and patients affected by LOAD, mild cognitive impairment, or vascular dementia (VD). The sample was stratified by plasma Klotho tertiles. Results: Lower levels of plasma Klotho (1st tertile) were associated with older age, higher prevalence of VD, single/multiple lacunar infarcts and leukoaraiosis, coronary heart disease and stroke, and higher levels of creatinine, homocysteine, and high-sensitivity C-reactive protein. On multivariate logistic regression analysis, the risk of VD was 3- and 4-fold in subjects belonging to the 1st tertile (≤514.8 pg/mL, OR 3.54, 95% CI 1.05–11.93) and 2nd tertile (> 514.8, < 659.1 pg/mL, OR 4.28, 95% CI 1.30–14.06) compared to the 3rd tertile (≥659.1 pg/mL). A significantly increased VD risk was found for Klotho values < 680 pg/mL. Conclusion: In a sample of elderly individuals, we found a significant association between low plasma Klotho levels and VD, but not LOAD. This finding suggests that, although these 2 forms of dementia might overlap, some physiopathological mechanisms related to VD and LOAD remain distinct.

The Role of B Group Vitamins and Choline in Cognition and Brain Aging

Abstract Brain aging is a balance between homeostatic processes and harmful interactions with the environment. Each individual has a unique aging path. Healthy neurological aging requires maintenance of normal brain functioning and prevention of neuronal damage. Diet is a cornerstone of disease prevention and health promotion. B group vitamins (BGVs) and choline are micronutrients that share a key role in multiple metabolic pathways related to the nervous system’s structural and functional integrity. Almost all BGVs show clinically relevant neurological manifestations in case of insufficient dietary intake. BGVs and choline seem to have a role in optimizing brain energy metabolism, containing oxidative stress and inflammation, maintaining deoxyribonucleic acid stability and regulation of gene expression, modulating neurotransmission, and preventing vascular damage. A possible role in neurodegenerative disease prevention has been hypothesized. BGV deficiency-related disturbances in homocysteine metabolism result in hyperhomocysteinemia, a plausible contributor in many of these processes.

Nootropics, Functional Foods, and Dietary Patterns for Prevention of Cognitive Decline

Abstract Actual prevention of cognitive decline is probably the best strategy to address the rise in dementia expected in the coming decades, especially since therapeutic choices to revert or stop disease progression are lacking. Dietary approaches for preventing cognitive decline seem to be among the most promising options to slow age- and disease-related degeneration of the central nervous system. Several dietary patterns seem to be related to better cognitive performances late in life (the Mediterranean diet, dietary approaches to stop hypertension, and the Okinawan diet are good examples). The presence of vitamins, polyphenols, unsaturated fatty acids, and other bioactive compounds with neuroprotective effects is a core characteristic for functional foods useful for a healthy cognitive aging. Food- and spice-derived complements could be helpful before or alongside a pharmaceutical approach in cognitive decline, and medical foods composed of wide-spectrum bioactive compounds have the best chance of becoming an effective multilevel intervention.