Elena Mariani

Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease

In order to assess peripheral levels and activities of a broad spectrum of non-enzymatic and enzymatic antioxidants in elderly subjects with mild cognitive impairment (MCI) and Alzheimers disease (AD), plasma levels of water-soluble (Vitamin C and uric acid) and of lipophilic (Vitamin A, Vitamin E and carotenoids including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) antioxidant micronutrients as well as activities of plasma and red blood cell (RBC) superoxide dismutase (SOD) and of plasma glutathione peroxidase (GPx) were measured in 25 patients with MCI, 63 AD patients and 53 controls. Peripheral levels and activities of antioxidants were similarly lower in MCI and AD patients as compared to controls. As MCI may represent a prodromal stage of AD, and oxidative damage appears to occur as one of the earliest pathophysiological events in AD, an increased intake of antioxidants in patients with MCI could be helpful in lowering the risk of conversion to dementia.

Mild cognitive impairment: a systematic review.

MCI is a nosological entity proposed as an intermediate state between normal aging and dementia. The syndrome can be divided into two broad subtypes: amnestic MCI (aMCI) characterized by reduced memory, and non-amnestic MCI (naMCI) in which other cognitive functions rather than memory are mostly impaired. aMCI seems to represent an early stage of AD, while the outcomes of the naMCI subtypes appear more heterogeneous--including vascular dementia, frontotemporal dementia or dementia with Lewy bodies--but this aspect is still under debate. MCI in fact represents a condition with multiple sources of heterogeneity, including clinical presentation, etiology, and prognosis. To improve classification and prognosis, there is a need for more sensitive instruments specifically developed for MCI as well as for more reliable methods to determine its progression or improvement. Current clinical criteria for MCI should be updated to include restriction in complex ADL; also the diagnostic and prognostic role of behavioral symptoms and motor dysfunctions should be better defined. A multidisciplinary diagnostic approach including biological and neuroimaging techniques may probably represent the best option to predict the conversion from MCI to dementia. In this review we discuss the most recent aspects related to the epidemiological, clinical, neuropathological, neuroimaging, biochemical and therapeutic aspects of MCI, with specific attention to possible markers of conversion to dementia.

High Fruit and Vegetable Intake is Positively Correlated with Antioxidant Status and Cognitive Performance in Healthy Subjects

A higher daily intake of fruits and vegetables in healthy elderly is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables, but the impact on cognitive performance is unclear. Healthy community dwellers (45 to 102 years old, n=193) underwent cognitive testing and blood withdrawal for the measurement of antioxidant micronutrients and biomarkers of oxidative stress as well as administration of a food frequency questionnaire to assess the daily intake of fruits and vegetables (high intake HI, low intake LI). Ninety-four subjects of the HI group had significantly higher cognitive test scores, higher levels of carotenoids, alpha- and gamma-tocopherol as well as lower levels of F2 alpha isoprostanes than the 99 subjects of the LI group. Cognitive scores were directly correlated with blood levels of alpha-tocopherol and lycopene and negatively correlated with F2 alpha isoprostanes and protein carbonyls. The results were independent of age, gender, body mass index, education, total cholesterol, LDL- and HDL-cholesterol, triglycerides, and albumin. Healthy subjects of any age with a high daily intake of fruits and vegetables have higher antioxidant levels, lower levels of biomarkers of oxidative stress, and better cognitive performance than healthy subjects of any age consuming low amounts of fruits and vegetables. Modification of nutritional habits aimed at increasing intake of fruits and vegetables should be encouraged to lower prevalence of cognitive impairment in later life.

Conversion of MCI to dementia: Role of proton magnetic resonance spectroscopy

Mild cognitive impairment (MCI) represents a heterogeneous group of cognitive disturbances at high risk of dementia. The amnestic subtype (aMCI) might be a prodromal state of Alzheimers disease (AD). The aim of this study is the identification, by proton magnetic resonance spectroscopy (1H MRS), of modifications in brain metabolites able to detect subjects with aMCI at risk of conversion towards AD. Twenty-five subjects with aMCI and 29 normal elderly were enrolled; they underwent a comprehensive clinical and instrumental assessment, a cerebral 1H MRS scan to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI) and creatine (Cr) in the paratrigonal white matter, bilaterally. After 1 year, 5 MCI subjects became demented (progressive MCI, pMCI). Their baseline levels of metabolites were compared with those evaluated in stable MCI (sMCI) and in controls. We observed a significant difference of the NAA/Cr ratio between pMCI (1.48+/-0.08) and sMCI (1.65+/-0.12) and between pMCI and controls (1.63+/-0.16) in the left hemisphere, suggesting that this metabolic alteration can be detected before the clinical appearance of dementia.

Cognitive impairment is the major risk factor for development of geriatric syndromes during hospitalization: results from the GIFA study.

Objective: To detect the main factors associated with the occurrence of specific geriatric syndromes (namely pressure sores, fecal incontinence, urinary incontinence and falls) in elderly patients during hospitalization. Design: Observational prospective study. Setting: Eighty-one community and university hospitals throughout Italy. Participants: 13,729 patients aged 65 years and more, consecutively admitted to medical or geriatric acute wards during 20 months in the period between 1991 and 1998. Measurements: Occurrence of pressure sores, fecal incontinence, urinary incontinence and falls during the stay in hospital. Results: Pressure sores were already present in 3% of hospitalized subjects, fecal incontinence in 7.3%, while urinary incontinence, evaluated on a subgroup of total population (4,268 subjects), had a prevalence of 22.3%. During hospitalization (mean stay of 15 days), 74 subjects developed new pressure sores, 55 became fecal and 35 urinary incontinent, and 279 subjects had at least one episode of fall. In multivariate analyses, cognitive impairment, advanced age (85+ years), length of stay (more than 3 weeks) and severe disability were the main independent predictors of development of the four geriatric syndromes, with cognitive impairment as the most significant risk factor for all the four outcomes (OR 4.9, 95% CI 2.4–9.9 for pressure sores; OR 6.3, 95% CI 3.0–13.0 for fecal incontinence; OR 5.3, 95% CI 2.3–12.0 for urinary incontinence; OR 1.6, 95% CI 1.2–2.3 for falls). Conclusion: Very old people have a significant increased risk of several geriatric syndromes during the stay in hospital, particularly if it is long and they are cognitively impaired. A standardized comprehensive geriatric evaluation at admission could be helpful in detecting all subjects at risk and preventing the development of hospital-acquired geriatric syndromes.

Hallmarks of protein oxidative damage in neurodegenerative diseases: focus on Alzheimer’s disease

Summary.The pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, has been linked to a condition of oxidative and nitrosative stress, arising from the imbalance between increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and antioxidant defences or efficiency of repair or removal systems. The effects of free radicals are expressed by the accumulation of oxidative damage to biomolecules: nucleic acids, lipids and proteins. In this review we focused our attention on the large body of evidence of oxidative damage to protein in Alzheimer’s disease brain and peripheral cells as well as in their role in signalling pathways. The progress in the understanding of the molecular alterations underlying Alzheimer’s disease will be useful in developing successful preventive and therapeutic strategies, since available drugs can only temporarily stabilize the disease, but are not able to block the neurodegenerative process.

Neuropsychiatric symptoms in 921 elderly subjects with dementia: a comparison between vascular and neurodegenerative types.

Objective:  i) to describe the neuropsychiatric profile of elderly subjects with dementia by comparing vascular (VaD) and degenerative dementias, i.e. dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD); ii) to assess whether the severity and type of dementia are associated with clinically relevant neuropsychiatric symptoms (CR‐NPS).

Antioxidants for the treatment of mild cognitive impairment

Abstract The isolated deficit in recent memory frequently associated with decline to Alzheimers disease (AD) is defined as mild cognitive impairment (MCI). The observed progression of MCI to AD suggests a common pathogenesis between these two clinical syndromes, and several neuroimaging, neuropsychological and biological methods are applied with the purpose of identifying subjects at risk of AD. Among these methods, the evaluation of a condition of oxidative stress is gaining increasing attention. Since oxidative stress seems to be involved in the earliest phases of AD, and MCI may be considered as a prodromal phase of dementia, it is an attractive issue to focus therapeutic interventions on the early phase of the disease.

Elevated Lipid Peroxidation Biomarkers and Low Antioxidant Status in Atherosclerotic Patients with Increased Carotid or Iliofemoral Intima Media Thickness

Objectives Lipid peroxidation plays an important role in the development of atherosclerosis, a chronic, age-related disease process of the arterial wall with onset decades prior to its clinical manifestations. The aim of the study was to assess the association between the intima media thickness (IMT) of the major arteries as a clinical marker of atherosclerosis and markers of lipid peroxidation along with the antioxidant status in humans. Design Case-control study. Setting A university-affiliated outpatient clinic. Subjects Thirty patients (22 males, 8 females; 70.4 ± 7.3 years) with atherosclerosis of the carotid or iliofemoral arteries and 62 healthy controls (30 males, 32 females; 68.3 ± 4.3 years). Methods Plasma levels of 8,12-isoprostane F2α-VI (8,12-IPF2α-VI) were measured by gas chromatography/mass spectrometry, whereas levels of malondialdehyde (MDA), vitamins A (retinol) and E (α- and γ-tocopherol), and carotenoids were determined by high-performance liquid chromatography. The IMT was measured by B-mode ultrasonography. Results Patients showed, independent of fruit and vegetable intake, significantly lower plasma levels of retinol, α-tocopherol, and all carotenoids excluding β-cryptoxanthin compared with controls. On the contrary, plasma 8,12-IPF2α-VI levels were almost doubled (p < .001) and MDA levels increased by one-third (p < .01) in atherosclerotic patients compared with controls. Conclusions The analyses of isoprostanes and antioxidant nutrients in plasma as markers of oxidative stress and the parallel evaluation of IMT as a structural marker of atherosclerosis are suitable tools for investigating the role of antioxidants and oxidative stress in atherosclerosis.

Depression in the elderly: new concepts and therapeutic approaches

Depression is one of the leading causes of suffering in the elderly, but it is often under-diagnosed and under-treated, partly due to the false belief that depression is a common aspect of aging. Depression in the elderly is frequently comorbid with medical illnesses, may often be expressed by somatic complaints, and may be a risk factor for other diseases such as dementia and coronary artery disease. Depression decreases the quality of life and increases disability and the risk of mortality, also due to suicide. Although several effective antidepressant drugs are available, with a favorable therapeutic index, non-pharmacological treatments, such as psychotherapy and exercise, should receive greater attention, since combination therapy is probably more effective.