Significance of the anterior cingulate cortex in neurogenesis plasticity: Connections, functions, and disorders across postnatal and adult stages.

The anterior cingulate cortex (ACC) is a complex and continually evolving brain region that remains a primary focus of research due to its multifaceted functions. Various studies and analyses have significantly advanced our understanding of how the ACC participates in a wide spectrum of memory and cognitive processes. However, despite its strong connections to brain areas associated with hippocampal and olfactory neurogenesis, the functions of the ACC in regulating postnatal and adult neurogenesis in these regions are still insufficiently explored. Investigating the intricate involvement of the ACC in neurogenesis could enhance our comprehension of essential aspects of brain plasticity. This involvement stems from its complex circuitry with other relevant brain regions, thereby exerting both direct and indirect impacts on the neurogenesis process. This review sheds light on the promising significance of the ACC in orchestrating postnatal and adult neurogenesis in conditions related to memory, cognitive behavior, and associated disorders.

Differential Effects of Neonatal Ventral Hippocampus Lesion on Behavior and Corticolimbic Plasticity in Wistar-Kyoto and Spontaneously Hypertensive Rats.

Dysfunction of the corticolimbic system, particularly at the dendritic spine level, is a recognized core mechanism in neurodevelopmental disorders such as schizophrenia. Neonatal ventral hippocampus lesion (NVHL) in Sprague-Dawley rats induces both a schizophrenia-related behavioral phenotype and dendritic spine pathology (reduced total number and mature spines) in corticolimbic areas, which is mitigated by antipsychotics. However, there is limited information on the impact of rat strain on NVHL outcomes and antipsychotic effects. We compared the behavioral performance in the open field, novel object recognition (NORT), and social interaction tests, as well as structural neuroplasticity with the Golgi-Cox stain in Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) male rats with and without NVHL. Additionally, we explored the effect of the atypical antipsychotic risperidone (RISP). WKY rats with NVHL displayed motor hyperactivity without impairments in memory and social behavior, accompanied by dendritic spine pathology in the neurons of the prefrontal cortex (PFC) layer 3 and basolateral amygdala. RISP treatment reduced motor activity and had subtle and selective effects on the neuroplasticity alterations. In SH rats, NVHL increased the time spent in the border area during the open field test, impaired the short-term performance in NORT, and reduced social interaction time, deficits that were corrected after RISP administration. The NVHL caused dendritic spine pathology in the PFC layers 3 and 5 of SH rats, which RISP treatment ameliorated. Our results support the utility of the NVHL model for exploring neuroplasticity mechanisms in schizophrenia and understanding pharmacotherapy.

Preschoolers retain more details from event sequences 1 week following an in-group demonstration.

Previous research highlights that the learning processes of preschool-aged children are influenced by the cultural group membership of the information sources. As of yet, however, no study has aimed to explore the influence of cultural group membership on the long-term retention of novel information. In the current study, 4-year-old children observed three event sequences that were demonstrated by either an adult speaking their native language or a foreign language speaker. In Experiment 1, children (N = 56) were allowed to imitate the events immediately. Results showed that the average number of accurately reproduced details (native = 3.26; foreign = 3.11) and the order of event elements (native = 1.69; foreign = 1.49) did not significantly differ in the two conditions. In Experiment 2, children (N = 56) were allowed to imitate only following a 1-week delay. In this case, children retained more details (native = 2.6; foreign = 2.2) and reproduced the order in the event sequences more accurately (native = 1.18; foreign = 0.87) following a native demonstration. The behavior of children in all conditions differed from a baseline group without any instruction (n = 15). These findings show that preschoolers retain more information in the long term when it was demonstrated to them by a member of their own culture. Importantly, they also learn from people belonging to different cultures-as evidenced by both the lack of difference in Experiment 1 and the difference between the out-group condition of Experiment 2 and the baseline.

Grape seed extract protects rat offspring hippocampus from the silicon dioxide nanoparticles' neurotoxicity.

Silicon dioxide nanoparticles (SiO2-NPs) can be found in many products, such as composites, paints, ceramics, consumer products, and food additives. We recently demonstrated that via breastfeeding, SiO2-NPs transfer to the offspring's brain, interfering negatively with hippocampus development. In this work, we evaluated the protective effect of grape seed extract (GSE) against the adverse effects of SiO2-NPs. After delivery, animals were administered 25 mg/kg SiO2-NPs with/without GSE (300 mg/kg) for 20 days (from 2nd to 21st days post-delivery) by gavage. SiO2-NPs increased malondialdehyde concentration and decreased antioxidant activity in the offspring's hippocampi. The mean number of dark neurons (DNs) was significantly higher in the hippocampi of the SiO2-NPs group, whereas the mean number of DCX + cells was significantly lower than in the control group. The offspring in the SiO2-NPs groups had a weak cognitive performance in adulthood. Interestingly, these adverse effects of SiO2-NPs were alleviated in the GSE-treated groups. Therefore, GSE can attenuate the damaging effects of maternal exposure to SiO2-NPs during lactation.

Long-term food supplementation with sweet basil (Ocimum basilicum L.) prevents age-associated cognitive decline in female mice.

Background: Mild cognitive decline, a common issue in aging, affects memory, learning, and attention. Nutrition can influence cognition, and research indicates that Ocimum sp. (holy basil and sweet basil) leaf extracts may enhance cognition in rodents and humans. However, these studies do not address whether these benefits extend to fresh or dry leaves consumed in typical human diets, along with physiological aging. Aim: To investigate the effects of sweet basil supplementation on cognition in mature and aged female mice. Methods: Female C57bl mice were divided into four groups: 8-month-old mature adults and 18-month-old aged adults, each receiving either a control or supplemented diet. The supplemented diet included a mix of standard chow and fresh basil leaves, administered for 2-8 months. Cognitive and behavioral assessments were conducted using the novel object recognition (NOR), Morris water maze (MWM), and elevated plus maze (EPM) tasks, focusing on memory, learning, and anxiety. Results: No cognitive improvement was observed in mature mice. However, aged mice receiving long-term basil supplementation showed enhanced discrimination in NOR and stayed closer to the absent platform in MWM compared to nonsupplemented controls. While aging mice exhibited reduced anxiety-like behavior in EPM, basil supplementation prevented this reduction. Conclusion: Basil supplementation appears beneficial in elderly mice, potentially preventing age-related cognitive decline and behavioral changes. These findings support the benefits of basil consumption in cognition and underscore its potential role in promoting healthy aging. Incorporating basil into the diet at a younger age may preserve memory and mitigate behavioral changes as individuals age.

Geographic variability in limited English proficiency: A cross-cultural study of cognitive profiles.

OBJECTIVE: This study was designed to evaluate the effect of limited English proficiency (LEP) on neurocognitive profiles. METHOD: Romanian (LEP-RO; n = 59) and Arabic (LEP-AR; n = 30) native speakers were compared to Canadian native speakers of English (NSE; n = 24) on a strategically selected battery of neuropsychological tests. RESULTS: As predicted, participants with LEP demonstrated significantly lower performance on tests with high verbal mediation relative to US norms and the NSE sample (large effects). In contrast, several tests with low verbal mediation were robust to LEP. However, clinically relevant deviations from this general pattern were observed. The level of English proficiency varied significantly within the LEP-RO and was associated with a predictable performance pattern on tests with high verbal mediation. CONCLUSIONS: The heterogeneity in cognitive profiles among individuals with LEP challenges the notion that LEP status is a unitary construct. The level of verbal mediation is an imperfect predictor of the performance of LEP examinees during neuropsychological testing. Several commonly used measures were identified that are robust to the deleterious effects of LEP. Administering tests in the examinee's native language may not be the optimal solution to contain the confounding effect of LEP in cognitive evaluations.

Protection of Mice from Controlled Cortical Impact Injury by Food Additive Glyceryl Tribenzoate.

Despite intense investigations, no effective therapy is available to halt the pathogenesis of traumatic brain injury (TBI), a major health concern, which sometimes leads to long-term neurological disability, especially in war veterans and young adults. This study highlights the use of glyceryl tribenzoate (GTB), a flavoring ingredient, in ameliorating the disease process of controlled cortical impact (CCI)-induced TBI in mice. Oral administration of GTB decreased the activation of microglia and astrocytes to inhibit the expression of inducible nitric oxide synthase (iNOS) in hippocampus and cortex of TBI mice. Accordingly, GTB treatment protected and/or restored synaptic maturation in the hippocampus of TBI mice as revealed by the status of PSD-95, NR-2A and GluR1. Furthermore, oral GTB also reduced the size of lesion cavity in the brain of TBI mice. Finally, GTB treatment improved locomotor functions and protected spatial learning and memory in TBI mice. These results outline a novel neuroprotective property of GTB which may be beneficial in treatment of TBI.

Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis.

Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70-84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsychological investigations can offer important insights into the nature, origin and pathophysiology of treatment-resistant schizophrenia (TRS), but methodological limitations in a still emergent field of research have obscured the neuropsychological discriminability of TRS. We report on the first systematic review and meta-analysis to investigate neuropsychological differences between TRS patients and treatment-responsive controls across 17 published studies (1864 participants). Five meta-analyses were performed in relation to (1) executive function, (2) general cognitive function, (3) attention, working memory and processing speed, (4) verbal memory and learning, and (5) visual-spatial memory and learning. Small-to-moderate effect sizes emerged for all domains. Similarly to previous comparisons between unselected, drug-naïve and first-episode schizophrenia samples v. healthy controls in the literature, the largest effect size was observed in verbal memory and learning [dl = -0.53; 95% confidence interval (CI) -0.29 to -0.76; z = 4.42; p < 0.001]. A sub-analysis of language-related functions, extracted from across the primary domains, yielded a comparable effect size (dl = -0.53, 95% CI -0.82 to -0.23; z = 3.45; p < 0.001). Manipulating our sampling strategy to include or exclude samples selected for clozapine response did not affect the pattern of findings. Our findings are discussed in relation to possible aetiological contributions to TRS.

Validation and Normative Data of the Spanish Version of the Face Name Associative Memory Exam (S-FNAME).

OBJECTIVE: The relevance of the episodic memory in the prediction of brain aging is well known. The Face Name Associative Memory Exam (FNAME) is a valued associative memory measure related to Alzheimer's disease (AD) biomarkers, such as amyloid-ß deposition preclinical AD individuals. Previous validation of the Spanish version of the FNAME test (S-FNAME) provided normative data and psychometric characteristics. The study was limited to subjects attending a memory clinic and included a reduced sample with gender inequality distribution. The purpose of this study was to assess S-FNAME psychometric properties and provide normative data in a larger independent sample of cognitively healthy individuals. METHOD: S-FNAME was administered to 511 cognitively healthy volunteers (242 women, aged 41-65 years) participating in the Barcelona Brain Health Initiative cohort study. RESULTS: Factor analysis supported construct validity revealing two underlying components: face-name and face-occupation and explaining 95.34% of the total variance, with satisfactory goodness of fit. Correlations between S-FNAME and Rey Auditory-Verbal Learning Test were statistically significant and confirmed its convergent validity. We also found weak correlations with non-memory tests supporting divergent validity. Women showed better scores, and S-FNAME was positively correlated with education and negatively with age. Finally, we generated normative data. CONCLUSIONS: The S-FNAME test exhibits good psychometric properties, consistent with previous findings, resulting in a valid and reliable tool to assess episodic memory in cognitively healthy middle-aged adults. It is a promising test for the early detection of subtle memory dysfunction associated with abnormal brain aging.

Grape seed extract effects on hippocampal neurogenesis, synaptogenesis and dark neurons production in old mice. Can this extract improve learning and memory in aged animals?

BACKGROUND: During the elderly, hippocampal neurogenesis and synaptogenesis reduce and dark neurons (DNs) increase, leading to cognitive impairment. It is believed that natural products can protect the neural cells and system by protecting from damages or promoting regeneration. Therefore, the effects of grape seed extract (GSE) on the hippocampus of aged mice were investigated in this study. METHODS: twelve old mice were divided into two groups of control and GSE. Animals in the GSE group received 300 mg/kg of GSE for eight weeks via gavage. At the end of treatment, cognition performance was evaluated by Morris water maze (MWM) and passive avoidance tests. Hippocampal neurogenesis, synaptogenesis and DNs production were evaluated with immunohistochemistry and histological evaluations on 5-micron coronal tissue sections. RESULTS: The hippocampal mean number of double cortin positive cells (DCX+) per unit area, as well as synaptophysin expression in the GSE group, were significantly higher than the control group (p < 0.01). The frequency of DNs in the GSE group was lower than the control group (p < 0.05). Behavioral tests showed that GSE improves memory and learning performance. CONCLUSION: Consuming GSE in the elderly can potentially alleviate the age-related reduction of hippocampal neurogenesis and synaptogenesis. It is also able to decrease hippocampal DNs production and increase memory and learning.

The Influence of CB2-Receptor Ligands on the Memory-Related Responses in Connection with Cholinergic Pathways in Mice in the Passive Avoidance Test.

Background: Dysfunction of the cholinergic system is associated with the development of Alzheimer's disease (AD). One of the new possible strategies for the pharmacological modulation of memory-related problems typical of AD, is connected with the endocannabinoid system (ECS) and the cannabinoid (CB: CB1 and CB2) receptors. Methods: The aim of the study was to determine the influence of the selective CB2 receptor ligands: agonist (JWH 133) and antagonist (AM 630) on different stages of memory and learning in mice, in the context of their interaction with cholinergic pathways. To assess and understand the memory-related effects in mice we used the passive avoidance (PA) test. Results: We revealed that co-administration of non-effective dose of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the non-effective dose of cholinergic receptor agonist - nicotine (0.05 mg/kg) enhanced cognition in the PA test in mice; however, an acute injection of JWH 133 (0.25 mg/kg) or AM 630 (0.25 mg/kg) had no influence on memory enhancement induced by the effective dose of nicotine (0.1 mg/kg). Co-administration of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the effective dose of the cholinergic receptor antagonist scopolamine (1 mg/kg) attenuated the scopolamine-induced memory impairment in the PA test in mice. Conclusion: Our experiments have shown that CB2 receptors participate in the modulation of memory-related responses, especially those in which cholinergic pathways are implicated.

Maqui berry (Aristotelia chilensis) extract improves memory and decreases oxidative stress in male rat brain exposed to ozone.

Introduction: Prolonged ozone exposure can produce a state of oxidative stress, which in turn causes alterations in the dynamics of the brain and affects memory and learning. Moreover, different investigations have shown that high flavonoid content berries show a great antioxidant activity. The relationship between the protective effect of the maqui berry extract and its antioxidant properties in the brain has not been studied in depth. Objectives: The present study evaluated whether the protection exerted by the aqueous extract of maqui berry in brain regions associated with cognitive performance is due to its antioxidant capacity. Methods: Sprague Dawley rats were exposed to 0.25 ppm ozone and administered with maqui berry extracts. At the end of the treatments, spatial learning and short- and long-term memory were evaluated, as well as oxidative stress markers. Results: The administration of 50 and 100 mg/kg of the aqueous extract of maqui berry was effective in preventing the cognitive deficit caused by chronic exposure to ozone. The antioxidant effect of the administration of maqui berry was analyzed in the prefrontal cortex, hippocampus, and amygdala. Oxidative stress markers levels decreased and the enzymatic activity of superoxide dismutase diminished in animals exposed to ozone treated with the 50 mg/kg dose of maqui berry. Discussion: These results show a relationship between protection at the cognitive level and a decrease in oxidative stress markers, which suggests that the prevention of cognitive damage is due to the antioxidant activity of the maqui berry.

Aspirin binds to PPARα to stimulate hippocampal plasticity and protect memory.

Despite its long history, until now, no receptor has been identified for aspirin, one of the most widely used medicines worldwide. Here we report that peroxisome proliferator-activated receptor alpha (PPARα), a nuclear hormone receptor involved in fatty acid metabolism, serves as a receptor of aspirin. Detailed proteomic analyses including cheminformatics, thermal shift assays, and TR-FRET revealed that aspirin, but not other structural homologs, acts as a PPARα ligand through direct binding at the Tyr314 residue of the PPARα ligand-binding domain. On binding to PPARα, aspirin stimulated hippocampal plasticity via transcriptional activation of cAMP response element-binding protein (CREB). Finally, hippocampus-dependent behavioral analyses, calcium influx assays in hippocampal slices and quantification of dendritic spines demonstrated that low-dose aspirin treatment improved hippocampal plasticity and memory in FAD5X mice, but not in FAD5X/Ppara-null mice. These findings highlight a property of aspirin: stimulating hippocampal plasticity via direct interaction with PPARα.

Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Improves Cognitive Functions in Mice after Controlled Cortical Impact Injury.

Traumatic brain injury (TBI) is a major health concern, sometimes leading to long-term neurological disability, especially in children, young adults and war veterans. Although research investigators and clinicians have applied different treatment strategies or neurosurgical procedures to solve this health issue, we are still in need of an effective therapy to halt the pathogenesis of brain injury. Earlier, we reported that sodium benzoate (NaB), a metabolite of cinnamon and a Food and Drug Administration-approved drug against urea cycle disorders and glycine encephalopathy, protects neurons in animal models of Parkinson's disease and Alzheimer's disease. This study was undertaken to examine the therapeutic efficacy of NaB in a controlled cortical impact (CCI)-induced preclinical mouse model of TBI. Oral treatment with NaB, but not sodium formate (NaFO), was found to decrease the activation of microglia and astrocytes and to inhibit the expression of inducible nitric oxide synthase (iNOS) in the hippocampus and cortex of CCI-insulted mice. Further, administration of NaB also reduced the vascular damage and decreased the size of the lesion cavity in the brain of CCI-induced mice. Importantly, NaB-treated mice showed significant improvements in memory and locomotor functions as well as displaying a substantial reduction in depression-like behaviors. These results delineate a novel neuroprotective property of NaB, highlighting its possible therapeutic importance in TBI.

Effect of Berberine Isolated from Barberry Species by Centrifugal Partition Chromatography on Memory and the Expression of Parvalbumin in the Mouse Hippocampus Proper.

Neurodegenerative diseases associated with memory disturbances are important health issues occurring due to a prolonged life span. This article presents the results of a study targeting the emergence of a drug candidate with antiamnesic properties. The effect of berberine (BBR), an isoquinoline alkaloid isolated from the overground parts of Berberis sibirica Pall., on memory and expression of parvalbumin in the mouse hippocampus proper were determined. High-purity BBR was isolated by centrifugal partition chromatography from a methanolic extract from B. sibirica by using a methyl-tert-butyl ether and water (1:1 v/v) solvent system with 10 mmol/L of triethylamine and hydrochloric acid. In an in vivo study, we assessed the influence of the chronic administration of BBR on different stages of memory-related responses in mice. Our results indicated that the chronic administration of BBR in a higher dose (5 mg/kg) improves long-term memory acquisition in mice, as determined in the passive avoidance test. The hippocampal CA1-CA3 fields showed an increased number of parvalbumin-immunoreactive neurons (PV-IR) and nerve fibers as compared to the control. No significant changes in the dentate gyrus were observed between the groups. The HPLC-ESI-QTOF-MS/MS analysis of the biological material revealed the content of BBR as 363.4 ± 15.0 ng (4.11% of RSD) per brain, 15.06 ± 0.89 ng (5.91% of RSD) per hippocampus, and 54.45 ± 1.40 (4.05% of RSD) ng in 100 µL plasma. The study showed that BBR could be a factor influencing the expression of PV in hippocampal neurons. We speculate that BBR may modulate the level of Ca2+ in neurons and thus potentially act as a neuroprotective factor against neuronal damages.

Cannabidiol Attenuates MK-801-Induced Cognitive Symptoms of Schizophrenia in the Passive Avoidance Test in Mice.

Schizophrenia is a chronic mental disorder that disturbs feelings and behavior. The symptoms of schizophrenia fall into three categories: positive, negative, and cognitive. Cognitive symptoms are characterized by memory loss or attentional deficits, and are especially difficult to treat. Thus, there is intense research into the development of new treatments for schizophrenia-related responses. One of the possible strategies is connected with cannabidiol (CBD), a cannabinoid compound. This research focuses on the role of CBD in different stages of memory (acquisition, consolidation, retrieval) connected with fear conditioning in the passive avoidance (PA) learning task in mice, as well as in the memory impairment typical of cognitive symptoms of schizophrenia. Memory impairment was provoked by an acute injection of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (animal model of schizophrenia). Our results revealed that an acute injection of CBD (30 mg/kg; intraperitoneally (i.p.) improved all phases of long-term fear memory in the PA test in mice. Moreover, the acute injection of non-effective doses of CBD (1 or 5 mg/kg; i.p.) attenuated the memory impairment provoked by MK-801 (0.6 mg/kg; i.p.) in the consolidation and retrieval stages of fear memory, but not in the acquisition of memory. The present findings confirm that CBD has a positive influence on memory and learning processes in mice, and reveals that this cannabinoid compound is able to attenuate memory impairment connected with hypofunction of glutamate transmission in a murine model of schizophrenia.

Phenylbutyrate ameliorates prefrontal cortex, hippocampus, and nucleus accumbens neural atrophy as well as synaptophysin and GFAP stress in aging mice.

Recent reports on brain aging suggest that oxidative stress and inflammatory processes contribute to aging. Interestingly, sodium phenylbutyrate (PBA) is an inhibitor of histone deacetylase, which has anti-inflammatory properties. Several reports have suggested the effect of PBA on learning and memory processes, however there are no studies of the effect of this inhibitor of histone deacetylase on aging. Consequently, in the present study, the effect of PBA was studied in 18-month-old mice. The animals were administered PBA for 2 months after locomotor activity treatment and Morris water maze tests were performed. The Golgi-Cox staining technique and immunohistochemistry for glial fibrillary acidic protein (GFAP) and synaptophysin were performed for the morphological procedures. The administration of PBA improves learning and memory according to the Morris water maze test compared to vehicle-treated animals, which had unchanged locomotor activity. Using Golgi-Cox staining, dendritic length and the number of dendritic spines were measured in limbic regions, such as the nucleus accumbens (NAcc), prefrontal cortex (PFC) layer 3, and the CA1 of the dorsal hippocampus. In addition, PBA increased the number of dendritic spines in the PFC, NAcc, and CA1 subregions of the hippocampus with an increase in dendritic length only in the CA1 region. Moreover, PBA reduced the levels of the GFAP and increased the levels of synaptophysin in the studied regions. Thus, PBA can be a useful pharmacological tool to prevent or delay synaptic plasticity damage and cognitive impairment caused by age.

Basolateral amygdala, nicotinic cholinergic receptors, and nicotine: Pharmacological effects and addiction in animal models and humans.

The amygdala is involved in processing incoming information about rewarding stimuli and emotions that denote danger such as anxiety and fear. Bi-directional neural connections between basolateral amygdala (BLA) and brain regions such as nucleus accumbens, prefrontal cortex, hippocampus, and hindbrain regions regulate motivation, cognition, and responses to stress. Altered local regulation of BLA excitability is pivotal to the behavioral disturbances characteristic of posttraumatic stress disorder, and relapse to drug use induced by stress. Herein, we review the physiological regulation of BLA by cholinergic inputs, emphasizing the role of BLA nicotinic receptors. We review BLA-dependent effects of nicotine on cognition, motivated behaviors, and emotional states, including memory, taking and seeking drugs, and anxiety and fear in humans and animal models. The alterations in BLA activity observed in animal studies inform human behavioral and brain imaging research by enabling a more exact understanding of altered BLA function. Converging evidence indicates that cholinergic signaling from basal forebrain projections to local nicotinic receptors is an important physiological regulator of BLA and that nicotine alters BLA function. In essence, BLA is necessary for behavioral responses to stimuli that evoke anxiety and fear; reinstatement of cue-induced drug seeking; responding to second-order cues conditioned to abused drugs; reacquisition of amplified nicotine self-administration due to chronic stress during abstinence; and to promote responding for natural reward.

Immediate verbal recall and familial dementia risk: population-based study of over 4000 twins.

OBJECTIVE: To investigate the effect of familial risk for dementia on verbal learning by comparing cognitively healthy twins who had demented co-twins with cognitively healthy twins who had cognitively healthy co-twins. METHODS: 4367 twins aged ≥65 years including 1375 twin pairs (533 monozygotic (MZ), 823 dizygotic (DZ) and 19 unknown zygosity pairs) from a population-based Finnish Twin Cohort participated in a cross-sectional telephone assessment for dementia and in a single free recall trial of a 10-item word list. RESULTS: Cognitively healthy twins with demented co-twins (n=101 pairs) recalled less words than cognitively healthy twins with cognitively healthy co-twins (n=770 pairs) after adjusting for age, sex and education, B=- 0.44, 95% CI (-0.73 to -0.14), p=0.003. The effect size was similar in MZ (n=31) twins (3.88 vs 4.29 words, B=-0.41, 95% CI (-0.96 to 0.13)) and DZ (n=66) twins (3.70 vs 4.17 words, B=-0.47, 95% CI (-0.84 to -0.10)). The heritability estimate of immediate recall (IR) was 0.37, 95% CI (0.21 to 0.43). CONCLUSIONS: The results demonstrate that familial risk for dementia is reflected in the IR performance of cognitively healthy older persons. The finding of poorer IR performance in non-affected siblings compared with the general population, together with substantial heritability of IR, supports IR as a useful endophenotype for molecular genetic studies of dementia.

Multivariate Base Rates of Low Scores on Tests of Learning and Memory Among Latino Adult Populations.

OBJECTIVE: To determine the prevalence of low scores for two neuropsychological tests with five total scores that evaluate learning and memory functions. METHOD: N = 5402 healthy adults from 11 countries in Latin America and the commonwealth of Puerto Rico were administered the Rey-Osterrieth Complex Figure (ROCF) and the Hopkins Verbal Learning Test (HVLT-R). Two-thirds of the participants were women, and the average age was 53.5 ± 20.0 years. Z-scores were calculated for ROCF Copy and Memory scores and HVLT-R Total Recall, Delayed Recall, and Recognition scores, adjusting for age, age2, sex, education, and interaction variables if significant for the given country. Each Z-score was converted to a percentile for each of the five subtest scores. Each participant was categorized based on his/her number of low scoring tests in specific percentile cutoff groups (25th, 16th, 10th, 5th, and 2nd). RESULTS: Between 57.3% (El Salvador) and 64.6% (Bolivia) of the sample scored below the 25th percentile on at least one of the five scores. Between 27.1% (El Salvador) and 33.9% (Puerto Rico) scored below the 10th percentile on at least one of the five subtests. Between 5.9% (Chile, El Salvador, Peru) and 10.3% (Argentina) scored below the 2nd percentile on at least one of the five scores. CONCLUSIONS: Results are consistent with other studies that found that low scores are common when multiple neuropsychological outcomes are evaluated in healthy individuals. Clinicians should consider the higher probability of low scores when evaluating learning and memory using various sets of scores to reduce false-positive diagnoses of cognitive deficits.