Reduced retention of Pittsburgh compound B in white matter lesions.

PURPOSE: One of the interesting features of the amyloid tracer Pittsburgh compound B (PiB) is that it generates a signal in the white matter (WM) in both healthy subjects and cognitively impaired individuals. This characteristic gave rise to the possibility that PiB could be used to trace WM pathology. In a group of cognitively healthy elderly we examined PiB retention in normal-appearing WM (NAWM) and WM lesions (WML), one of the most common brain pathologies in aging. METHODS: We segmented WML and NAWM on fluid attenuation inversion recovery (FLAIR) images of 73 subjects (age 61.9 ± 10.0, 71 % women). PiB PET images were corrected for partial volume effects and coregistered to FLAIR images and WM masks. WML and NAWM PiB signals were then extracted. RESULTS: PiB retention in WML was lower than in NAWM (p < 0.001, 14.6 % reduction). This was true both for periventricular WML (p < 0.001, 17.8 % reduction) and deep WML (p = 0.001, 7.5 % reduction). CONCLUSION: PiB binding in WM is influenced by the presence of WML, which lower the signal. Our findings add to the growing evidence that PiB can depict WM pathology and should prompt further investigations into PiB binding targets in WM.

Nutrient intake and brain biomarkers of Alzheimer's disease in at-risk cognitively normal individuals: a cross-sectional neuroimaging pilot study.

OBJECTIVE: There is increasing evidence to suggest that diet, one of the most important modifiable environmental factors, may play a role in preventing or delaying cognitive decline and Alzheimer's disease (AD). This study examines the relationship between dietary nutrients and brain biomarkers of AD in cognitively normal individuals (NL) with and without AD risk factors. DESIGN: As part of an ongoing brain imaging study, participants received clinical and laboratory examinations, a neurocognitive test battery, positron emission tomography (PET) with (11)C-Pittsburgh Compound-B (PiB; a measure of amyloid-ß (Aß) load) and (18)F-fluorodeoxyglucose (FDG; a proxy of neuronal activity), and completed semiquantitative food frequency questionnaires. SETTING: Research centre affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. PARTICIPANTS: 49 NL individuals (age 25-72 years, 69% women) with dietary information, (11)C-PiB and (18)F-FDG PET scans were examined. RESULTS: Controlling for age and total caloric intake, higher intake of vitamin B12, vitamin D and ω-3 polyunsaturated fatty acid (PUFA) was associated with lower Aß load in AD regions on PiB-PET, while higher intake of ß-carotene and folate was associated with higher glucose metabolism on FDG-PET. ß-carotene and folate were associated with reduced glucose metabolism for women, apolipoprotein E epsilon 4 (APOE4) carriers and participants with positive AD family history, but not for their risk-free counterparts. The associations of vitamin B12, vitamin D and ω-3 PUFA with PiB retention were independent of gender, APOE and family history. The identified nutrient combination was associated with higher intake of vegetables, fruit, whole grains, fish and legumes, and lower intake of high-fat dairies, meat and sweets. CONCLUSIONS: Our data provide a potential pathophysiological mechanism for epidemiological findings showing that dietary interventions may play a role in the prevention of AD. Longitudinal studies are needed to determine whether there is a direct link between nutrient intake, brain biomarkers and risk of AD.

Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD.

OBJECTIVES: This brain imaging study examines whether cognitively normal (NL) individuals with 2 parents affected by late-onset Alzheimer disease (LOAD) show evidence of more extensive Alzheimer disease pathology compared with those who have a single parent affected by LOAD. METHODS: Fifty-two NL individuals received MRI, (11)C-Pittsburgh compound B (PiB)-PET, and (18)F-fluoro-2-deoxyglucose (FDG)-PET. These included 4 demographically balanced groups (n = 13/group, aged 32-72 years, 60% female, 30% APOE ε4 carriers) of NL individuals with maternal (FHm), paternal (FHp), and maternal and paternal (FHmp) family history of LOAD, and with negative family history (FH-). Statistical parametric mapping, voxel-based morphometry, and z-score mapping were used to compare MRI gray matter volumes (GMVs), partial volume-corrected PiB retention, and FDG metabolism across FH groups and vs FH-. RESULTS: NL FHmp showed more severe abnormalities in all 3 biomarkers vs the other groups regarding the number of regions affected and magnitude of impairment. PiB retention and hypometabolism were most pronounced in FHmp, intermediate in FHm, and lowest in FHp and FH-. GMV reductions were highest in FHmp and intermediate in FHm and FHp vs FH-. In all FH+ groups, amyloid-ß deposition exceeded GMV loss and hypometabolism exceeded GMV loss (p < 0.001), while amyloid-ß deposition exceeded hypometabolism in FHmp and FHp but not in FHm. CONCLUSIONS: These biomarker findings show a "LOAD parent-dose effect" in NL individuals several years, if not decades, before possible clinical symptoms.

Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals.

Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Aß-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Aß-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Aß-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Aß-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimer's disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.

Reduction in lateral thermal damage using heat-conducting templates: a comparison of continuous wave and pulsed CO2 lasers.

BACKGROUND AND OBJECTIVES: The advantages of the continuous wave (c.w.) CO(2) laser are offset by the delay in laser wound healing secondary to thermal damage. We have developed novel heat-conducting templates to reduce laser thermal damage. Because shortened pulse durations also decrease thermal damage, we tested the effectiveness of heat-conducting templates with a c.w. CO(2) clinical laser and a short-pulsed CO(2) laser to determine the best method and mechanism to minimize thermal damage. STUDY DESIGN/MATERIALS AND METHODS: Comparison of 0.2-second shuttered c.w. and 5-microsecond pulsed CO(2) lasers were made by doing incisions on 150 tissue samples from reduction mammoplasties and abdominoplasties. Copper, aluminum, glass, and Plexiglass heat-conducting templates were tested against no template (air) with both lasers. Histological samples were evaluated using computerized morphometrics analysis. RESULTS: Statistically significant reductions in lateral thermal damage were seen with the copper (50%) and aluminum (39%) templates used with the c.w. CO(2) laser. Only the copper template (39%) significantly reduced thermal damage when used with the pulsed CO(2) laser. Less thermal damage was seen using the pulsed CO(2) laser compared to the c.w. CO(2) laser with each template. CONCLUSIONS: Heat-conducting templates significantly reduced the amount of lateral thermal damage when used with the c.w. CO(2) laser (copper and aluminum) and short-pulsed CO(2) laser (copper). The c.w. CO(2) laser with the copper template compared favorably to the short-pulsed CO(2) laser without a template. Therefore, both heat conductive templates and short-pulse structure provide successful methods for reducing lateral thermal damage, and a combination of the two appears to provide optimal results.

Free-electron laser and heat-conducting templates: a study of reducing cutaneous lateral thermal damage.

BACKGROUND AND OBJECTIVES: We developed novel heat-conducting templates, and tested whether they could effectively remove damaging heat from the tissue during laser ablation. The reduction of lateral thermal damage during cutaneous incisional laser procedures should decrease the time in wound healing. In addition, we selected various infrared wavelengths to determine whether the template effects would be influenced by the laser penetration depth and the particular chromophore absorbing the laser light. STUDY DESIGN/MATERIALS AND METHODS: This study utilized the Free-Electron Laser at wavelengths of 3.0, 5.5, 6.45, 7.5, and 7.7 microm to produce 1.0 cm incisions on in vitro lightly pigmented human skin. At each of these wavelengths, copper, aluminum, glass, and Plexiglas heat conducting templates were tested. At wavelength 5.5 microm, the study was duplicated using in vitro darkly pigmented skin. Histological samples were evaluated using computerized morphometric analysis. RESULTS: The adjunct use of both the copper and aluminum templates provided a decrease in thermal damage at each wavelength. Using the copper template reduced lateral thermal damage an average of 67% with no apparent wavelength dependence. The aluminum template reduced thermal damage an average of 54% with no apparent wavelength dependence. The glass and Plexiglas templates did not reduce the lateral thermal damage. At 5.5 microm, no statistically significant difference in lateral thermal damage was observed between darkly and lightly pigmented tissues. CONCLUSIONS: Heat-conducting templates are an effective new method to reduce lateral thermal damage from thermal laser incisions.