Voxel-based morphometry findings in Alzheimer's disease: neuropsychiatric symptoms and disability correlations - preliminary results

INTRODUCTION: The role of structural brain changes and their correlations with neuropsychiatric symptoms and disability in Alzheimer's disease are still poorly understood. OBJECTIVE: To establish whether structural changes in grey matter volume in patients with mild Alzheimer's disease are associated with neuropsychiatric symptoms and disability METHODS: Nineteen Alzheimer's disease patients (9 females; total mean age =75.2 y old +4.7; total mean education level =8.5 y +4.9) underwent a magnetic resonance imaging (MRI) examination and voxel-based morphometry analysis. T1-weighted images were spatially normalized and segmented. Grey matter images were smoothed and analyzed using a multiple regression design. The results were corrected for multiple comparisons. The Neuropsychiatric Inventory was used to evaluate the neuropsychiatric symptoms, and the Functional Activities Questionnaire and Disability Assessment for Dementia were used for functional evaluation RESULTS: A significant negative correlation was found between the bilateral middle frontal gyri, left inferior temporal gyrus, right orbitofrontal gyrus, and Neuropsychiatric Inventory scores. A negative correlation was found between bilateral middle temporal gyri, left hippocampus, bilateral fusiform gyri, and the Functional Activities Questionnaire. There was a positive correlation between the right amygdala, bilateral fusiform gyri, right anterior insula, left inferior and middle temporal gyri, right superior temporal gyrus, and Disability Assessment for Dementia scores CONCLUSIONS: The results suggest that the neuropsychiatric symptoms observed in Alzheimer's disease patients could be mainly due to frontal structural abnormalities, whereas disability could be associated with reductions in temporal structures.

Increased levels of glutamate in the central nervous system are associated with behavioral symptoms in experimental malaria

Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has been associated with cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM are incompletely understood. Glutamate and other metabolites such as lactate have been implicated in its pathogenesis. In the present study, we investigated the involvement of glutamate in the behavioral symptoms of CM. Seventeen female C57BL/6 mice (20-25 g) aged 6-8 weeks were infected with P. berghei ANKA by the intraperitoneal route using a standardized inoculation of 10(6) parasitized red blood cells suspended in 0.2 mL PBS. Control animals (N = 17) received the same volume of PBS. Behavioral and neurological symptoms were analyzed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. Glutamate release was measured in the cerebral cortex and cerebrospinal fluid of infected and control mice by fluorimetric assay. All functional categories of the SHIRPA battery were significantly altered in the infected mice at 6 days post-infection (dpi) (P ≤ 0.05). In parallel to CM symptoms, we found a significant increase in glutamate levels in the cerebral cortex (mean ± SEM; control: 11.62 ± 0.90 nmol/mg protein; infected at 3 dpi: 10.36 ± 1.17 nmol/mg protein; infected at 6 dpi: 26.65 ± 0.73 nmol/mg protein; with EGTA, control: 5.60 ± 1.92 nmol/mg protein; infected at 3 dpi: 6.24 ± 1.87 nmol/mg protein; infected at 6 dpi: 14.14 ± 0.84 nmol/mg protein) and in the cerebrospinal fluid (control: 128 ± 51.23 pmol/mg protein; infected: 301.4 ± 22.52 pmol/mg protein) of infected mice (P ≤ 0.05). These findings suggest a role of glutamate in the central nervous system dysfunction found in CM.

Psychotic and behavioral symptoms in Alzheimer's disease: neuropsychological correlations

La aparición de sintomas psicóticos y conductales y el compromiso neuropsicológico fueron estudiados en 35 pacientes con diagnóstico de Enfermedad de Alzheimer Probable ( segun criterios del NINCDS-ADRDA) utilizando la Escala de Trastornos Conductales de Reisberg y cols. y una extensa batería de tests neuropsicológicos. Once pacientes, libres de trastornos psicológicos y conductales, presentaron puntajes más alto en el MMSE y en el Aphasia Screening Test, scores más bajos en la Escala de Demencia de Blessed y estadios más precoces en la Escala de Deterioro Global de Reisberg que los 24 pacientes con síntomas psicóticos o conductuales. Ambos grupos de pacientes no presentaron diferencias significativas en el Trailmaking Test, Span de dígitos y Construcciones. Delirios de robo, celotípicos, por falsos reconocimientos ( Sindrome de Capgras), agitación e intranquilidad motora son los trastornos que mostraron significativa correlación con baja performance cognitiva, especialmente en tests de memoria verbal, Token Test, Aphasia Screening Test, Trailmaking y Nominación por confrontación Visual. Por el contrario, la agresividad verbal (y/o física) y el delirio de abandono se correlacionan significativamente con evidencias de mejor performance cognitiva y menor pérdida de memoria. Se concluye que los síntomas sicóticos y conductuales asociados a la Enfermedad de Alzheimer pueden ser analizados en dos grupos: un grupo formado por agresividad verbal o física y delirios de abandono correlacionado con mejor performance neuropsicológica y menor duración de los síntomas cognitivos