Neuropsychiatric symptoms and white matter hyperintensities in older adults without dementia.

OBJECTIVE: We aimed to examine associations between neuropsychiatric symptoms (NPS) and white matter hyperintensities (WMH) status in older adults without dementia under the hypothesis that WMH increased the odds of having NPS. DESIGN: Longitudinal analysis of data acquired from the National Alzheimer's Coordinating Center Uniform Data Set. SETTINGS: Data were derived from 46 National Institute on Aging - funded Alzheimer's Disease Research Centers. PARTICIPANTS: NACC participants aged ≥50 years with available data on WMH severity with a diagnosis of mild cognitive impairment (MCI) or who were cognitively unimpaired (CU) were studied. Among 4617 CU participants, 376 had moderate and 54 extensive WMH. Among 3170 participants with MCI, 471 had moderate and 88 had extensive WMH. MEASUREMENTS: Using Cardiovascular Health Study (CHS) scores, WMH were coded as no to mild (CHS score: 0-4), moderate (score: 5-6) or extensive (score: 7-8). NPS were quantified on the Neuropsychiatric Inventory Questionnaire. Binary logistic regression models estimated the odds of reporting each of 12 NPS by WMH status separately for individuals with MCI or who were CU. RESULTS: Compared to CU individuals with no to mild WMH, the odds of having elation [9.87, (2.63-37.10)], disinhibition [4.42, (1.28-15.32)], agitation [3.51, (1.29-9.54)] or anxiety [2.74, (1.28-5.88)] were higher for the extensive WMH group, whereas the odds of having disinhibition were higher for the moderate WMH group [1.94, (1.05-3.61)]. In the MCI group, he odds of NPS did not vary by WMH status. CONCLUSIONS: Extensive WMH were associated with higher odds of NPS in CU older adults but not in those with MCI.

Analysis of ADORA2A rs5760423 and CYP1A2 rs762551 Genetic Variants in Patients with Alzheimer's Disease.

Various studies have been conducted, exploring the genetic susceptibility of Alzheimer's disease (AD). Adenosine receptor subtype A2a (ADORA2A) and cytochrome P450 1A2 (CYP1A2) are implicated in pathways such as oxidative stress and caffeine metabolism, which are associated with AD. The aim of this study was to explore for any potential association between the ADORA2A rs5760423 and the CYP1A2 rs762551 genetic variants and AD. A case-control study was performed with a total of 654 subjects (327 healthy controls and 327 patients with AD). Five genetic models were assumed. We also examined the allele-allele combination of both variants. The value of 0.05 was considered as the statistical significance threshold. A statistically significant association was found between ADORA2A rs5760423 and AD, as the "T" allele was associated with increased AD risk in recessive (OR = 1.51 (1.03-2.21)) and log-additive (OR = 1.30 (1.04-1.62)) genetic modes. In the codominant model, the TT genotype was more prevalent compared to the GG genotype (OR = 1.71 (1.09-2.66)). The statistical significance was maintained after adjustment for sex. No association between CYP1A2 rs762551 or allele-allele combination and AD was detected. We provide preliminary indication for a possible association between the ADORA2A rs5760423 genetic polymorphism and AD.

Qualitative Verbal Fluency Components as Prognostic Factors for Developing Alzheimer's Dementia and Mild Cognitive Impairment: Results from the Population-Based HELIAD Cohort.

Background and Objectives: The aim of the present study was to investigate the prognostic value of the qualitative components of verbal fluency (clustering, switching, intrusions, and perseverations) on the development of mild cognitive impairment (MCI) and dementia. Materials and Methods: Participants were drawn from the multidisciplinary, population-based, prospective HELIAD (Hellenic Longitudinal Investigation of Aging and Diet) cohort. Two participant sets were separately analysed: those with normal cognition and MCI at baseline. Verbal fluency was assessed via one category and one letter fluency task. Separate Cox proportional hazards regressions adjusted for important sociodemographic parameters were performed for each qualitative semantic and phonemic verbal fluency component. Results: There were 955 cognitively normal (CN), older (72.9 years ±4.9), predominantly female (~60%) individuals with available follow-up assessments after a mean of 3.09 years (±0.83). Among them, 34 developed dementia at follow-up (29 of whom progressed to Alzheimer's dementia (AD)), 160 developed MCI, and 761 remained CN. Each additional perseveration on the semantic condition increased the risk of developing all-cause dementia and AD by 52% and 55%, respectively. Of note, participants with two or more perseverations on the semantic task presented a much more prominent risk for incident dementia compared to those with one or no perseverations. Among the remaining qualitative indices, none were associated with the hazard of developing all-cause dementia, AD, and MCI at follow-up. Conclusions: Perseverations on the semantic fluency condition were related to an increased risk of incident all-cause dementia or AD in older, CN individuals.

The Nitric Oxide (NO) Donor Sodium Nitroprusside (SNP) and Its Potential for the Schizophrenia Therapy: Lights and Shadows.

Schizophrenia is a severe psychiatric disorder affecting up to 1% of the worldwide population. Available therapy presents different limits comprising lack of efficiency in attenuating negative symptoms and cognitive deficits, typical features of schizophrenia and severe side effects. There is pressing requirement, therefore, to develop novel neuroleptics with higher efficacy and safety. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, appears to be implicated in the pathogenesis of schizophrenia. In particular, underproduction of this gaseous molecule is associated to this mental disease. The latter suggests that increment of nitrergic activity might be of utility for the medication of schizophrenia. Based on the above, molecules able to enhance NO production, as are NO donors, might represent a class of compounds candidates. Sodium nitroprusside (SNP) is a NO donor and is proposed as a promising novel compound for the treatment of schizophrenia. In the present review, we intended to critically assess advances in research of SNP for the therapy of schizophrenia and discuss its potential superiority over currently used neuroleptics.

Motor signs and incident dementia with Lewy bodies in older adults with mild cognitive impairment.

BACKGROUND: Motor signs may herald incident dementia and allow the earlier detection of high-risk individuals and the timely implementation of preventive interventions. The current study was performed to investigate the prognostic properties of motor signs with respect to incident dementia with Lewy bodies (DLB) in older adults with mild cognitive impairment (MCI). Emphasis was placed on sex differences. The specificity of these associations was explored. METHODS: We analyzed data from the National Alzheimer's Coordinating Center Uniform Data Set. Participants 55 + years old with a diagnosis of MCI were included in the analysis. Those with Parkinson's disease (PD) or other parkinsonian disorders at baseline and those with PD dementia at follow-up were excluded. UPDRS III was used to assess the presence or absence of motor signs in nine domains: hypophonia; masked facies; resting tremor; action/postural tremor; rigidity; bradykinesia; impaired chair rise; impaired posture/gait; postural instability. Αdjusted Cox proportional hazards models featuring sex by motor sign interactions were estimated. RESULTS: Throughout the average follow-up of 3.7 ± 3.1 years, among 4623 individuals with MCI, 2211 progressed to dementia (66 of whom converted to DLB). Masked facies [HR = 4.21 (1.74-10.18)], resting tremor [HR = 4.71 (1.44-15.40)], and bradykinesia [HR = 3.43 (1.82-6.45)] exclusively increased the risk of DLB. The HR of DLB was approximately 15 times greater in women compared to men with masked facies. Impaired posture-gait (approximately 10 times) and resting tremor (approximately 8.5 times) exhibited a similar trend (prominent risk-conferring properties in women compared to men) but failed to achieve statistical significance. Rigidity and hypophonia elevated the risk of other dementia entities, as well. The remaining motor features were not related to incident dementia of any type. CONCLUSIONS: Specific motor signs may herald DLB among individuals with MCI. Different associations may exist between masked facies, impaired posture-gait, resting tremor, and incident DLB in men versus women.

The impact of genetic factors on the response to migraine therapy.

Migraine is a multidimensional disease affecting a large portion of the human population presenting with a variety of symptoms. In the era of personalized medicine, successful migraine treatment presents a challenge, as several studies have shown the impact of a patient's genetic profile on therapy response. However, with the emergence of contemporary treatment options, there is promise for improved outcomes. A literature search was conducted in PubMed and Scopus, in order to obtain studies investigating the impact of genetic factors on migraine therapy outcome. Overall, 23 studies were included in the current review, exhibiting diversity in the treatments used and the genetic variants investigated. Divergent genes were assessed for each category of migraine treatment. Several genetic factors were identified to contribute to the heterogeneous response to treatment. SNPs related to pharmacodynamic receptors, pharmacogenetics and migraine susceptibility loci were the most investigated variants, revealing some interesting significant results. To date, various associations have been recorded correlating the impact of genetic factors on migraine treatment responses. More extensive research needs to take place with the aim of shedding light on the labyrinthine effects of genetic variations on migraine treatment, and, consequently, these findings can promptly affect migraine treatment and improve migraine patients' life quality in the vision of precise medicine.

Computer-Based Cognitive Training vs. Paper-and-Pencil Training for Language and Cognitive Deficits in Greek Patients with Mild Alzheimer's Disease: A Preliminary Study.

The purpose of the present study was to explore whether Computer-Based Cognitive Training (C-BCT) versus Paper-Pencil Cognitive Training (P-PCT) is more beneficial in improving cognitive and language deficits in Greek patients living with Alzheimer's disease (pwAD). Twenty pwAD were assigned to two groups: (a) the C-BCT group, receiving a computer-based cognitive training program using the RehaCom software, and (b) the P-PCT group, which received cognitive training using paper and pencil. The cognitive training programs lasted 15 weeks and were administered twice a week for approximately one hour per session. The analyses of each group's baseline versus endpoint performance demonstrated that the P-PCT group improved on delayed memory, verbal fluency, attention, processing speed, executive function, general cognitive ability, and activities of daily living. In contrast, the C-BCT group improved on memory (delayed and working), naming, and processing speed. Comparisons between the two groups (C-BCT vs. P-PCT) revealed that both methods had significant effects on patients' cognition, with the P-PCT method transferring the primary cognitive benefits to real-life activities. Our findings indicate that both methods are beneficial in attenuating cognitive and language deficits in pwAD. The need for large-scale neurobehavioral interventions to further clarify this issue, however, remains a priority.

The novel dehydroepiandrosterone derivative BNN27 counteracts the impairing effects of anesthetic ketamine on rats' non-spatial and spatial recognition memory.

Conspicuous experimental evidence indicates that anesthetic doses of the non-competitive NMDA receptor antagonist ketamine disrupt memory abilities in rodents. BNN27 is a synthetic analogue of dehydroepiandrosterone (DHEA) with potent antioxidant properties and its involvement in cognition has recently been shown. It is not yet clarified whether BNN27 can attenuate the cognition deficits induced by anesthetic ketamine. The present study was designed to elucidate this issue in the rat. For this purpose, the object recognition and the object location tests which are behavioral procedures evaluating non-spatial and spatial recognition memory respectively in rodents were used. The effects of compounds on motility were also tested utilizing a motor activity cage. Post-training administration of BNN27 (3 and 6 mg/kg, intraperitoneally) counteracted anesthetic ketamine (100 mg/kg, intraperitoneally)-induced non-spatial and spatial recognition memory deficits. Further, these effects cannot be attributed to changes to locomotor activity. Our findings clearly show the protective role of BNN27, on recognition memory impairment induced by anesthetic ketamine, indicating a functional interaction following co-administration of synthetic microneurotrophins and ketamine.

Cognitive Rehabilitation in Schizophrenia-Associated Cognitive Impairment: A Review.

Patients suffering from schizophrenia often experience cognitive disturbances. Cognitive rehabilitation-computerized or non-computerized-is widely known as an alternative way to enhance cognitive functioning in patients with schizophrenia. The aim of the present review was to examine the role of cognitive rehabilitation (both computerized and non-computerized) for the alleviation of cognitive impairment in schizophrenia patients. Fourteen relative studies were examined and included in the present review. The results revealed that both computerized and non-computerized cognitive rehabilitation could enhance cognitive functioning and more specifically memory, attention, executive functioning, processing speed and in a few cases, even non-cognitive impairments, such as other schizophrenia symptoms. The present results support the efficacy of cognitive rehabilitation in schizophrenia patients, regardless of whether it is computerized or non-computerized. As the randomized control trials (RCTs) are limited in number, there is urgent need for more RCTs and longitudinal studies combining different kinds of interventions, as well as systematic reviews and meta-analyses, in order to further investigate and confirm the current results.

The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts cognitive deficits induced by the D1/D2 dopaminergic receptor agonist apomorphine in rats.

RATIONALE: Schizophrenia is a devastating mental disease that affects nearly 1% of the population worldwide. It is well documented that the dopaminergic (DAergic) system is compromised in schizophrenia. It is of note that the mixed dopamine (DA) D1/D2 receptor agonist apomorphine induces schizophrenia-like symptoms in rodents, including disruption of memory abilities. Neuroactive steroids, comprising dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS), were shown to affect brain DAergic system and to be involved in schizophrenia. BNN27 is a novel DHEA derivative, which is devoid of steroidogenic activity. It has recently been reported that BNN27 counteracted schizophrenia-like behavioural deficits produced by glutamate hypofunction in rats. OBJECTIVES: The aim of the present study was to investigate the ability of BNN27 to attenuate non-spatial, spatial recognition and discrete memory deficits induced by apomorphine in rats. METHODS: To this end, the object recognition task (ORT), the object location task (OLT) and the step-through passive avoidance test (STPAT) were used. RESULTS: BNN27 (3 and 6 mg/kg, i.p.) attenuated apomorphine (0.5 mg/kg, i.p.)-induced non-spatial, spatial recognition and discrete memory deficits. Interestingly, the effects of compounds on memory cannot be ascribed to changes in locomotor activity. CONCLUSIONS: Our findings suggest that BNN27 is effective to DA dysfunction caused by apomorphine, attenuating cognitive impairments induced by this D1/D2 receptor agonist in rats. Additionally, our findings illustrate a functional interaction between BNN27 and the DAergic system that may be of relevance for schizophrenia-like behavioural symptoms.

The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts behavioural deficits induced by the NMDA receptor antagonist ketamine in rats.

Consistent experimental evidence supports an important role of the glutamatergic system in the etiopathogenesis of schizophrenia. Numerous studies propose that blockade of the NMDA receptor by its antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Neuroactive steroids, including dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were shown to affect brain glutamatergic system and to be implicated in schizophrenia. BNN27 is a novel DHEA derivative, which is devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently evidenced. The aim of the present study was to investigate the ability of BNN27 to counteract schizophrenia-like behavioural deficits produced by ketamine in rats. BNN27's ability to attenuate hypermotility, stereotypies and ataxia induced by ketamine were evaluated using a motor activity cage. To assess the efficacy of BNN27 to reverse non-spatial and spatial recognition memory deficits caused by ketamine, the object recognition task and the object location task were used. Finally, the social interaction test was utilized in order to examine the effects of BNN27 on ketamine-induced social withdrawal. BNN27 (3 and 6 mg/kg, i.p.) attenuated ketamine (10 mg/kg, i.p.)-induced ataxia and to some extent also hypermotility. BNN27 (3-6 mg/kg, i.p.) counteracted ketamine (3 mg/kg, i.p.)-induced non-spatial and spatial recognition memory deficits. Further, BNN27 (6 mg/kg, i.p.) reduced the ketamine (8 mg/kg, i.p.)-induced social isolation. Our findings show that BNN27 is sensitive to glutamate hypofunction produced by ketamine since it reduced schizophrenia-like behavioural deficits induced by this NMDA receptor antagonist in rats.