Background 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 (AD) biomarkers, and the ApoE alleles. Methods 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 (Aβ42), as well as ApoE allele status. Findings 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/hypopnea with 4% O2-desaturation index (AHI4%) was positively correlated with P-Tau (r=0.30, p=0.023), T-Tau (r=0.31, p=0.021), and Aβ42 (r=0.31, p=0.021). In ApoE2+ subjects, AHI4% was correlated with lower levels of CSF Aβ42 (r=−0.71, p=0.004), similarly to ApoE4+ subjects where there was also a trend towards lower CSF Aβ42 levels Interpretation Our observations suggest that there is an association between SDB and CSF AD- biomarkers in cognitively normal elderly. Existing therapies for SDB such as CPAP could delay the onset to mild cognitive impairment or dementia in normal elderly.

Objectives Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer’s disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD. Design Cross-sectional study. Setting Manhattan (broader area). Participants Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-β, Aβ) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined. Measurements Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers. Results None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB&Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE&PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants&Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12&D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12&D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p<0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE&PUFA], and negatively associated with NP5 scores [Fats] (p<0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants&Fibers] (p<0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified ‘AD-protective’ nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter. Conclusion Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on Aβ and associated neuronal impairment.

This study demonstrates functional preservation and improved histological appearance of the injured glottis after a single treatment with topical mitomycin-C. Potential applications of these findings include prophylactic use of topical mitomycin-C on glottic insults that commonly progress from granulation tissue formation to scarring and decreased vocal fold function.

To develop a model for recurrent anterior glottic stenosis and to test the efficacy of topical mitomycin-C in preventing restenosis, we induced anterior glottic stenosis with a CO2 laser in 5 dogs. In 3 dogs, recurrence was established after surgical lysis. Subsequently, the 3 dogs received a single topical 3-minute treatment with a 1% solution of mitomycin-C after a second surgical lysis. In a parallel experiment, the other 2 dogs received a single topical 3-minute treatment with a 1% solution of mitomycin-C after the initial surgical lysis. An anterior glottic web was induced in all 5 dogs with the CO2 laser. The 3 dogs experienced restenosis at the anterior glottis after surgical lysis alone. Mitomycin-C prevented anterior glottic restenosis in 2 of the 3 dogs treated twice and in both of the dogs treated once (p = .02). We conclude that a recurrent stenosis of the anterior glottis may be induced reproducibly in the canine model with the CO2 laser. Application of topical mitomycin-C after lysis of an anterior glottic stenosis produces a statistically significant reduction in the rate of restenosis as compared to surgical lysis alone.

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 5 13/group, aged 32-72 years, 60% female, 30% APOE e4 carriers) of NL individuals with maternal (FHm), paternal (FHp), and maternal and paternal (FHmp) family history of LOAD, and with negative family history (FH2). Statistical parametric mapping, voxel-based morphometry, and z-score mapping were used to compare MRI gray matter volumes (GMVs), partial volumecorrected PiB retention, and FDG metabolism across FH groups and vs FH2. Alzheimer disease (AD) is an age-related neurodegenerative disease and the most common form of dementia. Clinical studies indicate that by the time patients seek diagnosis, the amount of irreversible brain damage that may have already occurred hinders treatment potential. Effective interventions, as they become available, ideally would be implemented in at-risk individuals before symptoms occur.Having a family history (FH) of AD is a major risk factor for developing the disease. 1,2 While the rare early-onset forms of AD (EOAD) have autosomal dominant genetic inheritance, the risk of developing late-onset AD (LOAD) (i.e., .99% of the AD population older than 60 years) is influenced by genetic and nongenetic factors.1 Although LOAD does not show recognizable mendelian inheritance, risk is to some extent genetically determined, as shown by the familial aggregation of many cases.2 Among probands, those with a parent affected by LOAD are at particularly high risk, 3,4 and the risk is higher still when both parents are affected. [5][6][7] However, because only ,5% of individuals have both parents affected by LOAD, 2,5-7 the clinical profile associated with this rare circumstance has been poorly studied and epidemiologic findings have not been characterized by the use of biomarkers.

ObjectiveThere 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.DesignAs part of an ongoing brain imaging study, participants received clinical and laboratory examinations, a neurocognitive test battery, positron emission tomography (PET) with 11C-Pittsburgh Compound-B (PiB; a measure of amyloid-β (Aβ) load) and 18F-fluorodeoxyglucose (FDG; a proxy of neuronal activity), and completed semiquantitative food frequency questionnaires.SettingResearch centre affiliated with the Alzheimer's disease Core Center at New York University School of Medicine.Participants49 NL individuals (age 25–72 years, 69% women) with dietary information, 11C-PiB and 18F-FDG PET scans were examined.ResultsControlling for age and total caloric intake, higher intake of vitamin B12, vitamin D and ω-3 polyunsaturated fatty acid (PUFA) was associated with lower Aβ load in AD regions on PiB-PET, while higher intake of β-carotene and folate was associated with higher glucose metabolism on FDG-PET. β-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.ConclusionsOur 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.

Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDGPET) in connected GM. WML masks from 72 cognitively normal (age 61.7±9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r=0.20, p<0.05 corrected) and lower PiB uptake (r=0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (β=0.045) and FDG-PET (β=0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition.

Purpose One of the interesting features of 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 can be used to trace WM pathology. In a group of cognitively healthy elderly, we examined PiB retention in normal-appearing WM (NAWM) and white matter lesions (WML), one of the most common brain pathologies in aging. Methods We segmented WML and NAWM from fluid attenuation inversion recovery (FLAIR) images of 73 subjects (age 61.9±10.0, 71% women). PET-PiB 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 within WML was lower than in NAWM (p<.001, 14.6% reduction). This was true both for periventricular WML (p<.001, 17.8% reduction) and deep WML (p=.001, 7.5% reduction). Conclusions 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 prompt further investigations into PiB binding targets in WM.