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Objective: To investigate the possible role of diet in age-related cognitive decline (ARCD) and cognitive impairment of both degenerative (Alzheimer's disease, AD) and vascular (vascular dementia, VaD) origin.Design: Literature review.Results: In an elderly population of southern Italy with a typical Mediterranean diet, high energy intake of monounsaturated fatty acids (MUFA) appeared to be associated with a high level of protection against ARCD. In addition, dietary fat and energy in the elderly seem to be risk factors, while fish consumption and cereals are found to reduce the prevalence of AD in European and North American countries. Finally, the relative risk of dementia (AD and VaD) was lower in the subjects of a French cohort who drank three or four glasses of red wine each day compared with total abstainers.Conclusion: Essential components of the Mediterranean diet--MUFA, cereals and wine--seem to be protective against cognitive decline. As such, dietary antioxidants and supplements, specific macronutrients of the Mediterranean diet, oestrogens and anti-inflammatory drugs may act synergistically with other protective factors, opening up new therapeutic interventions for cognitive decline. [ABSTRACT FROM AUTHOR]

A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer's disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD. [ABSTRACT FROM AUTHOR]

Background. Depression is recognized as being associated with increased mortality. However, there has been little previous research on the impact of longitudinal changes in late-life depressive symptoms on mortality, and of their remission in particular. Method. As part of a prospective, population-based study on a random sample of 5632 subjects aged 65-84 years, with a 10-year follow-up of vital status, depressive symptoms were assessed by the 30-item Italian version of the Geriatric Depression Scale (GDS). The number of participants in the GDS measurements was 3214 at baseline and 2070 at the second survey, 3 years later. Longitudinal changes in depressive symptoms (stable, remitted, worsened) were examined in participants in both evaluations (n = 1941). Mortality hazard ratios (MHRs) according to severity of symptoms and their changes over time were obtained by means of Cox proportional hazards regression models, adjusting for age and other potentially confounding factors. Results. Severity is significantly associated with excess mortality in both genders. Compared to the stability of depressive symptoms, a worsened condition shows a higher 7-year mortality risk [MHR 1.46, 95% confidence interval (CI) 1.15-1.84], whereas remission reduces by about 40% the risk of mortality in both genders (women MHR 0.55, 95% CI 0.32-0.95; men MHR 0.59, 95% CI 0.37-0.93). Neither sociodemographic nor medical confounders significantly modified these associations. Conclusions. Consistent with previous reports, the severity and persistence of depression are associated with higher mortality risks. Our findings extend the magnitude of the association demonstrating that remission of symptoms is related to a significant reduction in mortality, highlighting the need to enhance case-finding and successful treatment of late-life depression. [ABSTRACT FROM AUTHOR]

Dementia is an increasingly common disease in the aging population, and the numbers are expected to rise exponentially in coming years. Therefore, there is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Despite a substantial increase in the epidemiological and clinical evidence on frailty, there is no consensus on its definition or on what criteria should be used to identify older individuals with frailty. Frailty appears to be a nonspecific state of vulnerability, which reflects multisystem physiological change. In fact, current thinking is that not only physical but also psychological, cognitive and social factors contribute to this multidimensional syndrome and need to be taken into account in its definition and treatment. Cognition has already been considered as a component of frailty, and it has been demonstrated that it is associated with adverse health outcomes. In a recent population-based study, physical frail demented patients were at higher risk of all-cause mortality over 3- and 7-year follow-up periods. Several studies have also reported that physical frailty is associated with low cognitive performance, incidence of Alzheimer's disease (AD), and mild cognitive impairment, and AD pathology in older persons with and without dementia. Most frailty instruments use a dichotomous scoring system classifying a person as either frail or not frail, while a continuous or an ordinal scoring system on multiple levels would be preferable to be used as an outcome measure. Recently, a Multidimensional Prognostic Index (MPI), derived from a standardized comprehensive geriatric assessment, was effective in predicting short- and long-term mortality risk in hospitalized patients with dementia. Overall taken together these findings supported the concept that outcome measures linked to multidimensional impairment may be extremely important in making clinical decisions, especially for monitoring drug treatment in randomized clinical trials also for predementia and dementia syndromes. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI) is recognized as a prodromal phase of dementing disorders, and it has been suggested that oxidative stress may play a role in the pathogenesis of Alzheimer's disease (AD), and in predicting progression of MCI to AD. In the present article, on the basis of an increasing body of evidence from cross-sectional and longitudinal studies, we discussed the issue of the possible impact of antioxidant compounds from diet and supplementation on MCI and its progression to AD. [ABSTRACT FROM AUTHOR]

Objective: The authors investigated the relationship of metabolic syndrome (MetS) and its individual components with incident dementia in a prospective population-based study with a 3.5-year follow-up.Methods: A total of 2097 participants from a sample of 5632 subjects (65-84 years old) from the Italian Longitudinal Study on Ageing were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. Dementia, Alzheimer disease (AD) and vascular dementia (VaD) were classified using current published criteria.Results: MetS subjects (N=918) compared with those without MetS (N=1179) had an increased risk for VaD (1.63% vs 0.85%, adjusted hazard ratio (HR) 3.71, 95% CI 1.40 to 9.83). After excluding 338 subjects with baseline undernutrition, MetS subjects compared with those without MetS had an elevated risk of VaD (adjusted HR, 3.82; 95% CI 1.32 to 11.06). Moreover, those with MetS and high inflammation had a still further higher risk of VaD (multivariate adjusted HR, 9.55; 95% CI 1.17 to 78.17) compared with those without MetS and high inflammation. On the other hand, those with MetS and low inflammation compared with those without MetS and low inflammation did not exhibit a significant increased risk of VaD (adjusted HR, 3.31, 95% CI 0.91 to 12.14). Finally, a synergistic MetS effect versus its individual component effects was verified on the risk of VaD.Conclusion: In our population, MetS subjects had an elevated risk of VaD that increased after excluding patients with baseline undernutrition and selecting MetS subjects with high inflammation. [ABSTRACT FROM AUTHOR]

Drugs currently used to treat Alzheimer's Disease (AD) have limited therapeutic value and do not affect the main neuropathological hallmarks of the disease, i.e., senile plaques and neurofibrillar tangles. Senile plaques are mainly formed of beta-amyloid (Abeta), a 42-aminoacid peptide. Neurofibrillar tangles are composed of paired helical filaments of hyperphosphorylated tau protein. New, potentially disease-modifying, therapeutic approaches are targeting Abeta and tau protein. Drugs directed against Abeta include active and passive immunization, that have been found to accelerate Abeta clearance from the brain. The most developmentally advanced monoclonal antibody directly targeting Abeta is bapineuzumab, now being studied in a large Phase III clinical trial. Compounds that interfere with proteases regulating Abeta formation from amyloid precursor protein (APP) are also actively pursued. The discovery of inhibitors of beta-secretase, the enzyme that regulates the first step of the amyloidogenic metabolism of APP, has been revealed to be particularly difficult due to inherent medicinal chemistry problems, and only one compound (CTS-21166) has reached clinical testing. Conversely, several compounds that inhibit gamma-secretase, the pivotal enzyme that generates Abeta, have been identified, the most advanced being LY-450139 (semagacestat), now in Phase III clinical development. Compounds that stimulate alpha-secretase, the enzyme responsible for the non-amyloidogenic metabolism of APP, are also being developed, and one of them, EHT-0202, has recently entered Phase II testing. Potent inhibitors of Abeta aggregation have also been identified, and one of such compounds, PBT-2, has provided encouraging neuropsychological results in a recently completed Phase II study. Therapeutic approaches directed against tau protein include inhibitors of glycogen synthase kinase- 3 (GSK-3), the enzyme responsible for tau phosphorylation and tau protein aggregation inhibitors. NP-12, a promising GSK-3 inhibitor, is being tested in a Phase II study, and methylthioninium chloride, a tau protein aggregation inhibitor, has given initial encouraging results in a 50-week study. With all these approaches on their way, the hope for disease-modifying therapy in this devastating disease may become a reality in the next 5 years. [ABSTRACT FROM AUTHOR]

In the last decade, advances in understanding the neurobiology of Alzheimer's disease (AD) have translated into an increase in clinical trials assessing various potential AD treatments. At present, drugs used for the treatment of AD only slightly delay the inevitable symptomatic progression of the disease and do not affect the main neuropathological hallmarks of the disease, i.e. senile plaques and neurofibrillary tangles. Brain accumulation of oligomeric species of beta-amyloid (A beta) peptides, the principal components of senile plaques, is believed to play a crucial role in the development of AD. Based on this hypothesis, huge efforts are being made to identify drugs able to interfere with proteases regulating A beta formation from amyloid precursor protein (APP). Compounds that stimulate alpha-secretase, the enzyme responsible for non-amyloidogenic metabolism of APP, are being developed and one of these, EHT-0202, has recently commenced evaluation in a phase II study. The discovery of inhibitors of beta-secretase (memapsin-2, beta-amyloid cleaving enzyme-1 [BACE-1]), the enzyme that regulates the first step of amyloidogenic APP metabolism, has proved to be particularly difficult because of inherent medicinal chemistry issues and only one compound (CTS-21166) has proceeded to clinical testing. Conversely, several compounds that inhibit gamma-secretase, the pivotal enzyme that generates A beta, have been identified, the most advanced being LY-450139 (semagacestat), presently in phase III clinical development. There has been considerable disappointment over the failure of a phase III study of tarenflurbil, a compound believed to modulate the activity of gamma-secretase, after encouraging phase II findings. Nevertheless, other promising gamma-secretase modulators are being developed and are approaching clinical testing. All these therapeutic approaches increase the hope of slowing the rate of decline in patients with AD and modifying the natural history of this devastating disease within the next 5 years. [ABSTRACT FROM AUTHOR]

BACKGROUND: Subacromial impingement syndrome (SAIS) is a painful condition resulting from the entrapment of anatomical structures between the anteroinferior corner of the acromion and the greater tuberosity of the humerus. OBJECTIVE: The aim of this study was to evaluate the short-term effectiveness of high-intensity laser therapy (HILT) versus ultrasound (US) therapy in the treatment of SAIS. DESIGN: The study was designed as a randomized clinical trial. SETTING: The study was conducted in a university hospital. PATIENTS: Seventy patients with SAIS were randomly assigned to a HILT group or a US therapy group. INTERVENTION: Study participants received 10 treatment sessions of HILT or US therapy over a period of 2 consecutive weeks. MEASUREMENTS: Outcome measures were the Constant-Murley Scale (CMS), a visual analog scale (VAS), and the Simple Shoulder Test (SST). RESULTS: For the 70 study participants (42 women and 28 men; mean [SD] age=54.1 years [9.0]; mean [SD] VAS score at baseline=6.4 [1.7]), there were no between-group differences at baseline in VAS, CMS, and SST scores. At the end of the 2-week intervention, participants in the HILT group showed a significantly greater decrease in pain than participants in the US therapy group. Statistically significant differences in change in pain, articular movement, functionality, and muscle strength (force-generating capacity) (VAS, CMS, and SST scores) were observed after 10 treatment sessions from the baseline for participants in the HILT group compared with participants in the US therapy group. In particular, only the difference in change of VAS score between groups (1.65 points) surpassed the accepted minimal clinically important difference for this tool. LIMITATIONS: This study was limited by sample size, lack of a control or placebo group, and follow-up period. CONCLUSIONS: Participants diagnosed with SAIS showed greater reduction in pain and improvement in articular movement functionality and muscle strength of the affected shoulder after 10 treatment sessions of HILT than did participants receiving US therapy over a period of 2 consecutive weeks. [ABSTRACT FROM AUTHOR]

Background. Subacromial impingement syndrome (SAIS) is a painful condition resulting from the entrapment of anatomical structures between the anteroinferior corner of the acromion and the greater tuberosity of the humerus. Objective. The aim of this study was to evaluate the short-term effectiveness of high-intensity laser therapy (HILT) versus ultrasound (LIS) therapy in the treatment of SAIS. Design. The study was designed as a randomized clinical trial. Setting. The study was conducted in a university hospital. Patients. Seventy patients with SAIS were randomly assigned to a HILT group or a US therapy group. Intervention. Study participants received 10 treatment sessions of HILT or US therapy over a period of 2 consecutive weeks. Measurements. Outcome measures were the Constant-Murley Scale (CMS), a visual analog scale (VAS), and the Simple Shoulder Test (SST). Results. For the 70 study participants (42 women and 28 men; mean [SD] age = 54.1 years [9.0]; mean [SD] VAS score at baseline=6.4 [1.7]), there were no between-group differences at baseline in VAS, CMS, and SST scores. At the end of the 2-week intervention, participants in the HILT group showed a significantly greater decrease in pain than participants in the US therapy group. Statistically significant differences in change in pain, articular movement, functionality, and muscle strength (force-generating capacity) (VAS, CMS, and SST scores) were observed after 10 treatment sessions from the baseline for participants in the HILT group compared with participants in the US therapy group. In particular, only the difference in change of VAS score between groups ( 1.65 points) surpassed the accepted minimal clinically important difference for this tool. Limitations. This study was limited by sample size, lack of a control or placebo group, and follow-up period. Conclusions. Participants diagnosed with SAIS showed greater reduction in pain and improvement in articular movement functionality and muscle strength of the affected shoulder after 10 treatment sessions of HILT than did participants receiving US therapy over a period of 2 consecutive weeks. [ABSTRACT FROM AUTHOR]

Since the therapeutic options currently available have demonstrated limited efficacy, the search for preventive strategies for cognitive decline and dementia is mandatory. A possible role of vascular and lifestyle-related factors was recently proposed for age-related changes of cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer’s disease, AD) or vascular origin. At present, cumulative evidence suggested that vascular risk factors may be important in the development of mild cognitive impairment (MCI), dementia, and AD. Among vascular-related factors, metabolic syndrome has been associated with the risk of cognitive decline and overall dementia. Moderate alcohol drinking has been proposed as a protective factor against MCI and dementia in several longitudinal studies, but contrasting findings also exist. However, in most cases, these were only observational studies, and results are awaited from large multicenter randomized clinical trials in older persons. At present, vascular risk factor management, lifestyle changes, and drugs could be employed together to delay the onset of dementia syndromes. [ABSTRACT FROM AUTHOR]

Currently available epidemiological evidence suggested that an increase of saturated fatty acids (SFA) could have negative effects on cognitive functions, while increased polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) may be protective against cognitive decline. In a Southern Italian elderly population from the Italian Longitudinal Study on Aging (ILSA), a clear reduction of risk of age-related cognitive decline (ARCD) has been found with elevated intake of PUFA and MUFA. Furthermore, in the ELSA, while dietary fatty acids intakes were not associated with incident mild cognitive impairment (MCI), high PUFA intake appeared to have borderline non-significant trend for a protective effect against the development of MCI. These epidemiological findings on predementia syndromes, i.e. MCI or ARCD, together with a recent randomised controlled trial on a possible effect on cognitive and depressive symptoms of -3 PUFA supplementation in patients with very mild AD, suggested a possible role of fatty acids intake in maintaining adequate cognitive functioning and possibly in preventing or delaying the onset of dementia. [ABSTRACT FROM AUTHOR]

Reelin, a serine protease encoded by the RELN gene, is part of the apolipoprotein E (apoE) biochemical pathway that is involved in the pathogenesis of Alzheimer's disease (AD). Sex-related differences in the epidemiology, pathology and clinical characteristics of AD have been reported. To explore the potential contribution of RELN gene variants in the pathogenesis of AD, we investigated three polymorphisms spanning the RELN locus, i.e., a triplet tandem repeat in the 5'UTR and two single-nucleotide polymorphisms (SNPs) rs607755 and rs2229874, located in the splice-junction of exon 6 and in the coding region of exon 50. The analysis was made in 223 sporadic AD patients and 181 age-matched controls of Caucasian ethnicity. Significant differences between AD patients and controls were found in distribution of 5'UTR and rs607755 genotypes, whereas no differences were found in the distribution of rs2229874 genotypes. When patients and controls were divided according to sex, significant differences in genotype distribution were found in females and not in males, also after adjustment for APOE genotypes. These findings suggest that RELN gene variants may play a role in the pathogenesis of AD, particularly in females. [ABSTRACT FROM AUTHOR]

AIMS: We evaluated the impact of depressive symptoms on the rate of incident mild cognitive impairment (MCI) after a 3.5-year follow-up, and we assessed the interaction between depressive symptoms and vascular risk factors for incident MCI. METHODS: A total of 2,963 individuals from a sample of 5,632 65- to 84-year-old subjects were cognitively and functionally evaluated at the 1st and 2nd surveys of the Italian Longitudinal Study on Aging, a prospective cohort study with a 3.5-year follow-up. MCI and dementia were classified using current clinical criteria. Depressive symptoms were measured with the Geriatric Depression Scale. RESULTS: Among the 2,963 participants, 139 prevalent MCI cases were diagnosed at the 1st survey. During the 3.5-year follow-up, 105 new events of MCI were diagnosed. We did not observe any significant association between depressive symptoms and incident MCI (RR = 1.25, 95% CI = 0.85-1.84, chi(2) = 1.30, p < 0.25). No sociodemographic variables or vascular risk factors modified the relationship between depressive symptoms and incident MCI. CONCLUSION: In our population, depressive symptoms were not associated with the rate of incident MCI. Our findings did not support a role of sociodemographic variables or vascular risk factors in the link between depressive symptoms and incident MCI. [ABSTRACT FROM AUTHOR]

BACKGROUND: The glutamatergic neurotransmitter systems play a crucial role in memory formation and information processing. Alterations in this system contribute to the manifestation of symptoms in Alzheimer's disease (AD). Glutamate transmits signals via the N-methyl-D-aspartate receptors (NMDARs). Aims: The potential involvement of polymorphisms in the GRIN2B gene, encoding subunit 2B of the NMDA receptor, in the risk for AD was evaluated. METHODS: We investigated the 3 single-nucleotide polymorphisms (SNPs) rs1019385, rs1806201 and rs890, i.e. the G(-200)-->T transversion in the 5'UTR, the A(2664)-->G transition in exon 13 and the G(5072)-->T transition in the 3'UTR of the GRIN2B gene, in 222 Caucasian AD patients and 170 healthy Caucasian age-matched controls. RESULTS: No differences were found in the overall distribution of the single-nucleotide polymorphism genotypes between AD patients and healthy controls, even when the analysis was adjusted for sex, age and APOE. As expected from genotype frequencies, no differences were found in the distribution of the estimated allele and haplotype frequencies between AD patients and healthy controls. CONCLUSION: In this study no significant association between polymorphisms in the GRIN2B gene and AD was observed. Further investigations of polymorphisms in the gene encoding the NMDA receptor 2B subunit in AD patients with different genetic setting are needed to clarify their role in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Recent population-based studies identified the magnitude of interleukin 6 (IL6) serum levels as a marker for functional disability, and a predictor of disability and mortality among the elderly. We investigated whether there was evidence in Southern Italy of an association between the IL6 gene variable number of tandem repeats (VNTR) polymorphism and extreme longevity, and tested for the possible interaction of apolipoprotein E ( APOE) alleles with the IL6 VNTR alleles. Four alleles coding for variants of four different lengths have been identified: allele A [760 base pairs (bp)], allele B (680 bp), allele C (640 bp), and allele D (610 bp). IL6 VNTR and APOE allele and genotype frequencies were studied in a total of 61 centenarians and 94 middle-aged subjects from Southern Italy. The IL6 VNTR allele B was overrepresented in the younger control group compared with centenarians (odds ratio: 0.56, 95% confidence interval: 0.35–0.88, Bonferroni p-value < 0.05). No interactions between IL6 VNTR alleles and APOE alleles on the odds ratios to reach extreme longevity were evaluated for the smallest number of subjects in centenarians and younger controls. Our findings suggested that the presence of the IL6 VNTR allele B could be detrimental for reaching extreme longevity. [ABSTRACT FROM AUTHOR]

The human apoE gene ( APOE, GenBank accession AF261279) shows a common polymorphism, with the three ℇ2, ℇ3 and ℇ4 alleles resulting from the haplotypes of two C→T SNPs. However, whereas the three common T-T, T-C and C-C haplotypes corresponding to the ℇ2, ℇ3 and ℇ4 alleles are well known, the last C-T haplotype (GenBank accession AY077451), encoding a fourth apoE allele, has rarely been reported. We detected this fourth allele in a Caucasian patient with motor neuron disease (MND). According to the literature we refer to this allele as ℇ3r. Although several explanations may be proposed for its formation, the existence of this fourth allele is consistent with the evolutionary hypothesis generally accepted for the apoE alleles. The rarity and physiological role of ℇ3r remains to be explained, and requires further investigation. [ABSTRACT FROM AUTHOR]

Aims: We estimated the prevalence and incidence rates of depressive symptoms and the role of vascular risk factors and sociodemographic variables on the occurrence of depressive symptoms in mild cognitive impairment (MCI). Methods: In the Italian Longitudinal Study on Aging, 2,963 individuals from 5,632 65- to 84-year-old subjects were evaluated at the 1st and 2nd survey, with a 3.5-year follow-up. Dementia and MCI were classified using current criteria. Depressive symptoms were measured with the Geriatric Depression Scale. Results: Among the 2,963 participants, 139 prevalent MCI cases were diagnosed with a depressive symptoms prevalence rate of 63.3%. During the 3.5-year follow-up, we estimated an incidence rate of depressive symptoms of 29.6 per 100 person-years. No sociodemographic variables or vascular risk factors modified the incidence of depressive symptoms in cognitively stable MCI patients or in MCI patients who reverted to normal cognition. Conclusion: In our population, there was a high prevalence and incidence of depressive symptoms in MCI. Our findings do not provide support for a possible role of vascular risk factors in the development of depressive symptoms in MCI, although these findings were based on relatively few cases of MCI, limiting the capacity to draw definitive conclusions. Copyright (c) 2007 S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]

We investigated the association of sex and age with the occurrence of apolipoprotein E (apoE) and angiotensin-converting enzyme (ACE) genotypes in healthy aging and longevity in 1344 healthy individuals and 64 centenarians. As compared to participants younger than 60 years, a significant higher frequency of the apoE/epsilon2 was observed in men aged 60-90 years (p <.001) and in centenarians (p <.001). Logistic regression analysis confirmed this outcome in both participants aged 60-90 years (odds ratio [OR] = 1.897; 95% confidence interval [CI], 1.227-2.931) and centenarians (OR = 3.263; 95% CI, 1.860-5.722). A further significant association of ACE/D allele and age was observed in centenarians (OR = 2.135; 95% CI, 1.253-3.636). Heterosis was also observed at the ACE locus. No relationship between apoE and ACE polymorphism was found. These findings suggest a role of sex in the association of apoE and ACE gene polymorphisms with healthy aging and longevity. [ABSTRACT FROM AUTHOR]

Summary. In recent years, it is becoming apparent that genes may play an important role in the development of late-onset Alzheimer’s disease (LOAD), and genetic studies could unravel new clues. Based on a growing vascular hypothesis for the pathogenesis of LOAD and other dementias, there is increasing interest for environmental and genetic vascular factors. Polymorphisms in different susceptibility genes already implicated in vascular disease risk are now also being suggested as possible genetic markers for increased risk of developing LOAD; however, many of these studies have shown conflicting results. Thus far, the apolipoprotein E (APOE) gene seems to be the only vascular susceptibility factor that is agreed to play a role in the multifactorial pathogenesis of AD although emerging genetic and biological evidence is now strengthening the case for additional inclusion of angiotensin I-converting enzyme 1 (ACE1) into this category. This review will focus on the current knowledge on genetic and nongenetic vascular factors likely to be involved in LOAD, with special emphasis placed on the APOE and ACE1 genes. [ABSTRACT FROM AUTHOR]

Summary. Recent findings suggest a possible role of diet in age-related cognitive decline, and cognitive impairment of both degenerative (Alzheimer's disease, AD) or vascular origin. In particular, in an older population of Southern Italy with a typical Mediterranean diet, high monounsaturated fatty acids energy intake appeared to be associated with a high protection against cognitive decline. In addition, dietary fat and energy in older people seem to be risk factors, while fish consumption and cereals are found to reduce the prevalence of AD in the European and North American countries. Moreover, foods with large amounts of aluminium-containing additives or aluminium from drinking water may affect the risk of developing AD. Vitamin deficiencies, especially vitamin B6, B12 and folates, and antioxidant deficiencies (vitamins E and C) could also influence the memory capabilities and have an effect on cognitive decline. Dietary anti-oxidants and supplements and specific macronutrients of the diet may act synergistically with other protective factors opening new possibilities of intervention for cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives: To explore the possible role of serum lipoprotein(a) (Lp(a)), apolipoprotein E polymorphism, and total cholesterol (TC) serum concentrations in Alzheimer's disease (AD).Methods: Lp(a) serum concentrations, apolipoprotein E genotypes, and TC serum concentrations were determined in 61 patients with a diagnosis of probable AD and in 63 healthy unrelated age matched controls. Genomic DNA was obtained and amplified by polymerase chain reaction and apolipoprotein E genotypes were defined following a previously described procedure.Results: Lp(a) serum concentrations were significantly associated in a non-linear relation with an increased risk for AD, independently of apolipoprotein E genotypes and sex and dependent on age (truth association) and TC serum concentrations (spurious association). The effect of age adjusted for TC on the odds of having AD increased non-linearly with increasing Lp(a) serum concentrations, with a plateau between 70 and 355 mg/l (odds ratio 11.33). For Lp(a) serum concentrations > or = 360 mg/l, the effect of age (> or = 72 years) was associated with a reduction in odds of having AD (odds ratio 0.15).Conclusion: It is suggested that increased Lp(a) serum concentrations, by increasing the risk for cerebrovascular disease, may have a role in determining clinical AD. [ABSTRACT FROM AUTHOR]