RESUMO
We used principal component analysis (PCA) to examine the component structure of a neuropsychological test battery administered to 943 cognitively-normal adults enrolled in the Southern Illinois University (SIU) Longitudinal Cognitive Aging Study (LCAS). Four components explaining the most variance (63.9%) in the dataset were identified: speed/cognitive flexibility, visuospatial skills, word-list learning/memory, and story memory. Regression analyses confirmed that increased age was associated with decreased component scores after controlling for gender and education. Our identified components differ slightly from previous studies using PCA on similar test batteries. Factors such as the demographic characteristics of the study sample, the inclusion of mixed patient and control samples, the inclusion of different test measures in previous studies, and the fact that many neuropsychological test measures assess multiple cognitive processes simultaneously, may help to explain these inconsistencies.
RESUMO
The present study examined the relationship between entorhinal cortex and hippocampal volume with fMRI activation during episodic memory function in elderly controls with no cognitive impairment and individuals with amnesic mild cognitive impairment (aMCI). Both groups displayed limited evidence for a relationship between hippocampal volume and fMRI activation. Smaller right entorhinal cortex volume was correlated with reduced activation in left and right medial frontal cortex (BA 8) during incidental encoding for both aMCI and elderly controls. However, during recognition, smaller left entorhinal cortex volume correlated with reduced activation in right BA 8 for the control group, but greater activation for the aMCI group. There was no significant relationship between entorhinal cortex volume and activation during intentional encoding in either group. The recognition-related dissociation in structure/function relationships in aMCI paralleled our behavioral findings, where individuals with aMCI displayed poorer performance relative to controls during recognition, but not encoding. Taken together, these results suggest that the relationship between entorhinal cortex volume and fMRI activation during episodic memory function is altered in individuals with aMCI.
Assuntos
Amnésia/fisiopatologia , Amnésia/psicologia , Encéfalo/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Córtex Entorrinal/patologia , Memória , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Amnésia/diagnóstico , Transtornos Cognitivos/diagnóstico , Feminino , Lobo Frontal/fisiopatologia , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Reconhecimento Psicológico , Índice de Gravidade de DoençaRESUMO
BACKGROUND/AIMS: Previous functional MRI studies in individuals with amnestic mild cognitive impairment (AMCI), a putative, prodromal form of Alzheimer's disease, reveal substantial regional changes in brain activation during episodic memory function. METHODS: Functional MRI was applied to examine changes in brain activation during different stages of episodic memory function using a subsequent memory task in individuals with AMCI relative to older normal controls. RESULTS: We found that the AMCI group displayed greater activation in the right hippocampus but less activation in the frontal cortex relative to the older normal control group during intentional encoding of items that were subsequently recognized. We observed nearly the opposite pattern of results for successful recognition. The AMCI group displayed less activation in the medial temporal cortex but greater activation in the frontal cortex. In addition, the AMCI group showed reduced activation in the medial temporal and frontal cortices during incidental encoding of novel information during recognition. CONCLUSION: The results of the present study suggest that brain activation differences in individuals with AMCI are modulated by the stage of episodic memory examined (i.e. intentional vs. incidental encoding vs. recognition). These observations may help to clarify some of the conflicting findings regarding brain activation changes in AMCI.
Assuntos
Envelhecimento , Amnésia/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Imageamento por Ressonância Magnética , Rememoração Mental/fisiologia , Reconhecimento Psicológico/fisiologia , Idoso , Doença de Alzheimer/fisiopatologia , Feminino , Lobo Frontal/fisiopatologia , Hipocampo/fisiopatologia , Humanos , Masculino , Índice de Gravidade de Doença , Lobo Temporal/fisiopatologiaRESUMO
In the present study, we used fMRI to examine the influence of age on two other known risk factors for Alzheimer's disease (AD), APOE genotype and parental history of AD (FH status), during episodic encoding (ENC) and metacognitive self-appraisal (SA) paradigms. These paradigms have previously been shown to evoke activity from brain regions that are implicated in AD. First we examined the effect of age across the adult lifespan (age 18-84 years) on cerebral activity in a large sample (n=231) of cognitively healthy individuals. Next we examined a subset (n=155) on whom APOE status and FH status were known. For ENC, we found that increasing age was associated with reduced activity in the ventral temporal lobes and hippocampus. Our analysis of risk factors suggested that FH and age exerted independent effects, but APOE interacted with age such that APOE e4 carriers exhibit age-related increases in activity in the hippocampus. For the metacognitive SA task, increasing age was found to be associated with reduced activity in the medial prefrontal cortex, and increased activity in the mesial temporal lobe, posterior orbital cortex and striatum. Neither AD risk factor significantly modified age-related changes in brain activity during SA. These results suggest that FH and aging are exerting independent effects in both tasks while APOE affected the relationship with age in the hippocampus in one of the two tasks given.
Assuntos
Doença de Alzheimer/fisiopatologia , Mapeamento Encefálico , Encéfalo/irrigação sanguínea , Cognição/fisiologia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Feminino , Genótipo , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Tempo de Reação , Fatores de RiscoRESUMO
Neuropathological and experimental animal studies indicate that traumatic brain injury (TBI) results in long-term, neurodegenerative changes. Structural image evaluation using normalization of atrophy (SIENA) offers an automated analysis of the subtle changes in percent brain volume change (%BVC) associated with TBI. In the present study, SIENA was used to evaluate %BVC in individuals who had sustained a mild to severe TBI. We obtained three-dimensional (3D) T1-weighted anatomical magnetic resonance imaging (MRI) scans approximately 79 days and again 409 days post-injury. TBI patients (n = 37) displayed significantly greater decline in %BVC (-1.43%) relative to a normal comparison group (+0.1%, n = 30). Greater %BVC was associated with longer duration of post-injury coma. These results confirm previous findings from cross-sectional studies and argue that the brain undergoes continued structural change for several months post-injury.
Assuntos
Atrofia/patologia , Atrofia/fisiopatologia , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Coma/patologia , Coma/fisiopatologia , Adulto , Fatores Etários , Atrofia/etiologia , Lesões Encefálicas/complicações , Coma/etiologia , Progressão da Doença , Escolaridade , Feminino , Escala de Coma de Glasgow , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Fatores Sexuais , Fatores de Tempo , Degeneração Walleriana/etiologia , Degeneração Walleriana/patologia , Degeneração Walleriana/fisiopatologiaRESUMO
Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.
Assuntos
Agnosia/etiologia , Agnosia/patologia , Córtex Cerebral/patologia , Transtornos Cognitivos/complicações , Autoimagem , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Estudos de Casos e Controles , Córtex Cerebral/irrigação sanguínea , Transtornos Cognitivos/psicologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Oxigênio/sangue , Análise de Regressão , Índice de Gravidade de DoençaRESUMO
Osteopontin (OPN) is a glycophosphoprotein expressed by several cell types and has pro-adhesive, chemotactic, and cytokine-like properties. OPN is involved in a number of physiologic and pathologic events including angiogenesis, apoptosis, inflammation, oxidative stress, remyelination, wound healing, bone remodeling, cell migration and tumorigenesis. Since these functions of OPN, and the events that it regulates, are involved with neurodegeneration, we examined whether OPN was differentially expressed in the hippocampus of the Alzheimer's disease (AD) compared with age-matched (59-93 years) control brain. We report for the first time the immunocytochemical localization of OPN in the cytoplasm of pyramidal neurons. In AD brains, there was a significant 41 % increase in the expression of neuron OPN compared with age-matched control brain. No staining of other neuronal cell types was observed. Additionally, there was a significant positive correlation between OPN staining intensity and both amyloid-beta load (r(2) = 0.25; P < 0.05; n = 20) and aging (r(2) = 0.32; P < 0.01; n = 20) among all control and AD subjects. Controlling for age indicated that OPN expression was significantly influenced by amyloid-beta load, but not age. While the functional consequences of this amyloid-beta associated increase in OPN expression are unclear, it is notable that OPN is primarily localized to those neurons that are known to be vulnerable to AD-related neurite loss, degeneration and death. Given that the induction of OPN expression (and amyloid-beta generation) is associated with remodeling and tumorigenesis, our results suggest that OPN may play a role in the aberrant re-entry of neurons into the cell cycle and/or neuronal remyelination in AD.
Assuntos
Doença de Alzheimer/patologia , Regulação da Expressão Gênica , Osteopontina/metabolismo , Células Piramidais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Contagem de Células , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
Voxel-based morphometry (VBM) was used to examine the relationship between gray matter (GM) volume and performance on two commonly used clinical neuropsychological measures of frontal lobe or executive function, the Trail Making Test part B (TrailsB) and the Controlled Oral Word Association Test (COWAT) in 221 cognitively healthy adults between the ages of 18 and 84. We hypothesized that these measures would be associated with GM volume in the dorsolateral frontal lobes. Voxel-based multiple regression was used to correlate cognitive function with modulated GM probability maps while controlling for age, education, gender, and total intracranial volume. A relationship with TrailsB was found in bilateral lateral inferior frontal gyri and left basal ganglia. A relationship with COWAT was found in the left lateral inferior and middle frontal gyri. Lesion studies have long implicated the importance of these regions for executive function. The present results confirm and extend those prior findings to healthy adults.
RESUMO
First-degree family history of sporadic Alzheimer disease (AD) and the apolipoprotein E epsilon4 (APOE4) are risk factors for developing AD. Although the role of APOE4 in AD pathogenesis has been well studied, family history remains a rarely studied and poorly understood risk factor. Both putatively cause early brain changes before symptomatic disease, but the relative contribution of each to brain function is unknown. We examined 68 middle-aged participants with a parent diagnosed with AD [family history (+FH)] and 64 age- and education-matched controls without a first-degree family history of any dementia [no family history (-FH)]. All underwent cognitive testing, APOE genotyping, and a functional magnetic resonance imaging encoding task that required discrimination of novel items from previously learned items. A 2 x 2 factorial ANOVA (presence/absence of parental family history and presence/absence of the APOE4) was used to detect group effects. A greater response to novel items was detected in the mesial temporal lobe and fusiform gyrus bilaterally among persons without a first-degree family history of AD. In hippocampal areas, the -FH +epsilon4 group exhibited the greatest signal change, and the +FH +epsilon4 group exhibited the least. These findings indicate that FH of AD is an important predictor of hippocampal activation during encoding and that FH may modulate the effect of APOE4 in these middle-aged adults, suggesting that an as yet unspecified factor embodied in first-degree family history of AD is influencing the expression of APOE4 on brain function.
Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Cognição/fisiologia , Lobo Temporal/fisiopatologia , Doença de Alzheimer/epidemiologia , Apolipoproteína E4 , Mapeamento Encefálico , Família , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sistema de RegistrosRESUMO
BACKGROUND: The presence of the apolipoprotein E (APOE) epsilon4 allele is a major risk factor for the development of Alzheimer's disease (AD), and has been associated with metabolic brain changes several years before the onset of typical AD symptoms. Functional MRI (fMRI) is a brain imaging technique that has been used to demonstrate hippocampal activation during measurement of episodic encoding, but the effect of the epsilon4 allele on hippocampal activation has not been firmly established. METHODS: The present study examined the effects of APOE genotype on brain activation patterns in the medial temporal lobe (MTL) during an episodic encoding task using a well-characterized novel item versus familiar item contrast in cognitively normal, middle-aged (mean = 54 years) individuals who had at least one parent with AD. RESULTS: We found that epsilon3/4 heterozygotes displayed reduced activation in the hippocampus and MTL compared to epsilon3/3 homozygotes. There were no significant differences between the groups in age, education or neuropsychological functioning, suggesting that the altered brain activation seen in epsilon3/4 heterozygotes was not associated with impaired cognitive function. We also found that participants' ability to encode information on a neuropsychological measure of learning was associated with greater activation in the anterior MTL in the epsilon3/3 homozygotes, but not in the epsilon3/4 heterozygotes. CONCLUSION: Together with previous studies reporting reduced glucose metabolism and AD-related neuropathology, this study provides convergent validity for the idea that the MTL exhibits functional decline associated with the APOE epsilon4 allele. Importantly, these changes were detected in the absence of meaningful neuropsychological differences between the groups. A focus of ongoing work in this laboratory is to determine if these findings are predictive of subsequent cognitive decline.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Apolipoproteínas E/genética , Hipocampo/fisiopatologia , Adulto , Idoso , Alelos , Cognição/fisiologia , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Heterozigoto , Hipocampo/anatomia & histologia , Humanos , Aprendizagem/fisiologia , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco , Lobo Temporal/anatomia & histologia , Lobo Temporal/fisiopatologiaRESUMO
Pavlovian delay conditioning, in which a conditioned stimulus (CS) and unconditioned stimulus (US) co-terminate, is thought to reflect non-declarative memory. In contrast, trace conditioning, in which the CS and US are temporally separate, is thought to reflect declarative memory. Hippocampal lesions impair acquisition and expression of trace conditioning measured by the conditioned freezing and eyeblink responses, while having little effect on the acquisition of delay conditioning. Recent evidence suggests that lesions of the ventral hippocampus (VH) impair conditioned fear under conditions in which dorsal hippocampal (DH) lesions have little effect. In the present study, we examined the time-course of fear expression after delay and trace conditioning using the fear-potentiated startle (FPS) reflex, and the effects of pre- and post-training lesions to the VH and DH on trace-conditioned FPS. We found that both delay- and trace-conditioned rats displayed significant FPS near the end of the CS relative to the unpaired control group. In contrast, trace-conditioned rats displayed significant FPS throughout the duration of the trace interval, whereas FPS decayed rapidly to baseline after CS offset in delay-conditioned rats. In experiment 2, both DH and VH lesions were found to significantly reduce the overall magnitude of FPS compared to the control group, however, no differences were found between the DH and VH groups. These findings support a role for both the DH and VH in trace fear conditioning, and suggest that the greater effect of VH lesions on conditioned fear might be specific to certain measures of fear.
Assuntos
Aprendizagem por Associação/fisiologia , Lesões Encefálicas/fisiopatologia , Condicionamento Clássico/fisiologia , Medo , Hipocampo/fisiopatologia , Reflexo de Sobressalto/fisiologia , Animais , Aprendizagem por Associação/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Lesões Encefálicas/induzido quimicamente , Condicionamento Clássico/efeitos dos fármacos , Hipocampo/patologia , Masculino , N-Metilaspartato , Ratos , Ratos Sprague-Dawley , Reflexo de Sobressalto/efeitos dos fármacos , Fatores de TempoRESUMO
BACKGROUND: Several previous studies have reported that amnestic mild cognitive impairment (aMCI), a significant risk factor for Alzheimer's disease (AD), is associated with greater atrophy in the medial temporal lobe (MTL) and posterior cingulate gyrus (PCG). METHOD: In the present study, we examined the cross-sectional accuracy (i.e., the sensitivity and specificity) of voxel-based morphometry (VBM) in discriminating individuals with MCI (n =15) from healthy age-matched controls (n =15). In addition, we also sought to determine whether baseline GM volume predicted aMCI patients that converted to AD from those that did not approximately 2 years after the baseline visit. RESULTS: MCI patients were found to display significantly less GM volume in several hypothesized regions including the MTL and PCG relative to the age-matched controls (p < 0.01). Logistic regression analysis and receiver operating characteristic (ROC) curves for GM volume in the anterior MTL and PCG revealed high discriminative accuracy of 87%. By contrast, baseline GM volume in anterior MTL and PCG did not appear to be sensitive to changes in clinical status at the follow-up visit. CONCLUSION: These results suggest that VBM might be useful at characterizing GM volume reductions associated with the diagnosis of aMCI.
RESUMO
Neuroimaging research has demonstrated that the posterior cingulate cortex (PCC) is functionally compromised in individuals diagnosed with amnestic mild cognitive impairment (MCI), a major risk factor for the development of Alzheimer's disease (AD). In functional MRI studies with healthy participants, this same region is active during self-appraisal (requiring retrieval of semantic knowledge about the self) as well as episodic recognition of previously learned information. Administering both types of tasks to people with MCI may reveal important information on the role of the PCC in recollection. This study investigated fMRI activation in the PCC in individuals with MCI and matched controls across two tasks. The first task was a visual episodic recognition task. The second task was an autobiographical self-appraisal task in which subjects rated themselves on a set of trait adjectives. Results of a conjunction analysis revealed the PCC as the sole region commonly active during both tasks in the healthy older adults. Furthermore, additional analysis revealed an interaction in the PCC, indicating a task-dependent response in the MCI group. MCI participants showed PCC activation during self-appraisal, but not episodic retrieval. This result suggests in MCI that the PCC shows functional degradation during episodic retrieval; however, the PCC's role in retrieval and evaluation of highly elaborated information regarding the self is more well-preserved.
Assuntos
Transtornos Cognitivos/fisiopatologia , Giro do Cíngulo/fisiopatologia , Idoso , Transtornos Cognitivos/psicologia , Imagem Ecoplanar , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Rememoração Mental/fisiologia , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia , Reconhecimento Psicológico/fisiologia , AutoimagemRESUMO
BACKGROUND: Obesity causes or exacerbates a host of medical conditions, including cardiovascular, pulmonary, and endocrine diseases. Recently obesity in elderly women was associated with greater risk of dementia, white matter ischemic changes, and greater brain atrophy. The purpose of this study was to determine whether body type affects global brain volume, a marker of atrophy, in middle-aged men and women. METHODS: T1-weighted 3D volumetric magnetic resonance imaging was used to assess global brain volume for 114 individuals 40 to 66 years of age (average = 54.2 years; standard deviation = 6.6 years; 43 men and 71 women). Total cerebrospinal fluid and brain volumes were obtained with an automated tissue segmentation algorithm. A regression model was used to determine the effect of age, body mass index (BMI), and other cardiovascular risk factors on brain volume and cognition. RESULTS: Age and BMI were each associated with decreased brain volume. BMI did not predict cognition in this sample; however elevated diastolic blood pressure was associated with poorer episodic learning performance. CONCLUSION: These findings suggest that middle-aged obese adults may already be experiencing differentially greater brain atrophy, and may potentially be at greater risk for future cognitive decline.
Assuntos
Envelhecimento/patologia , Índice de Massa Corporal , Encéfalo/patologia , Imageamento Tridimensional , Adulto , Idoso , Envelhecimento/fisiologia , Algoritmos , Atrofia/patologia , Cognição/fisiologia , Estudos Transversais , Demografia , Feminino , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Relação Cintura-QuadrilRESUMO
The hippocampus has been suggested to be involved in spatial (or configural) memory and also in the inhibition of certain response or goal alternatives. An increasing number of anatomical, physiological, and behavioral studies indicate that the hippocampus is functionally heterogeneous along the dorsal-ventral axis. Identification of distinct behavioral roles for the dorsal (DH) and ventral (VH) hippocampus may resolve differences between the various theoretical accounts of hippocampal function. The present study examined the effects of electrolytic lesions restricted to the DH or VH on fear-conditioned freezing, passive avoidance on the elevated T-maze (ETM) test of anxiety, and general activity in male Sprague-Dawley (Charles-River derived) albino rats. We found that rats with lesions of the VH, but not DH showed reduced freezing to both context and tone conditioned stimuli (CS). Rats with VH lesions also showed a reduced latency to emerge from the enclosed arm on trials 2 and 3 of the ETM (indicating reduced anxious behavior), while having no effect on the latency to escape from the open arms on trial 4. There were no differences in activity between the groups. These results indicate that the VH and DH are differentially involved in passive avoidance on the ETM and conditioned freezing to context and tone CS. We suggest that the VH may be specifically involved in modulating goal-oriented, defensive behavior expression through hypothalamic and amygdaloid connections.
Assuntos
Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Hipocampo/fisiologia , Aprendizagem em Labirinto/fisiologia , Estimulação Acústica , Animais , Ansiedade/fisiopatologia , Medo/psicologia , Hipocinesia/psicologia , Masculino , Atividade Motora/fisiologia , Ratos , Ratos Sprague-Dawley , Tempo de ReaçãoRESUMO
We review 42 studies examining the effects of estrogen replacement therapy (ERT) on memory and cognition in nondemented postmenopausal women. Although there are an appreciable number of nonsignificant findings, the number of significant findings favoring ERT users considerably outnumbers the rare findings of better performance in controls. Experimental studies demonstrate a consistent beneficial effect on verbal memory, but these are short-term studies of the more acute effects of ERT. The observational studies suggest that there may be a long-lasting effect of continued ERT on cognitive functioning, but these studies need to be interpreted with caution because of the lack of random assignment and a possible "healthy user bias." We also summarize findings from studies on the effects of ERT on Alzheimer's disease (AD). ERT is associated with a decreased risk for dementia, but there is little evidence for a positive effect on cognition in women with AD. Definitive answers to questions about the long-term effects of ERT on cognitive aging and risk of developing AD should be provided by 3 ongoing clinical trials.