Relación de las cinéticas del PSA en la detección de la recurrencia del cáncer de próstata post prostatectomía radical con la 18f-colina tomografía por emisión de positrones/tomografía computada [PET/TC colina (PETC)] / Kinetic Relation Between PSA and 18F-choline PET/ CT in the Detection of Recurrent Prostatic Cancer After Radical Prostatectomy

Resumen Objetivo: El objetivo de este estudio es evaluar la relación de las cinéticas del antígeno prostático específico (PSA por su sigla en inglés) con la positividad de la tomografía por emisión de positrones/tomografía computada [PET/TC colina (PETC)]en pacientes con una recaída de cáncer de próstata (RCP). Materiales y métodos: Se realizó un trabajo retrospectivo de 48 pacientes con RCP post prostatectomía radical (PR) evaluados con PETC. Resultados: La PETC negativa tuvo una mediana de 16,3 meses y la PETC positiva de 5,5 meses (p = < 0,001) para el tiempo de doblaje de PSA (PSADT por su sigla en inglés); la PETC fue positiva en el 96% de los pacientes con un PSADT< 12 meses. La PETC negativa tuvo una mediana de 0,03 ng/ml/año y la PETC positiva de 4,1 ng/ml/año (p = < 0,001) para la velocidad del PSA (PSAVpor su sigla en inglés); la PETC fue positiva en el 92% de los pacientes con un PSAV > 0,75 ng/ml/año. Las áreas bajo la curva ROC para PSAV fue de 0,984 con un punto de corte de mayor discriminación de 0.785 ng/ml/año, mostrando razones de verosimilitud (LR por su sigla en inglés) LR + = 25 y LR- = 0,1. Para PSADT el ROC fue de 0,992 con un punto de corte de mayor discriminación de 11 meses, mostrando LR + = 11 y LR- = 0. Discusión: El PSA es un indicador inespecífico de PETC positiva. Un estudio inicial demostró que los pacientes con una RCP con una PETC positiva tenían un menor PSADT y una mayor PSAV que los pacientes con una PETC negativa. Conclusión: La positividad de la PETC se vio influenciada por las cinéticas del PSA, observándose que a menor PSADT y que a mayor PSAV mayor fue la probabilidad de la positividad de la PETC.

Abstract Purpose: The aim of this study is to evaluate the relationship between Prostate-Specific Antigen (PSA) kinetics and the detection of Prostate Cancer Relapse (PCR) with Positron-Emission Tomography (PETC). Material and methods: A retrospective study of 48 patients with a PCR after a radical prostatectomy evaluated with PETC was performed. Results: PSA Doubling Time (PSADT), with negative PETC, had a median of 16.3 months and the positive PETC a median of 5.5 months (p = < 0.001); 96% of patients with a PSADT <12 months had positive PETC. PSA Velocity (PSAV), negative PETC, had a median of 0.03 ng/ml/year and positive PETC a median of 4.1 ng/ml/year (p = < 0.001); 92% of patients who had a PSAV > 0.75 ng/ml/year had positive PETC. The ROC for PSAV was 0.984 with a cut-off value of 0.785 ng/ml/year, Showing Likelihood Ratios (LR) LR + = 25 and LR- = 0.1. The ROC for PSADT was 0.992 with a cut off value of 11 months, showing LR + = 11 and LR- = 0. Discussion: PSA is a nonspecific indicator of positive PETC. An initial study demon-strated that patients with a PCR and positive PETC had lower PSADT and higher PSAV than patients with a negative PETC. Conclusion: The rate of detection of PCR with PETC was influenced by the kinetics of PSA, and it was observed that the lower the PSADT and the higher the PSAV, the greater the probability of the positivity of the PETC.

From Subjective Cognitive Decline to Alzheimer's Disease: The Predictive Role of Neuropsychological Assessment, Personality Traits, and Cognitive Reserve. A 7-Year Follow-Up Study.

The aim of this study was to evaluate the accuracy of neuropsychological assessment in predicting conversion from subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the effect of personality traits and cognitive reserve in progression from SCD to MCI. As part of a longitudinal, clinical-neuropsychological-genetic survey on SCD and MCI, 284 patients referred to our hospital between 1990 and 2017 were included. All patients underwent clinical-extensive neuropsychological evaluation and Apolipoprotein E genotyping; personality traits were assessed in a subgroup. Each patient underwent clinical-neuropsychological follow-up. Subjects with a follow-up shorter than two years were excluded. A total of 212 subjects were, after exclusions, considered: 26 out of 109 SCD subjects progressed to MCI (SCD-p), 15 converted to AD (SCD-c), and 68 remained stable (SCD-s). Of 103 MCI subjects, 39 converted to AD (MCI-c) and 64 remained stable (MCI-s). At baseline, SCD-c performed significantly worse than SCD-s in tests assessing long-term verbal memory. MCI-c showed worse performance on neuropsychological tests for short- and long-term verbal memory and for ecological evaluation of memory (RBMT). These tests provided good accuracy in distinguishing MCI-c and MCI-s. Emotional stability was significantly lower in SCD-s than in SCD-p while higher intellectual activities were associated with a lower risk of conversion to MCI. Our results suggest that memory neuropsychological tests may represent a reliable tool to estimate the risk of progression to AD. Personality and lifestyle factors could provide useful information to identify SCD subjects who may develop an objective cognitive impairment.

Animal-assisted activity and emotional status of patients with Alzheimer's disease in day care.

BACKGROUND: Preliminary studies suggest beneficial effects of animal-assisted activities (AAA) on behavioral and psychological symptoms of dementia (BPSD), but data are inconsistent. This study aimed to assess the effect of AAA with dogs on cognition, BPSD, emotional status and motor activity in severe Alzheimer's disease (AD). METHODS: Ten patients attending an Alzheimer Day Care Center (ADCC) participated in a repeated measures study, which included: two weeks' pre-intervention, three weeks' control activity with plush dogs (CA), and three weeks' AAA. Cognitive function (Severe Impairment Battery), mood (Cornell Scale for Depression in Dementia; CSDD), BPSD (Neuropsychiatric Inventory; NPI) and agitation (Cohen-Mansfield Agitation Inventory; CMAI) were assessed at baseline and after each period. Observed Emotion Rating Scale (OERS) for emotional status, Agitated Behavior Mapping Instrument (ABMI) and a checklist for motor activity were completed across the study periods, both during intervention sessions and after three hours. RESULTS: Cognition and NPI were unchanged across the study. Declines in the CMAI and CSDD scores after AAA were not significant, while the NPI anxiety item score decreased in comparison with CA (CA 3.1±2.3, AAA 1.5±2.7, p = 0.04). OERS "sadness" decreased (p = 0.002), while "pleasure" (p = 0.016) and "general alertness" (p = 0.003) increased during AAA compared with CA sessions, and observed sadness remained lower after three hours (p = 0.002). Motor activity increased significantly during AAA. CONCLUSION: In this sample of severe AD patients in ADCC, AAA was associated with a decrease in anxiety and sadness and an increase in positive emotions and motor activity in comparison with a control activity.

KIBRA gene variants are associated with episodic memory performance in subjective memory complaints.

The KIBRA gene encodes a cytoplasmatic protein, a member of the signal transduction protein family, expressed mainly in the brain. Recent studies have implicated the involvement of a genetic variation in the KIBRA gene (T allele) in human memory in normal subjects and in the risk of developing Alzheimer's disease (AD). We report here the distribution of the KIBRA genetic variant and the Apolipoprotein E (ApoE) epsilon4 allele and their association with neuropsychological measures in older adults reporting problems with everyday memory (subjective memory complaints, SMC). We found that SMC subjects with the CT/TT genotype performed more poorly than those with the CC genotype on long-term memory tests. Thus, in our opinion, these data suggest that the KIBRA genotype could affect memory performance in a different way in those that complain of memory deficits compared to those that do not.

Pattern and progression of cognitive decline in Alzheimer's disease: role of premorbid intelligence and ApoE genotype.

BACKGROUND/AIMS: Because of controversial results across studies, we evaluated the predictive value of premorbid intelligence and the apolipoprotein E (ApoE) genotype on baseline and progression of cognitive performance in Alzheimer's disease (AD). METHODS: Eighty-five mild AD cases, ApoE genotyped and included in a longitudinal cliniconeuropsychological-genetic study, underwent a premorbid intelligence test and up to 11 (average 5) neuropsychological assessments. We applied linear- and logistic-regression models for cross-sectional data and mixed models for longitudinal ones. RESULTS: Higher premorbid intelligence was associated with higher global, executive and memory performance, while the ApoE epsilon 4 allele was specifically related to poorer memory performance. The premorbid intelligence-ApoE epsilon 4/epsilon 4 interaction was significant, with higher premorbid intelligence scores reducing the detrimental effect of ApoE epsilon 4 homozygosity on memory performance. Higher premorbid intelligence, but not the ApoE epsilon 4 allele, was related to faster memory deficit progression. CONCLUSION: The association of higher premorbid intelligence with better baseline cognitive performance and faster memory decline, as well as its interaction with the ApoE genotype, strengthens the role of cognitive reserve in shaping the disease's clinical expression. Our findings confirm that the epsilon 4 allele affects memory deficit at baseline but does not exert any influence on the rate of cognitive decline.

Differential impact of brain damage on the access mode to memory representations: an information theoretic approach.

Different access modes to information stored in long-term memory can lead to different distributions of errors in classification tasks. We have designed a famous faces memory classification task that allows for the extraction of a measure of metric content, an index of the relevance of semantic cues for classification performance. High levels of metric content are indicative of a relatively preferred semantic access mode, while low levels, and similar correct performance, suggest a preferential episodic access mode. Compared with normal controls, the metric content index was increased in patients with Alzheimer's disease (AD), decreased in patients with herpes simplex encephalitis, and unvaried in patients with insult in the prefrontal cortex. Moreover, the metric content index was found to correlate with a measure of the severity of dementia in patients with AD, and to track the progression of the disease. These results underline the role of the medial-temporal lobes and of the temporal cortex, respectively, for the episodic and semantic routes to memory retrieval. Moreover, they confirm the reliability of information theoretic measures for characterizing the structure of the surviving memory representations in memory-impaired patient populations.

Brain-derived neurotrophic factor, apolipoprotein E genetic variants and cognitive performance in Alzheimer's disease.

Since greater attention has been paid to the direct link of genetic variation to cognition and memory performance, apolipoprotein E (ApoE) and brain-derived neurotrophic factor (BDNF) have been the two most frequently studied genes. To investigate the effect of BDNF and ApoE polymorphisms on the cognitive profile of mild-moderate Alzheimer's disease (AD) cases, AD patients, genotyped for ApoE and BDNF polymorphisms, underwent extensive neuropsychological investigation. The effect of either ApoE epsilon4 allele and BDNF genetic variant on the neuropsychological pattern of mental impairment was examined both in terms of group differences in performance on the neuropsychological tests between carriers and non-carriers of each variant and by selecting the best predictor of cognitive performance among demographic and genetic factors by means of a multiple regression analysis. Our data confirm a specific effect caused by the presence and amount of ApoE epsilon4 allele, while they suggest that BDNF genetic variants are not a susceptibility factor to AD.

Identification of new presenilin gene mutations in early-onset familial Alzheimer disease.

BACKGROUND: Mutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes, and more rarely in beta-amyloid precursor protein (betaAPP), underlie the pathogenesis of most cases of familial Alzheimer disease (FAD). OBJECTIVE: To screen the entire coding region of the PS1 and PS2 genes and exons 16 and 17 of the betaAPP to find pathogenetic mutations in FAD. Patients Patients with FAD were consecutively enrolled from among the outpatients from the neurology departments at the Universities of Florence and Parma and the Santa Maria Nuova Hospital in Reggio Emilia, Italy. DESIGN AND METHODS: Polymerase chain reaction-single-strand conformation polymorphism and DNA se-quencing were used to investigate the affected members of families with FAD. RESULTS: We identified a family carrying a novel Ser130Leu mutation in the PS2 gene. Moreover, we found 2 novel PS1 mutations: Cys92Ser in exon 4 in 2 unrelated families and Leu174Met in exon 6 in the PS1 gene. We also found a fourth Italian family with the betaAPP Val717Ile mutation. CONCLUSIONS: One novel PS2 mutation associated with highly penetrant but variable age at onset (35-85 years) and 2 novel PS1 missense mutations associated with early-onset Alzheimer disease at age 49 to 54 years have been identified in Italian families. Screening for new mutations in presenilin and betaAPP genes was beneficial in characterizing gene function in FAD.

Agnosia for global patterns: When the cross-talk between grouping and visual selective attention failS.

We present a single case study of a 72-year-old mild AD patient, MC, with a highly specific deficit in deriving the global pattern of visual stimuli, in the absence of visuospatial neglect. MC shows a specific difficulty in segregating overlapping figures, in object decision, and in all neuropsychological tasks requiring perception of a global structure from local cues, such as the Street Completion Test and the perception of illusory contours and of the global level of hierarchical stimuli. The detailed neuropsychological assessment prompted a psychophysical experiment aiming to quantify the limits of perceptual grouping in MC. We measured the thresholds of integration for a closed chain of Gabor Patches as a function of background noise using stimuli with different values of the distance between the local elements. When compared to normal controls, the patient displays a statistically significant drop of performance for stimuli with the larger interelement distance. The data are interpreted in the context of the "association field" theory (Field, Hayes, & Hess, 1993). As MC presents with a marked atrophy of the right temporoparietal junction, we interpret our data as providing further evidence of a neuromodulatory role of the right temporoparietal junction over the occipital cortices, in line with recent functional evidence (Fink et al., 1997a). The study also highlights the benefits of complementing classical neuropsychological investigations with more quantitative psychophysical procedures.

Neutrophils CD11b and fibroblasts PGE(2) are elevated in Alzheimer's disease.

To evaluate whether inflammation-like mechanisms present in the brain of Alzheimer's disease (AD) patients are reflected in the periphery, the expression of CD11b in peripheral blood neutrophils and the expression and activity of inflammatory markers in cultured skin fibroblasts were examined. We found significantly higher levels of CD11b in neutrophils from sporadic AD patients than in controls and this elevation was positively correlated with disease severity and progression rate of mental decline. Cultured skin fibroblasts from familial (FAD) and sporadic AD patients and from controls were immunopositive for both isoforms of cyclooxygenase with no differences between groups. In unstimulated culture, the production of prostaglandin-E2 in the medium was significantly higher in fibroblasts from sporadic AD and FAD patients than in controls, and this elevation was reverted by the addition of 25 microM of ibuprofen. Our findings provide further evidence of the presence of inflammatory and immuno-related markers in the periphery of AD patients and support those studies indicating the beneficial effects of anti-inflammatory therapy in AD.