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Biomedical subjects

M Fioravanti

Publications and source records attributed to M Fioravanti.

At least 19 recordsLinked to original sources
PubMed2005

Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly.

BACKGROUND: CDP-choline (cytidine 5'-diphosphocholine) is a precursor essential for the synthesis of phosphatidylcholine, one of the cell membrane components that is degraded during cerebral ischaemia to free fatty acids and free radicals. Animal studies suggest that CDP-choline may protect cell membranes by accelerating resynthesis of phospholipids. CDP-choline may also attenuate the progression of ischaemic cell damage by suppressing the release of free fatty acids. CDP-choline is the endogenous compound normally produced by the organism. When the same substance is introduced as a drug it can be called citicoline.CDP-choline is mainly used in the treatment of disorders of a cerebrovascular nature. The many years of its presence in the clinical field have caused an evolution in dosage, method of administration, and selection criteria of patients to whom the treatments were given. Modalities of the clinical studies, including length of observation, severity of disturbance, and methodology of evaluation of the results were also heterogeneous. In spite of uncertainties about its efficacy due to these complexities, CDP-choline is a frequently prescribed drug for cognitive impairment in several European countries, especially when the clinical picture is predominantly one of cerebrovascular disease, hence the need for this review. Due to its effects on the adrenergic and dopaminergic activity of the CNS, CDP-choline has also been used as an adjuvant in the treatment of Parkinson's disease. OBJECTIVES: To assess the efficacy of CDP-choline (cytidinediphosphocholine) in the treatment of cognitive, emotional, and behavioural deficits associated with chronic cerebral disorders in the elderly. SEARCH STRATEGY: The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 22 April 2004 using the terms CDP-choline, CDP, citicoline, cytidine diphosphate choline or diphosphocholine. The Register contains records from all major health-care databases and many ongoing trials databases and is updated regularly. SELECTION CRITERIA: All relevant unconfounded, double-blind, placebo-controlled, randomized trials of CDP-choline for cognitive impairment due to chronic cerebral disorders were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the included studies, extracted the data, and pooled it when appropriate and possible. The pooled odd ratios (95% Confidence Interval (CI)) or the average differences (95% CI) were estimated. No intention-to-treat data were available from the studies included. MAIN RESULTS: Fourteen studies were included in this review. Some of the included studies did not present numerical data suitable for analysis. Description of participants varied over the years and by type of disorders and severity, and ranged from aged individuals with subjective memory disorders to patients with Vascular Cognitive Impairment (mild to moderate), Vascular Dementia or Senile Dementia (mild to moderate). Seven of the included studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, four studies used periods extending over 2 and 3 months, one study observed continuous administration over 3 months and one study was prolonged, with 12 months of observation. The studies were heterogeneous in dose, modalities of administration, inclusion criteria for subjects, and outcome measures. Results were reported for the domains of attention, memory testing, behavioural rating scales, global clinical impression and tolerability. There was no evidence of a beneficial effect of CDP-choline on attention. There was evidence of benefit of CDP-choline on memory function and behaviour. The drug was well tolerated. AUTHORS' CONCLUSIONS: There was some evidence that CDP-choline has a positive effect on memory and behaviour in at least the short to medium term. The evidence of benefit from global impression was stronger, but is still limited by the duration of the studies. Further research with CDP-choline should focus on longer term studies in subjects who have been diagnosed with currently accepted standardised criteria, especially Vascular Mild Cognitive Impairment (VaMCI) or vascular dementia.

Aged↗
PubMed2004

Trazodone for agitation in dementia.

BACKGROUND: Behavioural and psychiatric disturbances affect at least 50% of people with Alzheimer's disease and other dementias. Neuroleptic drugs are extensively prescribed to treat behavioural manifestations of dementia in spite of only modest efficacy and a high frequency of adverse effects. There is clearly a need for safer and more effective remedies. Trazodone is a psychoactive compound with sedative and antidepressant properties, and with mixed serotonin agonist and antagonist effects. Functional serotonergic deficits may be related to the genesis of behavioural disturbances in dementia. OBJECTIVES: To determine the clinical efficacy and safety of trazodone, for any type of behavioural or psychological cognition in people with dementia without an additional diagnosis of depression. SEARCH STRATEGY: Trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 1 June 2004 using the terms trazodon*, beneficat, desirel, sideril, trazodil, trazalon. This register contains records from all major health care databases and many ongoing trials databases, and is updated regularly. SELECTION CRITERIA: All unconfounded, double-blind, randomised controlled trials, comparing trazodone with placebo in managing behavioural and psychiatric symptoms (except depression) in any type of dementia. DATA COLLECTION AND ANALYSIS: Available data for this analysis were extracted from the two included studies and odds ratios or average differences, with 95% confidence intervals, calculated. Intention-to-treat analysis was undertaken where possible. MAIN RESULTS: Two studies were included, comprising 104 participants with dementia. The trials differed in design - one being a parallel-group study of patients with Alzheimer's disease (Teri 2000) and one being a cross-over study of patients with frontotemporal dementia (Lebert 2004). It was not possible to pool the data. The studies were respectively of 16 and 6 weeks duration, using trazodone from 50 to 300mg daily. Both trials examined global clinical state, behavioural disturbances and cognitive function. Teri 2000 also assessed activities of daily living and caregiver burden. Compared with placebo, the use of trazodone was not associated with statistically significant benefits for behavioural manifestations as measured by various rating scales (ABID, CERAD-BRSD,CMAI, NPI). Analysis of changes from baseline for clinical impression of change and for cognitive function did not produce statistically significant results in favour of trazodone. A variety of adverse effects were recorded with no significant differences between trazodone and placebo. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend the use of trazodone as a treatment for behavioural and psychological manifestations of dementia. In order to assess effectiveness and safety of trazodone, longer-term trials are needed, involving larger samples of participants with a wider variety of types and severities of dementia.

Antidepressive Agents, Second-Generation↗
PubMed2004

Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly.

BACKGROUND: CDP-choline is used in the treatment of disorders of a cerebrovascular nature. The many years of its presence in the clinical field have caused an evolution in dosage, method of administration, and selection criteria of patients to which the treatments was given. Modalities of the clinical studies, including length of observation, severity of disturbance, and methodology of evaluation of the results were also heterogeneous. In spite of uncertainties about its efficacy due to these complexities, CDP-choline is a frequently prescribed drug for cognitive impairment in several European countries, especially when the clinical picture is predominantly one of cerebrovascular disease, hence the need for this review. OBJECTIVES: The objective is to assess the efficacy of CDP-choline (cytidinediphosphocholine) in the treatment of cognitive, emotional, and behavioural deficits associated with chronic cerebral disorders in the elderly. SEARCH STRATEGY: The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 20 January 2004 using the terms CDP-choline, CDP, citicolone, cytidine diphosphate choline or diphosphocholine. This register contains records from all major health care databases and many ongoing trials databases and is updated regularly. SELECTION CRITERIA: All relevant unconfounded, double-blind, placebo-controlled, randomized trials of CDP-choline for cognitive impairment due to chronic cerebral disorders are considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the included studies, extracted the data, and pooled it when appropriate and possible. The pooled odd ratios (95% CI) or the average differences (95% CI) were estimated. No intention-to-treat data were available from the studies included. MAIN RESULTS: Seven of the included studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, 4 studies used cycles extending over 2 and 3 months and one study observed continuous administration over 3 months. The studies were heterogeneous in dose, inclusion criteria for subjects, and outcome measures. Results are reported for the domains of attention, memory testing, behavioural rating scales, global clinical impression and tolerability. There is no significant evidence of a beneficial effect of CDP-choline on attention. There are significant beneficial effects of CDP-choline on memory function and behaviour. The drug is well tolerated. REVIEWERS' CONCLUSIONS: There is some evidence that CDP Choline has a positive effect on memory and behaviour in at least the short/medium term. The evidence of benefit from global impression is stronger, but is still limited by the duration of the studies. Further research with CDP-choline should focus on longer term studies in subjects who have been diagnosed with currently accepted standardised criteria, especially vascular dementia.

Aged↗
PubMed2004

Emotional activation of obese and normal women due to imagery and food content of verbal stimuli in a memory task.

The aim of this study is to look for correlation between a physiological variable (skin conductance, SCL) and cognitive variables (reaction time, RT and productivity score) obtained in a memory task. Subjects were 17 females, including 7 patients and 10 controls. Patients were recruited among women who went to a clinic for alimentary disorders because of obesity and volunteered for this study; controls were normal women of comparable age without any alimentary problem. Tonic variations of SCL were recorded by a computerized polygraph during the execution of the cognitive task, which consisted of a computerized presentation of frequent, everyday used words evenly divided according to an alimentary/nonalimentary content and to a high/low imagery quality. The acquisition session was followed by an immediate recognition session where subjects were asked to identify the previously presented words among an equal number of similar words not included in the acquisition list. The two session series (acquisition and recognition) were repeated three times to evaluate the learning curve and habituation. This same procedure was separately performed with high imagery alimentary/nonalimentary words and with another list of low imagery alimentary/nonalimentary words. During the recognition tasks, both RT and productivity scores were recorded. A correlation analysis between cognitive and physiological variables was carried out to explore how subjects with different attitudes to food react in cognitive and somatic terms when exposed to verbal stimuli concerning this topic and to neutral verbal stimuli. Results show that obese patients have a different emotional activation in front of these verbal stimuli where both the cognitive activity and the somatic responses are affected by their involvement with the verbal stimuli. On the contrary, the imagery effect does not seem to be influenced by the content and by the idiosyncratic reactions to it of the specific groups of subjects.

Adult↗
PubMed2002

Eating behavior of ballet dancers.

Ballet dancers are frequently regarded as having a higher risk of developing eating disorders (ED). This paper describes the eating habits and prevalence of ED in a group of female students from a dance academy in Rome, Italy. Participants were assessed with an array of measures conventionally employed (usually singly) in epidemiological studies of ED, namely: an anthropometrical-nutritional evaluation, the EAT, EDI, and BUT questionnaires, and the EDE interview. The 160 students who agreed to participate were evaluated anthropometrically, nutritionally and psychometrically and 83 underwent the EDE structured interview. Their calorie intake was insufficient in all age groups in terms of the nutritional standards required by their daily physical activity. EAT, EDI and BUT enhanced concerns about dieting, food intake control and body image. The significance of the correlations between calorie intake and the EAT Dieting and the EDI Perfectionism and Interceptive Awareness scores increased in function of age. Food, weight and body image concerns increased with age and length of time in the ballet environment The reduced calorie intake was not necessarily linked to the presence of psychopathological signs.

Adolescent↗
PubMed2002

Thyroid function in physiological aging and in centenarians: possible relationships with some nutritional markers.

Changes in thyroid function are often described in elderly subjects; however, their pathophysiologic significance and the possible contributory role of both malnutrition and nonthyroidal illness are still debated. The aim of this cross-sectional study was to investigate thyroid function in relationship to some markers of the nutritional status in a group of healthy old subjects and in some centenarians living in nursing homes. Patients included 24 clinically healthy elderly women (age, 71 to 93 years), 24 clinically healthy centenarian women (age, 100 to 106 years), and 20 healthy young subjects (age, 22 to 33 years). Blood samples were drawn from each subject for the evaluation of thyroid-stimulating hormone (TSH), free triiodothyronine (FT(3)), free thyroxine (FT(4),) reverseT(3) (rT3), autoantibodies against thyroglobulin (AbTg) and against thyroid peroxidase (AbTPO), and for the main humoral nutritional markers. TSH and thyroid hormones were assayed by fluoroimmunometric method; rT3 and thyroid autoantibodies by radioimmunoassay (RIA) and enzyme chemiluminescent immunometric assay, respectively. The mean values of TSH, FT(3) and FT(4) fell within the normal range in both groups. However, by comparison to old controls, in centenarian subjects, TSH levels were significantly lower, whereas rT(3) concentrations were slightly, but significantly, increased. Autoantibodies positivity was found in 4.16% of centenarians and in 10.4% and 13.6% of old and young controls. Thus, the incidence of thyroid autoantibodies was lower in centenarians than in old controls. Except for transferrin, lower than the normal range in centenarians, all of the other nutritional markers evaluated fell within the laboratory range of normality. Total cholesterol levels were significantly reduced in centenarians by comparison to old controls. Our results showed an age-related decline of the TSH levels and a significant increase of the rT(3) concentrations in centenarians by comparison to old controls. These findings may be related to an age-dependent reduction of the 5'-deiodinase activity rather than to important changes of nutritional markers.

Adult↗
PubMed2001

Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment.

BACKGROUND: Nicergoline is an ergot derivative currently in use in over fifty countries for more than three decades, for the treatment of cognitive, affective, and behavioral disorders of older people. It was initially considered as a vasoactive drug and mainly prescribed for cerebrovascular disorders. Recent findings suggest other actions which has provided a rationale for the use of nicergoline for the treatment of various forms of dementia, including Alzheimer's Disease. OBJECTIVES: To determine whether there is evidence of efficacy of nicergoline in the treatment of dementia and other age-associated forms of cognitive decline,and to assess the safety and tolerability of the drug. SEARCH STRATEGY: 1. Electronic databases search. The Cochrane Controlled Trials Register (which contains citations from the MEDLINE, EMBASE, Psych LIT, and hand searches of geriatric, dementia, psychogeriatric journals, and conference abstracts) was searched using the following terms: 'Nicergoline', 'Sermion'. 2. Reference search. The reference lists of all obtained studies was checked. 3. Pharmaceutical company Pharmacia & Upjohn, owners of the rights to produce and market nicergoline in various different countries, was asked to provide data and reports of clinical trials. In case of unavailability of numerical data in published studies, the authors of each paper, were asked for any published or unpublished data. SELECTION CRITERIA: - All unconfounded, double-blind, randomized, placebo-controlled, published and unpublished trials were sought. Non-randomized trials were excluded. Open trials were considered for inclusion if patients were randomized to the different treatment groups. - All patients diagnosed as having dementia or other cognitive disorder defined according to classification criteria accepted at the time of each study. - Nicergoline given at any dose for more than one day with placebo control. Type of outcome variables: 1. Cognitive function (as measured by psychometric tests). 2. Clinical impression (such as CIBIC or other clinical global measures of change). 3. Functional performance including dependency. 4. Behavioural disturbance. 5. Safety and acceptability as measured by the incidence of adverse effects (including side-effects) leading to withdrawal. 6. Death 7. Effect on carer 8. Use of services 9. Quality of life. DATA COLLECTION AND ANALYSIS: A comprehensive search of the international literature and the producing company archives has been performed to identify all possible sources of data for this review. Only those trials fulfilling the inclusion criteria of belonging to either category A or B of allocation concealment, as defined by the Cochrane Organisation, were examined for data extraction by one reviewer. If there was doubt then the other reviewer was consulted. Data availability restricted analyses to 'completers' analyses for the outcome measures. Outcomes able to be assessed included: Behaviour, Cognition, Clinical Judgment, Tolerability, EEG. MAIN RESULTS: The Sandoz Clinical Assessment Geriatric Scale (SCAG) was the outcome used in the largest number of patients (814 patients). The results from these studies were homogeneous in nature despite including patients observed for periods of time ranging from 2 months to 12 months. There was a difference in favour of the active treatment in reducing the behavioural symptoms described by this scale, -5.18 points [-8.03, -2.33]. This scale has a maximum of 133 points. The therapeutic effects of nicergoline seem to be evident by 2 months of treatment and maintained for 6 months. In general other behavioural outcome measures which include the GRS, the IADL, and the MACC and were episodically used in few studies, failed to demonstrate statistically significant results although there was a trend favouring treatment. Cognitive assessment has been performed in a moderate number of patients with the MMSE (261 patients) and the ADAS-Cog (342 patients). No significant heterogeneity was found for these trials, despite the trials extending over periods of treatment of 3 to 12 months. There was a difference between treatment and control groups on the MMSE favouring nicergoline treatment. At 12 months the effect size was 2.86 [0.98, 4.74] The effect size for the ADAS-Cog, used exclusively with Alzheimer's disease patients, did not reveal a significant benefit. At 12 months the trend favoured treatment (-1.64 [-4.62, 1.34]). The other results from various cognitive measures tended to favour nicergoline but this was based on a small number of cases. The clinical impression of change obtained from a total of 921 patients was homogeneous across the studies, despite reflecting changes over periods of time ranging from 2 to 12 months. The Peto odd ratio for improvement in the subjects treated with nicergoline over these varying time periods was 3.33 [2.50, 4.43]. Tolerability assessed in 1427 patients was homogeneous across all studies and demonstrated a mildly increased risk of adverse events on treatment, OR 1.51[1.10, 2.07]. REVIEWER'S CONCLUSIONS: The clinical studies on nicergoline were carried out with diverse criteria and modalities of evaluation. Despite this, the 14 studies included in this review, have presented generally consistent results. Results of this meta-analysis provide some evidence of positive effects of nicergoline on cognition and behaviour and these effects are supported by an effect on clinical global impression. There was some evidence that there were increased risk of adverse effects associated with nicergoline. These results were obtained on older patients with mild to moderate cognitive and behavioural impairment of various clinical origins, including chronic cerebrovascular disorders and Alzheimer's dementia. The few studies specifically performed on patients with Alzheimer's disease were performed with too few people to give a definitive answer to the questions concerning the use of nicergoline for this form of dementia. This drug has not been evaluated using current diagnostic categories such as MCI or in association with therapeutic agents of different nature such as cholinesterase or antioxidant drugs.

Cognition Disorders↗
PubMed2001

Memory rehabilitation in Alzheimer's disease: a review of progress.

BACKGROUND: Memory rehabilitation is a sadly misrepresented area of applied research in Alzheimer's disease. OBJECTIVES: To gather and evaluate recent evidence for the clinical effectiveness or ecologically validity of memory rehabilitation for mild to moderate Alzheimer's patients. METHODS: Computerised searches and some handsearching were conducted spanning the last five years, from 1995 to 2000, inclusively. Criteria for inclusion in this overview involved the use of a precise memory rehabilitation technique within an experimental study design applied to Alzheimer's patients with pre- and post-treatment evaluation. FINDINGS: Three potential levels of memory rehabilitation procedures with proven clinical or pragmatic efficacy were identified. The first level bears on the facilitation of residual explicit memory with structured support both at encoding and at subsequent recall; the second level of memory rehabilitation exploits the relatively intact implicit memory system (priming and procedural memory); the last deals with finding ways of coping with the patient's limited explicit memory capacities through the use of external memory aids. A proposal of suggestions for good practice and future research in memory rehabilitation is also offered with the hope to spur further development in this rapidly expanding area of applied research. CONCLUSION: The available evidence shows that alternative and innovative ways of memory rehabilitation for Alzheimer's patients can indeed be clinically effective or pragmatically useful with a great potential for use within the new culture of a more graded and proactive type of Alzheimer's disease care.

Adaptation, Psychological↗
PubMed2001

Age-related changes of the adrenal secretory pattern: possible role in pathological brain aging.

The biosynthetic dissociation of the adrenocortical secretion occurring with age may have a pathogenetic role in the pathophysiology of brain aging. We studied cortisol and DHEAS secretion in healthy old and young subjects, in senile dementia, in major depression of elderly subjects and in healthy centenarians. A clear age-related decline of DHEAS secretion was well evident in healthy centenarians, and a further decrease in DHEAS concentration was found in old depressed patients and moreover in the demented ones, by comparison with age-matched controls. The circadian profile of serum cortisol was clearly flattened in old subjects, due to the selective increase in the cortisol nocturnal levels, particularly evident in demented subjects; on the other hand, the morning serum cortisol levels were not significantly different among centenarians, young and old controls. The molar ratio between cortisol and DHEAS showed a significant age-related increase; the occurrence of senile dementia and of major depression played an additive role, by comparison to physiological aging. The qualitative and quantitative modifications of the adrenocortical secretion occurring with aging seem mainly dependent on age itself, but the occurrence of pathological conditions may amplify these changes. Since cortisol and DHEAS play opposite effects on the central nervous system, the evaluation of the ratio between cortisol and DHEAS seems to be a good marker of the neuroendocrine features in old subjects.

Adrenal Glands↗
PubMed2001

Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates.

The aim of this review was to examine the evidence for age-related changes of the hypothalamic-pituitary-adrenal (HPA) axis in both physiological and pathological aging, on the basis of the many data in the literature, as well as of our personal findings. A statistically significant circadian rhythmicity of serum cortisol was maintained in elderly subjects, even if with a reduced amplitude of the 24 h fluctuations and a trend to an increase of the serum levels in the evening and at night-time, in comparison with young controls. Furthermore, an age-related impairment of HPA sensitivity to steroid feedback was present in elderly people. The occurrence of senile dementia amplified the changes already present in physiological aging. While the cortisol secretion was generally well maintained in aging, the adrenal production of dehydroepiandrosterone and of its sulfate (DHEAS) exhibited an age-related decline. Therefore, the cortisol/DHEAS molar ratio was significantly higher in elderly subjects and even more in demented ones, than in young controls. Due to the opposite effects of cortisol and DHEAS on the brain and particularly on the hippocampal region, the imbalance between glucocorticoids and androgens occurring in physiological and even more in pathological aging, may have adverse effects on the function of this region, whose key role in learning and memory is well known.

Aging↗
PubMed2000

Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly.

BACKGROUND: The prevalent use of this compound in the treatment of disorders of a cerebrovascular nature does not mean that a homogeneous and consistent application of this therapy has been applied. Dosage, method of administration, and selection criteria of patients have varied. The modalities of the studies, including length of observation, severity of disturbance, and methodology of the evaluation of the results were also heterogeneous. In spite of uncertainties about its efficacy, CDP-choline is a frequently prescribed drug for cognitive impairment in several European countries, especially when the clinical picture is predominantly one of cerebrovascular disease, hence the need for this review. OBJECTIVES: The objective is to assess the efficacy of CDP-choline (cytidinediphosphocholine) in the treatment of cognitive, emotional, and behavioural deficits associated with chronic cerebral disorders of the elderly. SEARCH STRATEGY: The CDCIG register of trials was searched for all relevant, non-animal randomised controlled trials using the terms CDP-choline/CDP, Citicoline, Cytidine Diphosphate Choline and Diphosphocholine. The Psychlit (1974-1996), Psychiatry (1980-1996) and MEDLINE electronic databases have been searched independently by the reviewers. The reviewers have also contacted manufacturers of CDP-choline. SELECTION CRITERIA: All relevant, non-animal, unconfounded, double-blind, placebo-controlled, randomised trials of CDP-choline in cognitive impairment due to chronic cerebral disorders will be considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the included studies, extracted the data, and pooled it when appropriate and possible. The pooled odd ratios (95% CI) or the average differences (95% CI) were estimated. No intention-to-treat data were available from the studies included. MAIN RESULTS: Seven of the included studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, 2 studies used cycles extending over 2 and 3 months and one study observed continuous administration over 3 months. The studies were heterogeneous in dose, inclusion criteria for subjects, and outcome measures. Results are reported for the domains of attention, memory testing, behavioural rating scales, global clinical impression and tolerability. There was no significant evidence of a beneficial effect of CDP-choline on attention. There were modest, but significant, beneficial effects of CDP-choline on memory function and behaviour. For the outcome of clinical global impression, the odds ratio for improvement in the subjects treated with CDP-Choline as opposed to the subjects treated with placebo was 8.89 [5.19, 15.22]. The drug was well tolerated. REVIEWER'S CONCLUSIONS: There is some evidence that CDP Choline has a positive effect on memory and behaviour in at least the short term. The evidence of benefit from global impression is stronger, but is still limited by the duration of the studies. There is evidence that the effect of treatment is more homogeneous for patients with cognitive impairment secondary to cerebrovascular disorder. Other studies with a more appropriate length of treatment are recommended owing to the chronic and irreversible nature of the disorders for which this treatment is indicated.

Aged↗
PubMed2000

Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia.

The simultaneous evaluation of the circadian rhythm of plasma melatonin and ACTH and of serum cortisol and DHEAS represents a clinically reliable tool to appreciate the neuroendocrine changes occurring in physiological and pathological brain aging.A selective impairment of the nocturnal melatonin secretion has been observed in elderly subjects, being significantly related either to the age or to the severity of dementia. A significant increase of serum cortisol levels during evening- and night-times was found in elderly subjects, particularly if demented, when compared to young controls. Besides, both the circadian amplitude of cortisol rhythm and the nocturnal cortisol increase were significantly reduced in relation either to age or to cognitive impairment. By comparison to vascular dementia, patients with Alzheimer's disease exhibited the highest cortisol concentrations throughout the 24h. The sensitivity of the hypothalamic-pituitary-adrenal axis to the steroid feedback was significantly impaired in old subjects and particularly in the demented ones. The serum DHEAS levels were significantly lower in elderly subjects and even more in demented patients than in young controls. Consequently, a significant increase of the cortisol/DHEAS molar ratio was evident when going from young controls to healthy elderly subjects and to demented patients. In conclusion, the aging process affects many neuroendocrine functions resulting in subtle but clinically relevant consequences; the occurrence of senile dementia seems to play an additive role.

Adrenocorticotropic Hormone↗
PubMed2000

Overproduction of IFN-gamma and TNF-alpha from natural killer (NK) cells is associated with abnormal NK reactivity and cognitive derangement in Alzheimer's disease.

Alterations of natural killer (NK) function can be involved in the neuroimmune mechanism of neurodegeneration in dementia of the Alzheimer's type (DAT). NK cell cytotoxicity (NKCC) and the generation and release of IFN-gamma and TNF-alpha (spontaneous and modulated by IL-2) from pure NK cells (CD 16+, CD 56+, CD 3-) were studied together with circulating IFN-gamma and TNF-alpha levels and cognitive function in 22 old patients with DAT and 15 healthy old subjects. Higher (p < 0.001) IL-2 modulated NKCC (with IL-2 50 U/mL and 100 U/mL) was demonstrated in DAT patients (+35% and +99% from baseline) than in healthy subjects (+6% and +76% from baseline). Increased spontaneous and IL-2-induced release of IFN-gamma and TNF-alpha from NK cells were found in DAT patients compared to healthy subjects (p < 0.001), whereas no difference of serum IFN-gamma and TNF-alpha was demonstrated between DAT and control groups. Significant negative correlations among the spontaneous release of IFN-gamma and TNF-alpha from NK and the decrease of the score of cognitive function (MMSE) were found in patients with DAT. In conclusion, alterations of NKCC control and NK-derived cytokine release in DAT could be involved in the neuroinflammatory mechanism related to the progression of neurodegeneration and dementia.

Aged↗