Rates Of Cognitive Impairment Research Articles

Carnitine metabolites and cognitive improvement in patients with schizophrenia treated with olanzapine: a prospective longitudinal study.

Objective: Cognitive impairment is one of the core symptoms of schizophrenia, which is stable and lifelong. L-carnitine has been shown to improve cognitive function and decrease the rate of cognitive deterioration in patients with Alzheimer's disease. However, it remains unclear regarding the role of L-carnitine and its metabolites in cognitive functions in schizophrenia after treatment with olanzapine. The purpose of this study was to evaluate the relationship between changes in plasma levels of L-carnitine metabolites and cognitive improvement after olanzapine treatment. Methods: This was a prospective longitudinal study. In this study, we recruited 25 female patients with first episode schizophrenia (FES) who were drug naïve at baseline and received 4 weeks of olanzapine monotherapy. Cognitive function was assessed at baseline and 4-week follow-up using the RBANS. Plasma L-carnitine metabolite levels were determined by a metabolomics technology based on untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Results: We found that the immediate memory index, delayed memory index and RBANS composite score were significantly increased at the 4-week follow-up after treatment. A total of 7 differential L-carnitine metabolites were identified in FES patients after olanzapine monotherapy. In addition, we found that changes in butyrylcarnitine were positively correlated with improvements in language index and RBANS composite score. Further regression analyses confirmed the association between reduced butyrylcarnitine levels and cognitive improvement after olanzapine monotherapy in FES patients. Conclusion: Our study shows that cognitive improvement after olanzapine treatment was associated with changes in L-carnitine metabolite levels in patients with FES, suggesting a key role of L-carnitine in cognition in schizophrenia.

Czynniki sercowo - naczyniowe w zaburzeniach otępiennych

Dementia affects a significant portion of the population of elderly people and thus has become one of the most important health problems. At the same time, people with dementia are more likely to be also affected by concomitant diseases. Cardiovascular factors seem to be of particular importance. It has been shown that problems regarding blood pressure as well as lipid and carbohydrate metabolism play a crucial role for the rate of cognitive deterioration in elderly individuals in both vascular cognitive impairments and primary degenerative impairments (e.g., Alzheimer's disease). A clear relationship is observed between vascular pathology and degenerative processes in the brain. The period of life in which the exposure to cardiovascular factors occurs seems to be key, and these relationships are best documented in middle age. With aging, their importance as factors accelerating the progression of cognitive impairments seems to diminish, especially in Alzheimer-type dementia. Research on the importance of comorbidity in dementia processes may be crucial for the development of prevention and therapy programs for dementia.

Effects of an art-based intervention in older adults with mild cognitive impairment: a randomised controlled trial.

Art-based interventions may delay cognitive decline and improve health-related outcomes in older adults with mild cognitive impairment (MCI). To examine the effects of the Creative Expressive Arts-based Storytelling (CrEAS) program compared to active and waitlist controls on neurocognitive and other health-related outcomes in older people with MCI. Three-arm parallel-group, randomised controlled design. One-hundred and thirty-five adults with MCI (mean age: 70.93 ± 6.91years). Participants were randomly assigned to intervention (CrEAS, n = 45), active control (n = 45) or waitlist control (n = 45) groups. Interventions were applied once per week for 24weeks. The primary outcome was global cognitive function; secondary outcomes were specific cognition domains (memory, executive function, language and attention) and other health-related outcomes (anxiety, depression and quality of life [QoL]). All variables were measured at baseline (T0), 24-week follow-up (T1) and 48-week follow-up (T2). Participants in the CrEAS group showed significantly higher global cognitive function (adjusted mean difference [MD] = -0.905, 95% confidence interval [CI] -1.748 to -0.062; P = 0.038) and QoL (adjusted MD = -4.150, 95% CI -6.447 to -1.853; P = 0.001) and lower depression symptoms (adjusted MD = 2.902, 95% CI 0.699-5.104; P = 0.011) post-intervention at the 24-week follow-up compared with the active control group. At 48-week follow-up, only the Auditory Verbal Learning Test Immediate recall score was significantly improved compared with the active control group (adjusted MD = -2.941, 95% CI -5.262 to -0.620; P = 0.014). Older adults with MCI who participated in the CrEAS program improved their neuropsychological outcomes and QoL and reduced their rate of cognitive deterioration.

Neuropsychiatric Inventory-Questionnaire Assessed Nighttime Behaviors in Cognitively Asymptomatic Patients with Pathologically Confirmed Alzheimer's Disease Predict More Rapid Cognitive Deterioration.

The temporal relationship between sleep, Alzheimer's disease (AD), and cognitive impairment remains to be further elucidated. First, we aim to determine whether the Neuropsychiatric Inventory-Questionnaire (NPI-Q) assessed nighttime behaviors prior to cognitive decline influence the rate of cognitive deterioration in pathologically confirmed AD, and second, to assess the possible interactions with APOE allele and cerebral amyloid angiopathy (CAA). The rate of cognitive decline between cognitively asymptomatic participants from the National Alzheimer Coordinating Center who eventually received a neuropathologic diagnosis of AD with (+NTB) or without (-NTB) nighttime behaviors were compared using independent samples t-test. Participants were stratified by APOE carrier and CAA status. Demographic and patient characteristics were assessed using descriptive statistics, and the independent samples t-test was used for continuous variables and chi-square test for categorical variables. The significance level was set at p≤0.05. The rate of cognitive decline was greater in +NTB (n = 74; 3.30 points/year) than -NTB (n = 330; 2.45 points/year) (p = 0.016), even if there was no difference in cognitive status at onset. This difference was restricted to APOE ɛ4 carriers (p = 0.049) and positive CAA participants (p = 0.020). Significance was not reached in non-carriers (p = 0.186) and negative CAA (p = 0.364). APOE and CAA were not differentially distributed between the NTB groups. NPI-Q assessed nighttime behaviors, a surrogate for sleep disturbances, are associated with more rapidly deteriorating cognition in patients with AD neuropathology who are also carriers of APOE ɛ4 or show CAA.

The Rate of Decrease in Brain Perfusion in Progressive Supranuclear Palsy and Corticobasal Syndrome May Be Impacted by Glycemic Variability-A Pilot Study.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are tauopathic parkinsonian syndromes, presently lacking disease-modifying treatments. Patients affected by these diseases suffer due to multidimensional deteriorations resulting in motor and cognitive impairment. Previously published research has confirmed risk factors that may impact the course of PSP and CBS, among them hypertension and diabetes. Less data is available regarding prediabetes and glycemic variability. In this study, 26 patients with clinical diagnoses of PSP and CBS were examined using glycated hemoglobin and perfusion single-photon emission tomography (SPECT). Patients were divided into two groups—PSP/CBS patients with glycated hemoglobin (HbA1c) below and above 5.7%. The results of the perfusion evaluation were compared with the values from healthy volunteers from the software's database. A decrease in perfusion in certain regions of interest was observed among patients affected by increased glycemic variability. A more pronounced decrement in perfusion was observed only in some regions of interest—the hippocampus, pons, left thalamus, right insula. The results indicated that, among PSP/CBS patients, individuals with more pronounced glycemic variability had more severe hypoperfusion in certain brain regions in comparison with PSP/CBS patients without carbohydrate metabolism disorders. Due to the fact that PSP and CBS are associated with cognitive impairment, an additional decrease in perfusion in the hippocampal area may impact the rate of cognitive deterioration.

Sleep disturbances in cognitively asymptomatic patients with histopathologically confirmed AD predict rapid cognitive deterioration

AbstractBackgroundThe temporal relationship between sleep disturbances, Alzheimer’s Disease (AD) pathology, and related cognitive impairment remains controversial. The objective of this study is to determine whether sleep disturbances at baseline predict the rate of cognitive deterioration in cognitively intact subjects with autopsy confirmed AD neuropathology. We also examine the interaction of sleep disturbances with APOE genotype and cerebral amyloid angiopathy (CAA).MethodThe National Alzheimer’s Disease Coordinating Center (NACC) datasets was used to compare the rate of cognitive decline between subjects with nighttime behaviors [(+)NTB] or without [(‐)NTB] at baseline as assessed by the Neuropsychiatric Inventory Questionnaire Quick Version (NPI‐Q). Cognitive impairment was determined by the Mini‐Mental Status Examination (MMSE) total score. Cognitively normal subjects at baseline were defined as having an initial MMSE score ≥ 24 at the first NACC clinical visit. The rate of cognitive decline was determined based on the individual’s annual MMSE score change over the total clinical visits made. All subjects had a primary neuropathologic diagnosis of Alzheimer’s pathology as determined by both high CERAD score and Braak stage.Result404 subjects fulfilled the inclusion criteria. The rate of cognitive decline was greater in (+)NTB (74 cases; 3.30 points per year) compared to (‐)NTB (330 cases; 2.45 points per year) (p = 0.016). This significant difference was restricted to APOE ε4 carriers (p = 0.049) and subjects with CAA (p = 0.020), and was absent in non e4 carriers and subjects without CAA. There was no difference between (+)NTB and (‐)NTB in the prevalence of these two factors associated with the rate of cognitive decline (e4 and CAA), suggesting that NTB itself is responsible for the effect observed.ConclusionNPI‐Q assessed nighttime behaviors, a surrogate for sleep disturbances, are associated with more rapidly declining cognition in subjects with Alzheimer’s neuropathology. In addition, this relationship is enhanced in carriers of APOE e4 and cerebral amyloid angiopathy.

Sex and gender differences in Alzheimer's disease: current challenges and implications for clinical practice: Position paper of the Dementia and Cognitive Disorders Panel of the European Academy of Neurology.

Alzheimer's disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual's sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology.

Cognitive disparities between US- and foreign-born individuals

This study aims to assess whether heterogeneity in cognitive functioning trajectories differ across racial/ethnic and nativity (REN) groups, as well as if gender, level of education, physical comorbidities, history of health behaviors, and functional limitations reflect the processes associated with cumulative advantage (disadvantage), persistent inequality, and age as leveler. The empirical work of this study is based on the 1996–2012 Health and Retirement Study (HRS). Growth curve modeling is used to assess the aims of this study. Long-term change in cognitive functioning trajectories are shaped along REN lines. US-born whites have significantly better cognitive function but experience a faster rate of cognitive deterioration than foreign-born whites, as well as foreign- and US-born blacks, Mexicans, other Hispanics, and other racial ethnic groups, even after taking gender, level of education, health behaviors, and the relevant chronic and physical health conditions into account. There is a pressing need for more culturally appropriate and culturally adapted programs and preventive strategies that take the cultural, linguistic, and other specific needs and issues of individuals in different REN groups into account. There remains a pressing need for an integrated treatment and screening for physical comorbidities, functional limitations, and cognitive interventions.

Biomarkers for Alzheimer's disease: current status and prospects for the future.

Accumulating data from the clinical research support that the core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau) reflect key elements of AD pathophysiology. Importantly, a large number of clinical studies very consistently show that these biomarkers contribute with diagnostically relevant information, also in the early disease stages. Recent technical developments have made it possible to measure these biomarkers using fully automated assays with high precision and stability. Standardization efforts have given certified reference materials for CSF Aβ42, with the aim to harmonize results between assay formats that would allow for uniform global reference limits and cut-off values. These encouraging developments have led to that the core AD CSF biomarkers have a central position in the novel diagnostic criteria for the disease and in the recent National Institute on Aging and Alzheimer's Association biological definition of AD. Taken together, this progress will likely serve as the basis for a more general introduction of these diagnostic tests in clinical routine practice. However, the heterogeneity of pathology in late-onset AD calls for an expansion of the AD CSF biomarker toolbox with additional biomarkers reflecting additional aspects of AD pathophysiology. One promising candidate is the synaptic protein neurogranin that seems specific for AD and predicts future rate of cognitive deterioration. Further, recent studies bring hope for easily accessible and cost-effective screening tools in the early diagnostic evaluation of patients with cognitive problems (and suspected AD) in primary care. In this respect, technical developments with ultrasensitive immunoassays and novel mass spectrometry techniques give promise of biomarkers to monitor brain amyloidosis (the Aβ42/40 or APP669-711/Aβ42 ratios) and neurodegeneration (tau and neurofilament light proteins) in plasma samples, but future studies are warranted to validate these promising results further.

Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer's Disease Patients During Oral Omega-3 Fatty Acid Supplementation: The OmegAD Study.

ω3 fatty acids (ω3 FAs) may slow the rate of decline in cognitive performance in mild forms of cognitive impairment and Alzheimer's disease (AD). However, the relationship between changes of plasma ω3 FA levels and cognitive performance, as well as effects of gender, are poorly known. To study the effect of 6-month administration of DHA-rich ω3 FA supplementation on plasma FA profiles in patients with mild to moderate AD in relation to cognitive performance and gender. This investigation is part of the OmegAD Study. 174 AD patients (74 ± 9 years) were randomized to a daily intake of 2.3 g ω3 FA or placebo for 6 months; subsequently all received the ω3 FA preparation for the next 6 months. Baseline as well as changes in plasma levels of the main ω3 FAs in 165 patients, while receiving ω3 FA supplementation for 6 months, were analyzed for association to cognitive performance (assessed by ADAS-cog and MMSE scores) as well as to gender. Preservation of cognitive functioning, assessed by ADAS-cog or its sub-items (but not MMSE) scores, was significantly associated to increasing plasma ω3 FA levels over time. Thus, the higher ω3 FA plasma levels rose, the lower was the rate of cognitive deterioration. This effect was not related to gender; since although females displayed higher ω3 FA plasma levels than did males after 6 months of supplementation, this difference disappeared when adjusted for body weight. Since our study suggests dose-response relationships between plasma levels of ω3 FA and preservation of cognition, future ω3 FA trials in patients with mild AD should consider exploring graded (and body weight adjusted) doses of ω3 FA.

Impact of Delirium on the Course of Alzheimer Disease

Delirium is characterized by acute cognitive impairment. We examined the association of delirium with long-term cognitive trajectories in older adults with Alzheimer disease (AD). We evaluated prospectively collected data from a nested cohort of hospitalized patients with AD (n=263) in the Massachusetts Alzheimer Disease Research Center patient registry between January 1, 1991, and June 30, 2006 (median follow-up duration, 3.2 years). Cognitive function was measured using the information-memory-concentration (IMC) section of the Blessed Dementia Rating Scale. Delirium was identified using a validated medical record review method. The rate of cognitive deterioration was contrasted using random-effects regression models. Fifty-six percent of patients with AD developed delirium during hospitalization. The rate of cognitive deterioration before hospitalization did not differ significantly between patients who developed delirium (1.4 [95% CI, 0.7-2.1] IMC points per year) and patients who did not develop delirium (0.8 [95% CI, 0.3-1.3] IMC points per year) (P=.24). After adjusting for dementia severity, comorbidity, and demographic characteristics, patients who had developed delirium experienced greater cognitive deterioration in the year following hospitalization (3.1 [95% CI, 2.1-4.1] IMC points per year) relative to patients who had not developed delirium (1.4 [95% CI, 0.2-2.6] IMC points per year). The ratio of these changes suggests that cognitive deterioration following delirium proceeds at twice the rate in the year after hospitalization compared with patients who did not develop delirium. Patients who had developed delirium maintained a more rapid rate of cognitive deterioration throughout a 5-year period following hospitalization. Sensitivity analyses that excluded rehospitalized patients and included matching on baseline cognitive function and baseline rate of cognitive deterioration produced essentially identical results. Delirium is highly prevalent among persons with AD who are hospitalized and is associated with an increased rate of cognitive deterioration that is maintained for up to 5 years. Strategies to prevent delirium may represent a promising avenue to explore for ameliorating cognitive deterioration in AD.

Delirium and Long-term Cognitive Trajectory Among Persons With Dementia

BACKGROUND Delirium is characterized by acute cognitive impairment. We examined the association of delirium with long-term cognitive trajectories in older adults with Alzheimer disease (AD). METHODS We evaluated prospectively collected data from a nested cohort of hospitalized patients with AD (n=263) in the Massachusetts Alzheimer Disease Research Center patient registry between January 1, 1991, and June 30, 2006 (median follow-up duration, 3.2 years). Cognitive function was measured using the information-memory-concentration (IMC) section of the Blessed Dementia Rating Scale. Delirium was identified using a validated medical record review method. The rate of cognitive deterioration was contrasted using random-effects regression models. RESULTS Fifty-six percent of patients with AD developed delirium during hospitalization. The rate of cognitive deterioration before hospitalization did not differ significantly between patients who developed delirium (1.4 [95% CI, 0.7-2.1] IMC points per year) and patients who did not develop delirium (0.8 [95% CI, 0.3-1.3] IMC points per year) (P=.24). After adjusting for dementia severity, comorbidity, and demographic characteristics, patients who had developed delirium experienced greater cognitive deterioration in the year following hospitalization (3.1 [95% CI, 2.1-4.1] IMC points per year) relative to patients who had not developed delirium (1.4 [95% CI, 0.2-2.6] IMC points per year). The ratio of these changes suggests that cognitive deterioration following delirium proceeds at twice the rate in the year after hospitalization compared with patients who did not develop delirium. Patients who had developed delirium maintained a more rapid rate of cognitive deterioration throughout a 5-year period following hospitalization. Sensitivity analyses that excluded rehospitalized patients and included matching on baseline cognitive function and baseline rate of cognitive deterioration produced essentially identical results. CONCLUSIONS Delirium is highly prevalent among persons with AD who are hospitalized and is associated with an increased rate of cognitive deterioration that is maintained for up to 5 years. Strategies to prevent delirium may represent a promising avenue to explore for ameliorating cognitive deterioration in AD.

MxA Polymorphisms Are Associated with Risk and Age-at-Onset in Alzheimer Disease and Accelerated Cognitive Decline in Chinese Elders

Alzheimer disease (AD) is the most common neurodegenerative disease, and inflammation has been associated with the pathogenesis of AD. The myxovirus resistance protein 1 (MxA) is an interferon-induced antiviral protein and is widely studied in virus-caused diseases. An immunohistochemical study has shown MxA expression in senile plaques of the AD brain, suggesting that MxA might be involved in the pathogenesis of AD. In this study, 10 tagged single-nucleotide polymorphisms (SNPs) and two commonly studied SNPs in the MxA gene were investigated in 220 AD patients and 316 age-matched healthy Chinese subjects to investigate the association to the predisposition and age of onset (AAO) of AD. Healthy subjects were followed up for 2 years to determine the association of MxA polymorphisms and the rate of cognitive deterioration. Our result showed rs17000900 (MxA-123) and rs461093 were significantly associated with the risk of AD. Six MxA SNPs, including MxA -123, were associated to AAO of AD. The carriers of minor alleles of five MxA SNPs, including rs457274, rs2071430 (MxA -88), rs461093, rs469083, and rs1557372, were associated with faster cognitive decline over 2 years. Furthermore, our functional assay showed significant association between increased MxA expression and the -123A/-88T haplotype, which is in line with our findings in genetic association. This is the first study showing the significant association of MxA SNPs and predisposition of AD, modulation of AAO in AD, and rate of cognitive decline.

The role of persistent and incident major depression on rate of cognitive deterioration in newly diagnosed Alzheimer's disease patients

Depression may potentially impair the clinical course of Alzheimer's disease (AD). Thus, the aim of this study was to investigate cognitive progression of AD patients with or without major depressive episode (MDE). In this 1-year longitudinal follow-up study conducted in three Italian memory clinics, 119 newly diagnosed probable AD patients of mild severity, who were not undergoing treatment with an acetyl-cholinesterase inhibitor (AChEI), and had not been treated with psychotropic drugs in the last 2years, were included. Patients were assessed to investigate the effect of baseline and 1-year follow-up MDE (using modified DSM-IV diagnostic criteria for MDE in AD) on progression of global cognitive deterioration (using Mini-Mental State Examination (MMSE)), adjusted for confounding factors. Never being depressed was associated with a 3.1 (95%CI 1.0–10.1) increased risk of MMSE decline compared to recovered depression. Six times more patients with persistent depression had MMSE decline compared to patients with recovered depression. However, the largest odds (7.3; 95%CI 1.4–38.1) of cognitive decline was observed in patients who developed incident depression over follow-up. In conclusion, persistent or incident depression worsens cognitive outcome while no or recovered depression does not affect it in early AD patients.

Comparisons of cognitive deterioration rates by dementia subtype

Pathophysiological aspects of dementia and its rate of cognitive deterioration could be dependent on disease subtype, Alzheimer's dementia (AD), vascular dementia (VaD), and Parkinson's disease with dementia (PDD). 150 patients diagnosed at the Chungnam National University Hospital (87 women and 63 men) memory clinic. The participants consisted of 68 patients with AD, 23 patients with VaD, and 59 patients with PDD, who were diagnosed by the individual criteria, respectively. Cognitive screening was evaluated using the Korean version of the mini-mental state examination (MMSE). Repeated evaluations were conducted at 6-month, 1 year, and 2 years after initial baseline assessment. Rates of cognitive decline were calculated by dividing MMSE score differences by the number of months lapsed. No difference was found between the three dementia subtypes with respect to baseline MMSE scores. Cognitive decline was not obvious up to 6-month of the follow-up, but by 12-month of follow-ups was significant regardless of the dementia subtype. Furthermore, the rate of cognitive decline in the AD group was significantly faster than in the PDD or VaD groups. This study suggests that rate of cognitive deterioration in dementia is not linear over time and that dementia subtypes have different rates of cognitive deterioration.

Use of standard tests to predict the rate of cognitive deterioration in patients with Alzheimer's disease: A one-year prospective study

Use of standard tests to predict the rate of cognitive deterioration in patients with Alzheimer's disease: A one-year prospective study

The progression of cognitive deterioration and regional cerebral blood flow patterns in Alzheimer's disease: A longitudinal SPECT study

Background and purpose The progression of cognitive deterioration in patients with Alzheimer's disease (AD) is considerably variable. The ability to predict the progression rate is important for clinicians to treat and manage patients with AD. We examined the possible relationship between the rate of cognitive deterioration and regional cerebral blood flow (rCBF) patterns in patients with AD. Methods We followed 48 patients with AD for an average of 37 months. They were subsequently divided into the rapidly progressing group ( n = 24) and slowly progressing group ( n = 24) based on an annual Mini-Mental State Examination (MMSE) score change. Initial and follow-up rCBF were assessed using single photon emission CT (SPECT) and the SPECT data were analyzed by 3D-stereotactic surface projections. Results At initial evaluation, the rapidly progressing group had greater rCBF deficits mainly in the parietotemporal and frontal regions, and left posterior cingulate than did the slowly progressing group. When compared with initial SPECT, follow-up SPECT showed a significant rCBF reduction in widespread regions, including parietotemporal and frontal lobes, of the rapidly progressing group, while showed in the scattered and small regions of hemispheres of the slowly progressing group. Conclusion Our longitudinal SPECT study suggests a significant association between rCBF deficits in the parietotemporal, posterior cingulate, and frontal regions and subsequent rapid cognitive and rCBF deterioration.

The D&T Report

The D&T Report

Elevated Plasma Levels of α -1-Anti-Chymotrypsin in Age-Related Cognitive Decline and Alzheimers Disease: A Potential Therapeutic Target

alpha-1-antichymotrypsin (ACT), is an acute phase protein and a protease inhibitor produced by the liver and brain. ACT is involved in the pathogenesis of Alzheimer's disease (AD), since elevated ACT concentration was found in cerebrospinal fluid (CSF) and brain from AD. ACT has also been shown to influence amyloid deposition in vitro and in animal models of AD. In this investigation 830 healthy controls, 69 subjects with cognitive impairment and not dementia (CIND), 53 patients with severe clinical AD and 142 patients with mild AD were investigated. Plasma levels of ACT were measured with a new competitive immune enzyme linked immune-assay (ELISA). ACT levels were higher in AD patients than in CIND or controls. An age dependent increase of plasma ACT was present in both healthy elderly and CIND. Patients with mild clinical AD were followed up for two years and stratified according to the rate of clinical deterioration. CT plasma levels were elevated in AD patients that showed an accelerated rate of cognitive deterioration during the follow up; this increment being prominent in AD with the Apolipoprotein E (APOE) epsilon 4 allele. Therefore, increased peripheral ACT levels in APOE 4 positive patients appear to predict an accelerated clinical progression. Plasma ACT might be used as a surrogate marker to monitor the conversion of pre-dementia stages to AD and the progression of the disease. The development of compounds able to interfere with the ACT biological activity (protease inhibition and/or promotion of amyloid deposition) might have therapeutic relevance for the disease.

S4-01-01: Identification of subgroups of Alzheimer disease

S4-01-01: Identification of subgroups of Alzheimer disease