Safety and tolerability of lumbar puncture for the evaluation of Alzheimer's disease.

Introduction: Lumbar puncture (LP) to collect and examine cerebrospinal fluid (CSF) is an important option for the evaluation of Alzheimer's disease (AD) biomarkers but it is not routinely performed due to its invasiveness and link to adverse effects (AE). Methods: We include all participants who received at least one LP in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Study. For comparison between groups, two-sample t-tests for continuous, and Pearson's chi-square test for categorical variables were performed. Results: Two hundred twenty-seven LP-related AEs were reported by 172 participants after 1702 LPs (13.3%). The mean age of participants who reported at least one AE was 69.79 (standard deviation (SD) 6.3) versus none 72.44 (7.17) years (p < 0.001) with female predominance (115/172 = 67.4% vs 435/913 = 48%), and had greater entorhinal cortical thickness and hippocampal volume (3.903 (0.782) vs 3.684 (0.775) mm, p = 0.002; 7.38 (1.06) vs 7.05 (1.15) mm3, p < 0.001), respectively. Discussion: We found that younger age, female sex, and greater thickness of the entorhinal cortex were associated with a higher rate of LP-related AE reports.

Altered inflammatory activity associated with reduced hippocampal volume and more severe posttraumatic stress symptoms in Gulf War veterans.

BACKGROUND: Inflammation may reduce hippocampal volume by blocking neurogenesis and promoting neurodegeneration. Posttraumatic stress disorder (PTSD) has been linked with both elevated inflammation and reduced hippocampal volume. However, few studies have examined associations between inflammatory markers and hippocampal volume, and none have examined these associations in the context of PTSD. METHODS: We measured levels of the inflammatory markers interleukin-6 (IL-6) and soluble receptor II for tumor necrosis factor (sTNF-RII) as well as hippocampal volume in 246 Gulf War veterans with and without current and past PTSD as assessed with the Clinician Administered PTSD Scale (CAPS). Enzyme-linked immunosorbent assays were used to measure inflammatory markers, and 1.5Tesla magnetic resonance imaging (MRI) and Freesurfer version 4.5 were used to quantify hippocampal volume. Hierarchical linear regression and analysis of covariance models were used to examine if hippocampal volume and PTSD status would be associated with elevated levels of IL-6 and sTNF-RII. RESULTS: Increased sTNF-RII, but not IL-6, was significantly associated with reduced hippocampal volume (ß=-0.14, p=0.01). The relationship between sTNF-RII and hippocampal volume was independent of potential confounds and covariates, including PTSD status. Although we observed no PTSD diagnosis-related differences in either IL-6 or sTNF-RII, higher PTSD severity was associated with significantly increased sTNF-RII (ß=0.24, p=0.04) and reduced IL-6 levels (ß=-0.24, p=0.04). CONCLUSIONS: Our results indicate that specific inflammatory proteins may be associated with brain structure and function as indexed by hippocampal volume and PTSD symptoms.

Patterns of frontal lobe atrophy in frontotemporal dementia: a volumetric MRI study.

OBJECTIVES: Frontotemporal dementia (FTD), the second commonest degenerative cause of dementia under the age of 65, often presents with striking changes in behaviour and personality in association with frontal lobe atrophy. Based on the behavioural changes observed in FTD, it is commonly assumed that the orbitofrontal cortex is the earliest and most severely affected frontal sub-region. However, evidence to support this assumption has to date been largely lacking. METHODS: Using a novel volumetric MRI method, we performed a detailed volumetric analysis of six frontal regions in 12 subjects with the frontal or behavioural variant of FTD (fvFTD) and 12 age-, education- and sex-matched normal controls. The regions studied were: the orbitofrontal and insula regions (representing the orbitobasal cortex); the inferior and middle frontal regions (representing the dorsolateral prefrontal areas); and the superior frontal and anterior cingulate regions (representing the medial prefrontal areas). RESULTS: As a group, the fvFTD patients showed atrophy involving all six regions. We then segregated the 12 patients into three sub-groups according to their overall degree of atrophy. In the mildest group (n = 3) all regions fell within 2 standard deviations of normal. In the intermediate group (n = 6) only the orbitofrontal region (bilaterally) fell clearly outside the control range (>2 z scores below the control mean); the next most atrophic region in this group was the right insular region. The severe group (n = 3) had generalized atrophy throughout the frontal regions measured. CONCLUSIONS: In conclusion, patients with the earliest stages of fvFTD show no significant loss of volume in any frontal lobe area as measured by a novel MRI volumetric technique. When volume loss does occur, changes are initially seen in the orbitofrontal cortex before atrophy becomes more widespread. These results provide some partial support for the often-quoted assumption that the orbitofrontal cortex is the locus of earliest pathology in fvFTD, although these findings must be regarded as preliminary in view of the small numbers of patients involved.