Relationship between proinflammatory cytokines (Il-1beta, Il-18) and leukocyte telomere length in mild cognitive impairment and Alzheimer's disease.

Inflammation plays a crucial role in Alzheimer's disease (AD). AD neurodegeneration and concurrent involvement of the peripheral immune system may promote leukocyte division and telomere shortening. We examined genotypes and plasma levels of two proinflammatory cytokines, IL-1beta and IL-18, and leukocyte telomere length (LTL) in patients with mild cognitive impairment (MCI) and AD. We wanted to determine whether changes in plasma IL-1beta and IL-18 levels, together with LTL shortening, could be diagnostic for disease progression from MCI to AD. Median plasma IL-1beta levels were in the order MCI patients (2.2 pg/ml) < AD patients (4.0 pg/ml), both of which differed significantly from the controls (0.0 pg/ml). In the AD patients, the lowest IL-1beta levels were associated with the presence of the C allele of IL-1beta rs16944 SNP. Median plasma IL-18 levels were in the order MCI patients (116.3 pg/ml) > AD patients (85.8 pg/ml), both of which were significantly higher than in the controls (17.6 pg/ml). Analysis of LTL showed a progressive reduction in the order controls > MCI > AD patients (p < 0.0001). Overall LTL reduction was correlated with increased plasma IL-1beta levels, substantiating the hypothesis that inflammatory processes secondary to neuroinflammation may trigger telomere attrition. Changes in plasma IL-1beta and Il-18 levels, and LTL seem to reflect shifts in AD stage; they may have potential use as blood biomarkers to monitor disease onset and progression from MCI to AD.

Common variants of human TERT and TERC genes and susceptibility to sporadic Alzheimers disease.

Studies investigating telomere length in association with cognitive decline, dementia, and sporadic Alzheimer's disease (AD) have frequently found shorter telomeres to be associated with the development of AD and telomerase expression with pathological processes in AD. Human telomerase is constituted by two components: the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). Genetic variation at the two loci has been investigated in relation to telomere length, longevity, and common diseases of advanced age, but not in relation to AD. We examined three polymorphisms of the TERT gene (VNTR MNS16A, rs2853691, rs33954691) and three polymorphisms of the TERC gene (rs12696304, rs3772190, rs16847897) in a sample of 220 AD patients and 146 controls. MNS16A LL genotype was found to be associated with an increased risk of AD only in males [interaction term adjusted OR=3.55 (95% CI 1.2-10.2)]. The three TERC single nucleotide polymorphisms are in strict linkage disequilibrium and their genotype combinations influenced the age at AD onset (AAO). The combined genotype GG-TT-CC was associated with a mean AAO six years lower (70.5±6.7) than that associated with the other genotype combinations (76.04±6.7, p=0.01). The fact that the MNS16 L allele has been reported to lower TERT expression, and that the TERC alleles G, T, C (rs12696304, rs3772190, rs16847897 in this order have been repeatedly found associated with shorter LTL, seems to corroborate the hypothesis of a role of telomere length and telomerase in AD susceptibility.

The Italian validation of the Anosognosia Questionnaire for Dementia in Alzheimer's disease.

Although the Anosognosia Questionnaire-Dementia (AQ-D) is one of the main instruments for assessing awareness in Alzheimer's disease (AD), the normative data were until now limited to people from Argentina and Japan. This study aims to validate this instrument in an European context, in particular in an Italian sample. In a multicenter project (Verona, Padova, and Trapani), 130 patients with AD and their caregivers participated in the study. Psychometric characteristics of AQ-D are confirmed indicating that the scale permits the early identification of anosognosia and the correct care management of patients. Indeed, anosognosia results to be present also in patients with very mild AD (moderate: 44.44%; mild: 47.17%; and very mild: 23.73%). Moreover, the results indicate that deficits in awareness may vary in severity and that different types of anosognosia may be identified.

Cognitive stimulation of executive functions in mild cognitive impairment: specific efficacy and impact in memory.

Executive functions play an important role in the maintenance of autonomy in day-to-day activities. Nevertheless, there is little research into specific cognitive training for Mild Cognitive Impairment (MCI). We present the results of a program which aims to teach specific strategies and metacognitive abilities in order for patients to be able to carry out attentional and executive tasks. Two groups (A and B) were compared in a cross-over design. After the first evaluation, Group A (but not B) participated in a six month cognitive stimulation program. After a second assessment, only Group B received treatment and then a final evaluation was carried out on both groups. The results show that: i) both groups improved their performance as an effect of training; ii) improvements generalized to memory and general cognitive tasks; iii) in the interval without training, Group B's performance worsened and iv) Group A partially maintained their results over time.

Awareness of cognitive deficits and clinical competence in mild to moderate Alzheimer's disease: their relevance in clinical practice.

Awareness of cognitive deficits and clinical competence were investigated in 79 mild to moderate Alzheimer's disease patients. Awareness was assessed by the anosognosia questionnaire for dementia, and clinical competence by specific neuropsychological tests such as trail making test-A, Babcock story recall test, semantic and phonemic verbal fluency. The findings show that 66 % of the patients were aware of memory deficits, while the 34 % were unaware. Deficit in awareness correlated with lower scores on the Mini Mental State Examination test that, in the score range from 24.51 to 30 and from 19.50 to 24.50, appeared to be a significant predictor of level of awareness. None of the AD patients had fully preserved clinical competence, only 7 patients (9 %) had partially preserved clinical competence and 72 patients (91 %) had completely lost clinical competence. All the patients with partially preserved clinical competence (9 %) were aware of their memory deficit. The study indicates that neuropsychological tests used for the assessment of executive functions are not suitable for investigating clinical competence. Therefore, additional and specific tools for the evaluation of clinical competence are necessary. Indeed, these might allow clinicians to identify AD patients who, despite their deficits in selected functions, retain their autonomy of choice as well as recognize those patients who should proceed to the nomination of a legal representative.

Energy balance in Alzheimer's disease.

Alzheimer s disease is the most frequent cause of dementia in elderly people and it is one of the leading causes of death among older individuals. Weight loss is a frequent clinical finding in Alzheimer s disease patients, and it is actually listed as a symptom consistent with the diagnosis of Alzheimer s disease, but its significance has not been clearly understood until now. This review examines the role of the components of energy balance in determining weight loss in AD patients, on the basis of data collected from the literature. We also considered the possible causes of anorexia in AD patients. In the last years many researchers investigated the possible role of abnormally high energy expenditure, or low energy intakes, or both, to explain weight loss in these patients. Studies on energy intake, energy expenditure and body composition in AD patients have been reviewed. The results of published studies do not seem to support the hypothesis of an hypermetabolic state or inadequate energy intake in AD patients, but further studies, with greater samples are necessary in the future to investigate weight loss in AD patients. A better understanding of this finding could be important to obtain the maximal lifespan of demented patients.

[Taste impairment in Alzheimer's disease]. / Etude du goût dans la maladie d'Alzheimer.

We conducted a study of Alzheimer's disease focusing on taste impairment to determine at which step of gustatory information processing (discriminative or perceptive, gnosic or associative, gustatory-verbal) possible perturbations might be located. We used various foods found in a normal diet. Twenty patients and a matched control group participated in this study. The patients were divided into two subgroups according to disease severity (mild, moderate or severe). The study showed that patients with Alzheimer's disease exhibited an impairment at all three levels of gustatory information processing. Impairment of discriminative and gustatory-verbal stages was more obvious in the group of patients with severe Alzheimer's disease. Our study also showed that the gustatory deficiency can be described as an associative agnosia in the mild stage of Alzheimer's disease. This concept is in line with the notion of a dissociation between preservation of olfactory and gustatory thresholds and an alteration in odor identification in patients with mild stage Alzheimer's disease, suggesting that the alteration is central rather than peripheral. Our findings suggest that an alteration of the associative level of gustatory information processing can be found in Alzheimer's disease early stage.