Combining Select Blood-Based Biomarkers with Neuropsychological Assessment to Detect Mild Cognitive Impairment among Mexican Americans.

BACKGROUND: Recent work has supported use of blood-based biomarkers in detection of amnestic mild cognitive impairment (MCI). Inclusion of neuropsychological measures has shown promise in enhancing utility of biomarkers to detect disease. OBJECTIVE: The present study sought to develop cognitive-biomarker profiles for detection of MCI. METHODS: Data were analyzed on 463 participants (normal control n = 378; MCI n = 85) from HABLE. Random forest analyses determined proteomic profile of MCI. Separate linear regression analyses determined variance accounted for by select biomarkers per neuropsychological measure. When neuropsychological measure with the least shared variance was identified, it was then combined with select biomarkers to create a biomarker-cognitive profile. RESULTS: The biomarker-cognitive profile was 90% accurate in detecting MCI. Among amnestic MCI cases, the detection accuracy of the biomarker-cognitive profile was 92% and increased to 94% with demographic variables. CONCLUSION: The biomarker-cognitive profile for MCI was highly accurate in its detection with use of only five biomarkers.

Maturation of newborn neurons predicts social memory persistence in mice.

Memory transience is essential to gain cognitive flexibility. Recently, hippocampal neurogenesis is emerging as one of the mechanisms involved in the balance between persistence and forgetting. Social recognition memory (SRM) has its duration prolonged by neurogenesis. However, it is still to be determined whether boosting neurogenesis in distinct phases of SRM may favor forgetting over persistence. In the present study, we used enriched environment (EE) and memantine (MEM) to increase neurogenesis. SRM was ubiquitously prolonged by both, while EE after the memory acquisition did not favor forgetting. Interestingly, the proportion of newborn neurons with mature morphology in the dorsal hippocampus was higher in animals where persistence prevailed. Finally, one of the main factors for dendritic growth is the formation of cytoskeleton. We found that Latrunculin A, an inhibitor of actin polymerization, blunted the promnesic effect of EE. Altogether, our results indicate that the mechanisms triggered by EE to improve SRM are not limited to increasing the number of newborn neurons.

The relationship between sociocultural factors and autobiographical memories from childhood: the role of formal schooling.

Cross-cultural differences in autobiographical memory (AM) are associated with cultural variations. In models of the self and parental reminiscing style, but not many studies have analysed the relationship between AM and specific cultural practices such as formal schooling. Theoreticians like [Greenfield, P. M. (2009). Linking social change and developmental change: Shifting. pathways of human development. Developmental Psychology, 45, 401-418. doi: 10.1037/a0014726 ; Kagitçibasi, C. (2005). Autonomy and relatedness in cultural context. Implications for self and family. Journal of Cross-Cultural Psychology, 36, 403-422. doi: 10.1177/0022022105275959 ] and [Keller, H. (2007). Children development across cultures. New York: Lawrence Erlbaum Associates] have considered formal schooling as an engine towards the model of independence; however, the empirical evidence in this regard is inconclusive: while some studies found evidence of a relation between formal schooling and characteristics of AM, others did not. To solve this inconsistency, the present study compared orally narrated childhood memories of Mexican adults with three different levels of education (from rudimentary literacy to university). Results support a relationship between formal schooling and AM in the predicted direction: More educated participants reported longer, more specific and more self-oriented memories than those with less schooling experience did. Some gender differences were also observed, with males generally reporting more individually and less socially oriented memories than females, except for university level participants. We conclude that these results support Greenfield's theory about formal schooling as a sociocultural factor that promotes the cultural pathway to independence, as well as complexity and context-boundedness of gender differences in AM.

Alcohol-related blackouts among college students: impact of low level of response to alcohol, ethnicity, sex, and environmental characteristics

Objective: To explore how a genetically-influenced characteristic (the level of response to alcohol [LR]), ethnicity, and sex relate to environmental and attitudinal characteristics (peer drinking [PEER], drinking to cope [COPE], and alcohol expectancies [EXPECT]) regarding future alcohol-related blackouts (ARBs). Methods: Structural equation models (SEMs) were used to evaluate how baseline variables related to ARB patterns in 462 college students over 55 weeks. Data were extracted from a longitudinal study of heavy drinking and its consequences at a U.S. university. Results: In the SEM analysis, female sex and Asian ethnicity directly predicted future ARBs (beta weights 0.10 and -0.11, respectively), while all other variables had indirect impacts on ARBs through alcohol quantities (beta weights ~ 0.23 for European American ethnicity and low LR, 0.21 for cannabis use and COPE, and 0.44 for PEER). Alcohol quantities then related to ARBs with beta = 0.44. The SEM explained 23% of the variance. Conclusion: These data may be useful in identifying college students who are more likely to experience future ARBs over a 1-year period. They enhance our understanding of whether the relationships of predictors to ARBs are direct or mediated through baseline drinking patterns, information that may be useful in prevention strategies for ARBs.

Alcohol-related blackouts among college students: impact of low level of response to alcohol, ethnicity, sex, and environmental characteristics.

Objective: To explore how a genetically-influenced characteristic (the level of response to alcohol [LR]), ethnicity, and sex relate to environmental and attitudinal characteristics (peer drinking [PEER], drinking to cope [COPE], and alcohol expectancies [EXPECT]) regarding future alcohol-related blackouts (ARBs). Methods: Structural equation models (SEMs) were used to evaluate how baseline variables related to ARB patterns in 462 college students over 55 weeks. Data were extracted from a longitudinal study of heavy drinking and its consequences at a U.S. university. Results: In the SEM analysis, female sex and Asian ethnicity directly predicted future ARBs (beta weights 0.10 and -0.11, respectively), while all other variables had indirect impacts on ARBs through alcohol quantities (beta weights ~ 0.23 for European American ethnicity and low LR, 0.21 for cannabis use and COPE, and 0.44 for PEER). Alcohol quantities then related to ARBs with beta = 0.44. The SEM explained 23% of the variance. Conclusion: These data may be useful in identifying college students who are more likely to experience future ARBs over a 1-year period. They enhance our understanding of whether the relationships of predictors to ARBs are direct or mediated through baseline drinking patterns, information that may be useful in prevention strategies for ARBs.

Vocabulary is an appropriate measure of premorbid intelligence in a sample with heterogeneous educational level in Brazil.

Crystallized intelligence refers to one's knowledge base and can be measured by vocabulary tests. Fluid intelligence is related to nonverbal aspects of intelligence, depends very little on previously acquired knowledge, and can be measured by tests such as Block Design (BD) and Raven Colored Matrices (RCM). Premorbid intelligence quotient (IQ) refers to one's intellectual ability level previous to the onset of disorders like mild cognitive impairment (MCI) and Alzheimer's disease (AD) and it is important to estimate disease severity. The objective was to compare performance in tests that measure crystallized and fluid intelligence in healthy subjects and patients with amnestic MCI (aMCI) and AD. One hundred forty-four participants (aMCI (n = 38), AD (n = 45), and healthy controls (n = 61)) were submitted to neuropsychological tests (WAIS-III vocabulary, BD, and RCM). There were significant among groups, except for vocabulary, indicating a relative stability of crystallized intelligence in the continuum from normal to pathological cognitive decline. Vocabulary seems to be stable during the progression of the disease and useful as a measure of premorbid intelligence, that is, to estimate previous function in relation to the level of education and, as a collateral measure of cognition in people with low education.

Aspectos mnésicos del envejecimiento / Mnesic aspects of aging

Los cambios cognitivos, tanto funcionales como estructurales presentes en el envejecimiento, son complejos y variados. En un sentido general, se ha encontrado asociado a esta etapa del ciclo vital un declive de gran parte de las funciones cerebrales; en relación a ello un estudio realizado por Román y Sánchez (1998) demostró que no sólo se produce un deterioro, sino que también se mantienen o se potencializan otros procesos cognitivos. Aunque las alteraciones se presentan en la mayoría de las funciones, es de especial interés exponer aquí, aquellas que se involucran con los procesos mnésicos; teniendo en cuenta que se ven afectados en el adulto mayor.

The cognitive changes, both functional and structural, present in aging are complex and varied. In a general sense, a decline in a large part of brain functions has been found associated with this stage of the life cycle; In relation to this, a study carried out by Román and Sánchez (1998) showed that not only deterioration occurs, but also that other cognitive processes are maintained or enhanced. Although the alterations are present in most of the functions, it is of special interest to expose here, those that are involved with the mnesic processes; taking into account that they are affected in the elderly.

Cognitive intervention in amnestic Mild Cognitive Impairment: a systematic review.

Mild Cognitive Impairment (MCI) represents a transitional state between normal aging and early dementia and is commonly associated with memory impairment (amnestic or A-MCI). Several studies have investigated therapeutic approaches to A-MCI, including cholinestherase inhibitors (I-ChEs), although this practice is still controversial. Thus, there is a current need to determine the effects of cognitive interventions either in combination with I-ChEs or alone. To assess the efficacy of such treatments, neuropsychological instruments and self-evaluated scoring of memory, mood, daily life activities and quality of life are employed. Recently, some studies have used functional magnetic resonance imaging (fMRI) in order to understand the neurobiological effects of these interventions. The aim of this systematic review is to investigate the effectiveness of cognitive interventions on the enhancement of learning abilities as well as their impacts on cognitive measurements of mood, everyday functioning and functional neuroimaging. This review also focused on the methodological aspects of such studies and attempted to introduce new perspectives on cognitive interventions in this population. The authors concluded that a-MCI patients are capable to learn new information and memory strategies. Although findings in standardized neuropsychological tests are limited, non-standardized cognitive measures and subjective measures show significant changes. Furthermore, fMRI reveals changes in the patterns of brain activation and increase of connectivity.

Incidence of mild cognitive impairment: a systematic review.

BACKGROUND/AIMS: Subjects with mild cognitive impairment (MCI) constitute a risk population of developing dementia and thus a population of clinical interest. This study reviews recent work on the incidence of MCI in the elderly. METHODS: Incidence papers were identified by a systematic literature search. Studies on the incidence of MCI were considered if they identified 'cognitively mildly impaired' subjects by application of the MCI criteria, used the 'person-years-at-risk' method, and were based on population- or community-based samples. RESULTS: Nine studies were identified. The incidence of amnestic MCI subtypes ranged between 9.9 and 40.6 per 1,000 person-years, and the incidence of non-amnestic MCI subtypes was 28 and 36.3 per 1,000 person-years. Regarding any MCI, incidence rates of 51 and 76.8 per 1,000 person-years were found. A higher risk of incident MCI mainly resulted for higher age, lower education and hypertension. DISCUSSION: The incidence rates of MCI varied widely, and possible risk factors for incident MCI were analysed only to a limited extent. The findings call for an agreement concerning the criteria used for MCI and the operationalisation of these criteria.

Chronic stress is associated with high cortisol levels and emotional coping mechanisms in amnestic mild cognitive impairment.

BACKGROUND/AIMS: To investigate the association between cortisol levels, chronic stress and coping in subjects with amnestic-type mild cognitive impairment (aMCI). METHODS: Cortisol levels were measured using morning saliva samples from 33 individuals with aMCI and from 41 healthy elderly. Chronic stress was evaluated with the Stress Symptoms List (SSL), whereas coping strategies were assessed using the Jalowiec Coping Scale. RESULTS: aMCI subjects with high SSL scores presented higher cortisol levels (p = 0.045). Furthermore, aMCI subjects who employed emotion-focused coping had higher SSL scores (p = 0.023). CONCLUSION: The association between increased cortisol secretion, chronic stress and coping strategies may be modulated by the presence or absence of cognitive impairment, where memory defi- cit awareness constitutes an additional potential factor involved in high stress severity.

MK801- and scopolamine-induced amnesias are reversed by an Amazonian herbal locally used as a "brain tonic".

RATIONALE: Traditional remedies prepared from Ptychopetalum olacoides (PO) are used throughout the Amazon to alleviate age-related conditions. These formulas are mainly used by elders, and alleged effects may be related to the anticholinesterase properties identified in a standardized ethanol extract of this species [P. olacoides standardized ethanol extract (POEE)]. OBJECTIVES: To further characterize the potential of this extract for developing drugs useful to treat cognitive deficits, the effects of POEE on scopolamine (scop)- and MK801-induced amnesias (acquisition, consolidation, and retrieval) in mice were investigated. RESULTS: Scop (3.0 mg/kg, ip) significantly impaired memory (all three phases) in the step-down inhibitory avoidance protocol. As expected, MK801 (0.1 mg/kg, ip) was amnesic regarding acquisition and consolidation, but not retrieval. POEE (100 mg/kg, ip) reversed the scop-induced impairment in all three phases of long-term and short memories, whereas only the memory consolidation deficit was reversed with MK801-induced amnesia. CONCLUSIONS: This study complements previously reported promnesic properties of this plant extract and suggests that POEE may be further developed for treating conditions associated with cognitive deficits, especially those linked with cholinergic malfunction.

Semantic error patterns on the Boston Naming Test in normal aging, amnestic mild cognitive impairment, and mild Alzheimer's disease: is there semantic disruption?

Naming difficulty is common in Alzheimer's disease (AD), but the nature of this problem is not well established. The authors investigated the presence of semantic breakdown and the pattern of general and semantic errors in patients with mild AD, patients with amnestic mild cognitive impairment (aMCI), and normal controls by examining their spontaneous answers on the Boston Naming Test (BNT) and verifying whether they needed or were benefited by semantic and phonemic cues. The errors in spontaneous answers were classified in four mutually exclusive categories (semantic errors, visual paragnosia, phonological errors, and omission errors), and the semantic errors were further subclassified as coordinate, superordinate, and circumlocutory. Patients with aMCI performed normally on the BNT and needed fewer semantic and phonemic cues than patients with mild AD. After semantic cues, subjects with aMCI and control subjects gave more correct answers than patients with mild AD, but after phonemic cues, there was no difference between the three groups, suggesting that the low performance of patients with AD cannot be completely explained by semantic breakdown. Patterns of spontaneous naming errors and subtypes of semantic errors were similar in the three groups, with decreasing error frequency from coordinate to superordinate to circumlocutory subtypes.

Ex vivo study of 5-HT(1A) and 5-HT(7) receptor agonists and antagonists on cAMP accumulation during memory formation and amnesia.

The cyclic adenosine monophosphate (cAMP) is a second messenger and a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Hence, in this work, firstly the time-course of memory formation was determined in an autoshaping learning task, which had allowed the identification of testing times for increases or decreases in performance. Next, untrained, trained and overtrained groups were compared in cAMP production. Moreover, selective stimulation and antagonism of 5-HT(1A) and 5-HT(7) receptors during memory formation and cAMP production were determined. Finally, since there is scarce information about how pharmacological models of amnesia affect cAMP production, the cholinergic or glutamatergic antagonists, scopolamine and dizocilpine, were tested. The major findings of this work showed that when the time-course was determined inasmuch as training and testing sessions occurred, memory performance was graduate and progressive. Notably, for the fourth to seventh (i.e., 48-120 h following autoshaping training session) testing session performance was significantly higher from the previous ones. When animals received 5-HT(1A) and 5-HT(7) receptor agonists and antagonists or amnesic drugs significant increases or decrements in memory performance were observed at 24 and 48 h. Moreover, when ex vivo cAMP production from trained and overtrained groups were compared to untrained ones, significant differences were observed among groups and brain areas. Trained animals treated with 8-OHDPAT, AS19, 8-OHDPAT plus AS19, WAY100635, SB-269970, scopolamine or dizocilpine were compared to similar untrained groups, and eightfold-reduced cAMP production was evident, showing the importance of cAMP production in the signaling case in mammalian memory formation.

Lexical semantic memory in amnestic mild cognitive impairment and mild Alzheimer's disease.

OBJECTIVE: To study lexical semantic memory in patients with amnestic mild cognitive impairment (aMCI), mild Alzheimer's disease (AD) and normal controls. METHOD: Fifteen mild AD, 15 aMCI, and 15 normal control subjects were included. Diagnosis of AD was based on DSM-IV and NINCDS-ADRDA criteria, and that of aMCI, on the criteria of the International Working Group on Mild Cognitive Impairment, using CDR 0.5 for aMCI and CDR 1 for mild AD. All subjects underwent semantic memory tests (Boston Naming-BNT, CAMCOG Similarities item), Rey Auditory Verbal Learning Test (RAVLT), Mini-Mental Status Examination (MMSE), neuropsychological tests (counterproofs), and Cornell Scale for Depression in Dementia. Data analysis used Mann-Whitney test for intergroup comparisons and Pearson's coefficient for correlations between memory tests and counterproofs (statistical significance level was p<0.05). RESULTS: aMCI patients were similar to controls on BNT and Similarities, but worse on MMSE and RAVLT. Mild AD patients scored significantly worse than aMCI and controls on all tests. CONCLUSION: aMCI impairs episodic memory but tends to spare lexical semantic system, which can be affected in the early phase of AD.

Lexical semantic memory in amnestic mild cognitive impairment and mild Alzheimer's disease

OBJECTIVE: To study lexical semantic memory in patients with amnestic mild cognitive impairment (aMCI), mild Alzheimer's disease (AD) and normal controls. METHOD: Fifteen mild AD, 15 aMCI, and 15 normal control subjects were included. Diagnosis of AD was based on DSM-IV and NINCDS-ADRDA criteria, and that of aMCI, on the criteria of the International Working Group on Mild Cognitive Impairment, using CDR 0.5 for aMCI and CDR 1 for mild AD. All subjects underwent semantic memory tests (Boston Naming-BNT, CAMCOG Similarities item), Rey Auditory Verbal Learning Test (RAVLT), Mini-Mental Status Examination (MMSE), neuropsychological tests (counterproofs), and Cornell Scale for Depression in Dementia. Data analysis used Mann-Whitney test for intergroup comparisons and Pearson's coefficient for correlations between memory tests and counterproofs (statistical significance level was p<0.05). RESULTS: aMCI patients were similar to controls on BNT and Similarities, but worse on MMSE and RAVLT. Mild AD patients scored significantly worse than aMCI and controls on all tests. CONCLUSION: aMCI impairs episodic memory but tends to spare lexical semantic system, which can be affected in the early phase of AD.

OBJETIVO: Estudar a memória léxico-semântica no comprometimento cognitivo leve amnéstico (aCCL), doença de Alzheimer (DA) leve e controles normais. MÉTODO: Incluímos 15 pacientes com DA leve, 15 com aCCL e 15 controles normais, usando os critérios DSM-IV, NINCDS-ADRDA e CDR 1 para DA, e os do International Working Group on Mild Cognitive Impairment, e CDR 0,5 para aCCL. Todos os sujeitos passaram por testes de memória semântica (Teste de nomeação de Boston - TNB, item de Similaridades do CAMCOG), teste de aprendizado auditivo-verbal de Rey (TAAVR), Mini-Exame do Estado Mental (MEEM), testes neuropsicológicos (contraprovas) e Escala Cornell para Depressão em Demência. A análise dos dados usou o teste de Mann-Whitney para comparações entre os grupos e o coeficiente de Pearson para correlação entre testes e contraprovas (nível de significância p<0,05). RESULTADOS: Os pacientes com aCCL foram semelhantes aos controles no TNB e Similaridades, mas inferiores no MEEM e TAAVR. Pacientes com DA leve tiveram performance inferior à de sujeitos com aCCL e controles em todos os testes. CONCLUSÃO: O aCCL prejudica a memória episódica, mas tende a poupar o sistema léxico-semântico, que pode estar afetado na fase inicial da DA.

Phosphorylation of extra-nuclear ERK/MAPK is required for long-term memory consolidation in the crab Chasmagnathus.

It was previously demonstrated that mitogen-activated protein kinase (MAPK) signaling plays a pivotal role in neural plasticity and memory processes both in rodents and mollusks. Although the MAPK pathways are highly conserved, no evidence was found for its participation in memory models in other animal groups. Here we found ERK-like and JNK-like cross-immunoreactivity in the crab brain with phospho-specific antibodies and we estimated ERK and JNK activity during long-term memory consolidation in the context-signal learning paradigm of the crab Chasmagnathus. At 0, 1, 3 and 6h after training ERK and JNK activity was measured. ERK-like activation was found 1h after spaced training in cytosolic but not in nuclear fractions of brain homogenates, while JNK activity remained unchanged in both fractions. Passive (context exposure) and active (continuous stimulation) controls showed cytosolic ERK and JNK activation immediately after training, which decayed 1h later. In coincidence with this time course of activity, an ERK1/2 pathway inhibitor, PD098059, induced amnesia only when administered 45 min after training but not when administered immediately pre- or post-training. These data support that: (1) cytoplasmic but not nuclear ERK substrates must be differentially phosphorylated during memory consolidation, and (2) ERK phosphorylation and consequent activation 1h after training is necessary for long-term memory consolidation in this arthropod model.

Activation of the transcription factor NF-kappaB by retrieval is required for long-term memory reconsolidation.

Several studies support that stored memories undergo a new period of consolidation after retrieval. It is not known whether this process, termed reconsolidation, requires the same transcriptional mechanisms involved in consolidation. Increasing evidence supports the participation of the transcription factor NF-kappaB in memory. This was initially demonstrated in the crab Chasmagnathus model of associative contextual memory, in which re-exposure to the training context induces a well characterized reconsolidation process. Here we studied the role of NF-kappaB in reconsolidation. NF-kappaB was specifically activated in trained animals re-exposed to the training context but not to a different context. NF-kappaB was not activated when animals were re-exposed to the context after a weak training protocol insufficient to induce long-term memory. A specific inhibitor of the NF-kappaB pathway, sulfasalazine, impaired reconsolidation when administered 20 min before re-exposure to the training context but was not effective when a different context was used. These findings indicate for the first time that NF-kappaB is activated specifically by retrieval and that this activation is required for memory reconsolidation, supporting the view that this molecular mechanism is required in both consolidation and reconsolidation.