Rapid COVID-19 Screening Based on Self-Reported Symptoms: Psychometric Assessment and Validation of the EPICOVID19 Short Diagnostic Scale.

BACKGROUND: Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. Although surveys are widely used for identifying COVID-19 cases, outcomes, and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection in the general population. OBJECTIVE: We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score. METHODS: Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests. RESULTS: Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; P<.001), loss of taste and smell (365/694, 52.6% vs 239/2009, 11.9%; P<.001), and cough (352/694, 50.7% vs 580/2009, 28.9%; P<.001). With regard to subjects who underwent serological tests, IgG-positive subjects had a higher incidence of fever (65/108, 60.2% vs 43/364, 11.8%; P<.001) and pain in muscles/bones/joints (73/108, 67.6% vs 71/364, 19.5%; P<.001) than IgG-negative subjects. An analysis of self-reported COVID-19 symptom items revealed a 1-factor solution, the EPICOVID19 diagnostic scale. The following optimal scores were identified: 1.03 for respiratory problems, 1.07 for chest pain, 0.97 for loss of taste and smell 0.97, and 1.05 for tachycardia (ie, heart palpitations). These were the most important symptoms. For adults aged 18-84 years, the cutoff score was 2.56 (sensitivity: 76.56%; specificity: 68.24%) for NPS-positive subjects and 2.59 (sensitivity: 80.37%; specificity: 80.17%) for IgG-positive subjects. For subjects aged ≥60 years, the cutoff score was 1.28, and accuracy based on the presence of IgG antibodies improved (sensitivity: 88.00%; specificity: 89.58%). CONCLUSIONS: We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics.

Self-Reported Symptoms of SARS-CoV-2 Infection in a Nonhospitalized Population in Italy: Cross-Sectional Study of the EPICOVID19 Web-Based Survey.

BACKGROUND: Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce. OBJECTIVE: The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population. METHODS: EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19-like infection in the nontested population. RESULTS: A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection. CONCLUSIONS: Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.

Different Exposures to Risk Factors Do Not Explain the Inverse Relationship of Occurrence Between Cancer and Neurodegenerative Diseases: An Italian Nested Case-control Study.

Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's Diseases (AD/PD) and vice-versa. We evaluated whether a different distribution of known nongenetic risk factors for cancer and AD/PD, might explain their inverse relationship of occurrence. We nested 2 case-control studies in a subsample of a large cohort of 1,000,000 resident in Lombardy Region in Italy (n=1515), followed-up for cancer and AD/PD occurrence since 1991 until 2012. Conditional logistic regression was performed to determine the odds ratios (OR) and 95% confidence intervals (CI) of AD/PD in subjects with and without cancer and the risk of cancer in those with and without AD/PD. A total of 54 incident cases of AD/PD and 347 cancer cases were matched with 216 and 667 controls, respectively. After controlling for low education, obesity, history of hypertension, diabetes, dyslipidemia, physical activity, smoking habit, alcohol consumption, and dietary habit, cancer was found inversely associated with the risk of AD/PD (OR, 0.66; 95% CI, 0.32-1.38), and the risk of cancer in AD/PD was similarly reduced (OR, 0.42; 95% CI, 0.20-0.91). Different exposures to nongenetic risk factors of both diseases do not explain their competitive relationship of occurrence.

Inverse occurrence of cancer and Alzheimer disease: a population-based incidence study.

OBJECTIVE: To evaluate the incidence of cancer in persons with Alzheimer disease (AD) and the incidence of AD dementia in persons with cancer. METHODS: This was a cohort study in Northern Italy on more than 1 million residents. Cancer incidence was derived from the local health authority (ASL-Mi1) tumor registry and AD dementia incidence from registries of drug prescriptions, hospitalizations, and payment exemptions. Expected cases of AD dementia were calculated by applying the age-, sex-, and calendar year-specific incidence rates observed in the whole population to the subgroup constituted of persons with newly diagnosed cancers during the observation period (2004-2009). The same calculations were carried out for cancers in patients with AD dementia. Separate analyses were carried out for the time period preceding or following the index diagnosis for survivors and nonsurvivors until the end of 2009 and for different types and sites of cancer. RESULTS: The risk of cancer in patients with AD dementia was halved, and the risk of AD dementia in patients with cancer was 35% reduced. This relationship was observed in almost all subgroup analyses, suggesting that some anticipated potential confounding factors did not significantly influence the results. CONCLUSIONS: The occurrence of both cancer and AD dementia increases exponentially with age, but with an inverse relationship; older persons with cancer have a reduced risk of AD dementia and vice versa. As AD dementia and cancer are negative hallmarks of aging and senescence, we suggest that AD dementia, cancer, and senescence could be manifestations of a unique phenomenon related to human aging.

Position paper of the Italian Society for the study of Dementias (SINDEM) on the proposal of a new lexicon on Alzheimer disease.

A panel of Italian neurologists of the Italian Society for the study of Dementias (SINDEM) discussed the recently proposed new lexicon for Alzheimer disease (AD) and the related diagnostic criteria for the different phases of the disease (Preclinical AD, prodromal AD and Alzheimer's dementia) (Dubois et al. in Lancet Neurol 6:734-746, 2007; in Lancet Neurol 9:1118-1127, 2010). The aim of this discussion was to reach a consensus, among the Italian neurologists involved in the study and care of persons with dementia, in particular in reference to the potential use of the proposed diagnostic criteria in clinical practice. After having critically revised the scientific evidence related to the new lexicon and to the new proposed diagnostic criteria, the panel concluded that the proposed new diagnostic criteria and the new proposed lexicon for AD are conceptually attractive. However, the evidence about the instrumental and laboratory markers for the diagnosis of the preclinical and asymptomatic states of the disease are, until to now, insufficient to support the routine clinical use of these investigations.

Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD.

Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degeneration (FTLD) by haploinsufficiency mechanism, although their effects on brain tissue dysfunction and damage still remain to be clarified. In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the DMN. Our findings suggest that compensatory mechanisms of brain plasticity are present in GRN-related FTLD, but with different patterns at a preclinical and symptomatic disease stage.

Association between prescription of conventional or atypical antipsychotic drugs and mortality in older persons with Alzheimer's disease.

BACKGROUND/AIMS: To evaluate whether dementia patients prescribed antipsychotic drugs have a higher mortality compared to unexposed patients, and to investigate whether there are differences in mortality associated with exposure to conventional versus atypical antipsychotic drugs. METHODS: Retrospective population cohort study with information gathered from the Italian Health Information System. All 4,369 residents of Milan (Italy) aged 60 years or older who were newly prescribed an antidementia drug (donepezil, rivastigmine or galantamine) from January 2002 to June 2008 were included. All new users of antipsychotic drugs in this cohort were categorized according to conventional (n = 156) or atypical (n = 806) drug exposure. The mortality risks of users of conventional or atypical antipsychotics compared to nonusers were evaluated with survival analysis, considering exposure to antipsychotic drugs as a time-dependent variable. RESULTS: Mortality was increased two- and fivefold in users of atypical and conventional antipsychotics, respectively, with respect to nonusers. CONCLUSIONS: Dementia patients prescribed antipsychotic drugs had a higher risk of death. This risk was highest for those prescribed conventional antipsychotics. At least part of the excess mortality may be due to the underlying neuropsychiatric symptoms that prompted the use of antipsychotics rather than a direct medication effect.

Relationship between cognitive impairment and behavioural disturbances in Alzheimer's disease patients.

BACKGROUND AND AIMS: Alzheimer's disease (AD) is a neurodegenerative disorder in which the patients can exhibit some behavioural disturbances in addition to cognitive impairment. The aims of the present study were to investigate the relationship between severity and rate of decline of the cognitive and behavioural impairment in patient with AD. METHODS: 54 AD patients were assessed at baseline and after 12 months with the Mental Deterioration Battery (MDB), the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) and the Neuropsychiatric Inventory (NPI-10). RESULTS: MDB was more accurate than ADAS-Cog in the early diagnosis of AD. Conversely, ADAS-Cog was more sensitive at revealing the progression of cognitive decline. Depression, Apathy and Anxiety are the most frequent and severe behavioural disturbances at baseline. At follow-up Delusions and Irritability increased significantly. Significant correlations were observed between severity of cognitive impairment and behavioural disorders both at baseline and in the progression rate passing from T0 to T12. CONCLUSIONS: Severity and progression rate of behavioural and cognitive alterations in patients with AD are significantly associated.

Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease.

OBJECTIVES: Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. DESIGN: Cross-sectional, multicenter, clinical study. PARTICIPANTS: A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. MEASUREMENTS: All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. RESULTS: Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N = 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N = 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. CONCLUSIONS: The authors' study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms.

Predictors of progression of cognitive decline in Alzheimer's disease: the role of vascular and sociodemographic factors.

Rates of disease progression differ among patients with Alzheimer's disease, but little is known about prognostic predictors. The aim of the study was to assess whether sociodemographic factors, disease severity and duration, and vascular factors are prognostic predictors of cognitive decline in Alzheimer's disease progression. We conducted a longitudinal clinical study in a specialized clinical unit for the diagnosis and treatment of dementia in Rome, Italy. A total of 154 persons with mild to moderate Alzheimer's disease consecutively admitted to the dementia unit were included. All patients underwent extensive clinical examination by a physician at admittance and all follow-ups. We evaluated the time-dependent probability of a worsening in cognitive performance corresponding to a 5-point decrease in Mini-Mental State Examination (MMSE) score. Survival analysis was used to analyze risk of faster disease progression in relation to age, education, severity and duration of the disease, family history of dementia, hypertension, hypercholesterolemia, and type 2 diabetes. Younger and more educated persons were more likely to have faster Alzheimer's disease progression. Vascular factors such as hypertension and hypercholesterolemia were not found to be significantly associated with disease progression. However, patients with diabetes had a 65% reduced risk of fast cognitive decline compared to Alzheimer patients without diabetes. Sociodemographic factors and diabetes predict disease progression in Alzheimer's disease. Our findings suggest a slower disease progression in Alzheimer's patients with diabetes. If confirmed, this result will contribute new insights into Alzheimer's disease pathogenesis and lead to relevant suggestions for disease treatment.

Rivastigmine in Alzheimer's disease: Cognitive function and quality of life.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and functional abilities associated with various behavioral disturbances. Its impact on public health and society as a whole is devastating. Slowing of the cognitive impairment, and improvements in disease duration, self-sufficiency and behavioral disturbances represent the best outcomes of pharmacologic therapy. Cholinesterase inhibitors (ChE-I) have been shown to be effective in treating the cognitive, behavioral, and functional deficits of AD. Rivastigmine is a dual inhibitor of both acetylcholine esterase (AChE) and butyrylcholinesterase (BuChE), enzymes involved in the hydrolysis of acetylcholine. Although this drug has been shown to be beneficial in patients with AD, its benefits are limited and their long-term effectiveness has not been well demonstrated.

[Variability of efficacy measures in Alzheimer's disease]. / Variabilita nelle misure di efficacia per la malattia di Alzheimer.

The efficacy of medical interventions is their capacity of inducing positive modifications of the natural history of diseases. The natural history of dementia is marked by specific events related to the cognitive and functional decline, but their occurrence is poorly predictable in individual patients being highly variable from patient to patient. For this reason it is difficult that the modest efficacy of available interventions for dementia, or their entity measured by clinical scales, may be perceived in clinical practice or in observational studies. Moreover in randomized clinical studies, the effect of this variability, in analogy to misclassification of exposition and/or disease in case control or cohort epidemiological studies, is that of an underestimation of the true efficacy of interventions.

Alzheimer's disease and frontal variant of frontotemporal dementia-- a very brief battery for cognitive and behavioural distinction.

The aim of this study was to investigate whether a brief neuropsychological battery consisting of a limited number of cognitive tests and an evaluation of the behavioural domains intended to discriminate between frontotemporal dementia (fv-FTD) and Alzheimer's disease (AD), constitutes a useful instrument for making a differential clinical diagnosis between these two pathologies. Nineteen fv-FTD and 39 AD patients were compared on cognitive tasks (assessing memory, executive functions, language and constructional praxis) and on the NPI behavioural assessment. A stepwise discriminant analysis was performed to identify the linear combination of cognitive and behavioural measures able to best discriminate between the two groups. One test for each of the investigated cognitive domains (Delayed Prose Recall, FAS verbal fluency, Boston naming test, Rey's Figure A Copy) and the four subscales of the Neuropsychiatry Inventory (NPI) which best differentiated between fv-FTD and AD patients (apathy, disinhibition, euphoria, aberrant motor behaviour) were used. The analysis selected Rey's Figure A Copy, FAS verbal fluency and NPI apathy subscale as the best discriminants between fv-FTD and AD patients. The final equation assigned 73.7% of the fv-FTD patients and 94.7% of the AD patients to the correct diagnostic group. A validation study conducted on a new independent sample of 11 fv-FTD and 22 AD patients confirmed the high sensitivity (82.6 %) and specificity (81.8%) of the diagnostic equation in assigning fv-FTD and AD patients to the correct dementia group. Although both cognitive and behavioural differences exist between FTD and AD, previous studies have aimed at differentiating the two pathologies by considering the two aspects separately and discriminant analyses were focused only on neuropsychological or neuropsychiatric evaluations. The present results emphasise the importance of rating both cognitive and behavioural clinical features of the two syndromes as objectively as possible to improve differential diagnostic accuracy.

The Caregiver Burden Inventory in evaluating the burden of caregivers of elderly demented patients: results from a multicenter study.

BACKGROUND AND AIMS: The burden perceived by caregivers of patients with dementia is a fundamental prognostic aspect in the history of the disease. The aim of this study was to demonstrate the internal consistency of the Caregiver Burden Inventory (CBI), a scale used to quantify burdens in different aspects of a caregiver's life, and the influence of patients' and caregivers' characteristics on its different dimensions. METHODS: In this cross-sectional study, 419 demented patients and their caregivers were evaluated in 16 geriatric centers in Italy. Cognitive status and behavioral disturbances were assessed by the Mini Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI), respectively. Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were also evaluated. Comorbidity was assessed by the Cumulative Illness Rating Scale (CIRS). The severity of dementia was evaluated by the Clinical Dementia Rating (CDR) score. Caregiver distress due to the behavioral problems of the patient was assessed by the Neuropsychiatric Inventory-Distress, a subscale of the NPI which evaluates stress caused by each behavioral disturbance of the patient, and by the Brief Symptom Inventory which evaluates anxiety and depression. Burden was evaluated by the CBI. RESULTS: The CBI showed very high internal consistency (Cronbach's alpha value > 0.80). Factor analysis showed that the items clustered into four dimensions, and not five as originally proposed. Multiple regression analysis revealed that patients' behavioral disturbances and disability were the major predictors of the time-dependent burden; the psychophysical burden was explained mainly by caregiver anxiety and depression. CONCLUSIONS: The CBI proved to be an effective multidimensional tool for evaluating the impact of burden on many aspects of caregivers' lives.

CCR2-64I polymorphism and CCR5Delta32 deletion in patients with Alzheimer's disease.

Monocyte chemoattractant protein-1 (MCP-1) and RANTES, as well as their related receptors, have been shown to be involved in Alzheimer's disease (AD) pathogenesis. Genes for their related receptors, CCR2 and CCR5, respectively, are characterized by the presence of two polymorphisms: a conservative change of a valine with an isoleucine at codon 64 of CCR2 (CCR2-64I) and a 32-bp deletion in the coding region of CCR5 (CCR5Delta32), which leads to the expression of a nonfunctional receptor. The distribution of the CCR2-64I and CCR5Delta32 polymorphisms was determined in 290 AD patients and in 222 controls. A decreased frequency and an absence of homozygous for the polymorphism CCR2-64I were found, thus suggesting a protective effect of the mutated allele on the occurrence of AD. However, these findings must be cautiously interpreted as the overall significance was found without adjustment for multiple comparisons and is coming from the complete absence of the genotype 64I/64I in AD patients. Conversely, no different distribution of the CCR5Delta32 deletion in the two populations was shown. Stratifying by the presence of ApoE varepsilon4 allele, gender or age at onset, no differences in either allele frequencies were observed.

MCP-1 in Alzheimer's disease patients: A-2518G polymorphism and serum levels.

MCP-1 levels are increased in CSF of patients with Alzheimer's disease (AD) compared with controls, suggesting a role in the development of dementia. Recently, a biallelic A/G polymorphism in the MCP-1 promoter at position -2518 has been found, influencing the level of MCP-1 expression in response to an inflammatory stimulus. The distribution of the A-2518G SNP was determined in 269 AD patients and in 203 healthy age matched controls, showing no differences between the two groups. On the contrary, a significant increase of MCP-1 serum levels in AD patients carrying at least one G mutated allele was observed. Moreover, the highest peaks of MCP-1 serum levels were present in patients carrying two G alleles. Stratifying by ApoE genotype, gender or age at onset, no differences in both allele frequency and MCP-1 serum concentration were observed. The A-2518G polymorphism in MCP-1 gene does not seem to be a risk factor for the development of AD, but its presence correlates with higher levels of serum MCP-1, which can contribute to increase the inflammatory process occurring in AD.

Intentional and automatic measures of specific-category effect in the semantic impairment of patients with Alzheimer's disease.

The breakdown of semantic knowledge relative to living and non-living categories was studied in patients with Alzheimer's disease (AD). The same living and non-living items were used in a semantic battery and in a semantic priming paradigm exploring automatic access to the semantic system. Although AD patients showed a semantic deficit on the intentional semantic battery, they demonstrated normal semantic facilitation on the priming task. In the AD group as a whole, the semantic impairment did not preferentially affect the living category either in the intentional or automatic condition. Instead, a prevalent deficit for the living category was found in three AD patients (14% of the group) on the intentional semantic tasks, but not on the automatic one. These findings support the view that the category effect may not be a generalised phenomenon in AD but may be restricted to a limited number of patients. The intentional/automatic dissociation of the semantic breakdown demonstrated by AD patients is discussed in relation to different theories regarding the organisation of semantic memory.

Serum cholesterol levels modulate long-term efficacy of cholinesterase inhibitors in Alzheimer disease.

The clinical, genetic or biological variables which regulate long-term efficacy of cholinesterase inhibitors (ChEIs) in Alzheimer disease (AD) are still unknown and it is not possible to predict who will benefit from the treatment. In this study we showed that high cholesterol levels correlated with faster decline at 1-year follow-up in AD patients on ChEIs. These findings suggest that serum cholesterol is a modulating factor of treatment response and additional therapies aimed at reducing treatable high cholesterol levels may represent an alternative strategy to improve ChEIs efficacy and slow down disease progression over time.

Clinical pharmacology of anti-Alzheimer drugs.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and functional abilities, associated with various degrees of behavioural disturbances, with a devastating impact on public health and on the whole society. Slowing of cognitive impairment, duration of disease, self-sufficiency and behavioural disturbances represent the best outcomes of the pharmacologic therapy. Cholinesterase inhibitors (ChE-I) have been shown to be effective in the treatment of the cognitive, behavioural, and functional deficits of AD. In addition to ChE-I, a number of studies have been carried out to investigate the possible use of other compounds and pharmacologic strategies; more compounds, postsynaptic muscarinic and nicotinic receptor agonists, are under investigation. The standard suggested care for pharmacologic management of the cognitive and functional disabilities of AD at present consists of treatment with ChE-I. Practice recommendations and treatment guidelines are derived from clinical trials.

Abnormalities in the pattern of platelet amyloid precursor protein forms in patients with mild cognitive impairment and Alzheimer disease.

CONTEXT: Patients affected by sporadic Alzheimer disease (AD) show a significant alteration of amyloid precursor protein (APP) forms in platelets when compared with patients with dementia but without AD and age-matched controls. OBJECTIVE: To evaluate the ratio of platelet APP forms (APPr) in early-stage AD and mild cognitive impairment (MCI) and its potential as a biomarker for the early identification of AD. SETTING: Community population-based sample of patients admitted to 4 AD centers for investigation of cognitive disturbances. DESIGN AND METHODS: Thirty-five patients with mild AD (mAD), 21 patients with very mild AD (vmAD), 30 subjects with MCI, and 25 age-matched controls were included. The APPr was evaluated by Western blot analysis in platelet homogenate. RESULTS: Compared with controls (mean +/- SD, 0.93 +/- 0.3), the mean APPr was decreased in patients with mAD (0.44 +/- 0.24; P<.001) and patients with vmAD (0.49 +/- 0.3; P<.001). Regarding the MCI group, a significant decrease in APPr was found compared with controls (0.62 +/- 0.33; P<.001). Fixing a cutoff score of 0.6, sensitivity was 88.6% (31/35) for patients with mAD and 85.7% (18/21) for patients with vmAD, whereas specificity was 88% (22/25) for controls. Among patients with MCI, 18 (60%) of 30 individuals displayed APPr values below the cutoff. CONCLUSIONS: Alteration of platelet APP forms is an early event in AD, and the measurement of APPr may be useful for the identification of preclinical AD in patients with MCI.