Increased pulse pressure associated with age-related arterial stiffening increases risk for Alzheimer dementia but the mechanism responsible for this association remains unclear.OBJECTIVES To determine the relationship between pulse pressure and cerebral spinal fluid biomarker profiles of preclinical Alzheimer disease, investigate whether observed relationships are stronger in adults with more advanced arterial age (Ն80 years of age), and examine the relationship between pulse pressure and progression to dementia. DESIGN, SETTING, AND PARTICIPANTSIn this retrospective cohort study, 877 participants without dementia (55-91 years of age) from the Alzheimer's Disease Neuroimaging Initiative underwent baseline health assessment, including blood pressure assessment and lumbar puncture for determination of cerebral spinal fluid phosphorylated tau (P-tau) and β-amyloid 1-42. Participants have been followed up longitudinally since 2005. The last date of examination was October 15, 2013. Clinical follow-up between 6 and 96 months tracked progression to dementia. MAIN OUTCOMES AND MEASURESRegression and analysis of covariance analyses investigated relationships between pulse pressure and distinct cerebral spinal fluid biomarker profiles. Very old participants (80 years or older) were compared with younger participants (55-79 years of age) on clinical measures and pulse pressure × age group interactions were investigated. Survival analysis examined the effect of baseline pulse pressure on progression to dementia. Covariates were age, sex, apolipoprotein E genotype, body mass index, vascular risk factors, and antihypertensive medication use.RESULTS Individuals with a P-tau-positive biomarker profile exhibited mean (SD) elevated pulse pressure regardless of age (62.0 [15.6] mm Hg for a P-tau-positive biomarker vs 57.4 [14.0] mm Hg for P-tau-negative biomarker; P = .04). In very old participants, a further increase in pulse pressure was observed in those exhibiting both P-tau elevation and β-amyloid 1-42 reduction vs either biomarkers alone (69.7 [16.0] mm Hg for both positive biomarkers vs 63.18 [13.0] mm Hg for P-tau alone vs 60.1 [16.4] mm Hg for β-amyloid 1-42 alone vs 56.6 [14.5] mm Hg for negative biomarkers; P = .003). Those with higher baseline pulse pressure progressed to dementia more rapidly (95% CI, 1.000-1.048; P = .05; hazard ratio = 1.024). Systolic pressure exhibited similar relationships with Alzheimer disease biomarkers and progression to dementia in the very old subgroup (P < .05) but showed no associations in the young old subgroup (P > .10). Diastolic pressure was reduced in young old participants with isolated phosphorylated tau elevation (P = .04). CONCLUSIONS AND RELEVANCEPulse pressure, an index of vascular aging, was associated with neurodegenerative change prior to the onset of dementia across a broad age range. Among those with more advanced age, higher pulse pressure was also associated with cerebral amyloidosis in the presence of neurodegeneration and more rapid progression to dementia. Diastolic ...

Background: Hallucinations occur in 20-40% of PD patients and have been associated with unfavorable clinical outcomes (i.e., nursing home placement, increased mortality). Hallucinations, like other non-motor features of PD, are not well recognized in routine primary/secondary clinical practice. So far, there has been no instrument for uniform characterization of hallucinations in PD. To this end, we developed the University of Miami Parkinson's disease Hallucinations Questionnaire (UM-PDHQ) that allows comprehensive assessment of hallucinations in clinical or research settings.

Objective To examine the distributions of proton magnetic resonance spectroscopy (MRS) observed metabolites in Parkinson’s Disease (PD) throughout the brain. Methods Twelve well-characterized PD patients and 18 age-matched controls were studied using MRI and volumetric MR Spectroscopic Imaging. Average values of signal normalized metabolite values for N-acetyl-aspartate, total-creatine, and total-choline (NAA, Cre, Cho, respectively) and their ratios were calculated for grey- (GM) and white-matter (WM) in each lobar brain region. PD participants also underwent comprehensive neuropsychological testing. Results Analyses revealed altered metabolite values in PD subjects relative to controls within the GM of the temporal lobe (Right: elevated Cre, p=.027; decreased NAA/Cre, p=.019; decreased Cho/Cre, p=.001 and Left: decreased NAA/Cre; p=.001, decreased Cho/Cre, p=.007); the right occipital lobe (decreased NAA, p=.032 and NAA/Cre, p=.016); and the total cerebrum GM (decreased NAA/Cre, p=.029). No meaningful correlations were obtained between abnormal metabolite values and the neuropsychological measures. Conclusions This study indicates that PD is associated with widespread alterations of brain metabolite concentrations, with a primary finding of increased creatine. It is hypothesized that higher creatine values in our PD sample may reflect greater neuronal energy expenditure early in the disease process that are compensatory. This is the first MRS study of PD that has examined metabolite changes across a large fraction of the brain volume, including the cortical mantle. Further work is needed to define the changes that take place in brain metabolites as PD progresses and their relationship to cognition and motor function.

OSA severity and presence of self-reported hypertension are associated with poor auditory verbal memory and executive function in older adults.

Atrophy of the hippocampus and surrounding temporal regions occurs in Alzheimer’s disease (AD). APOE ε4, the major genetic risk factor for late-onset AD, has been associated with smaller volume in these regions before amyloidosis can be detected by AD biomarkers. To examine APOE ε4 effects in relation to aging, we performed a longitudinal MRI study involving cognitively normal adults (25 APOE ε4 carriers and 31 ε3 homozygotes), initially aged 51–75 years. We used growth curve analyses, which can provide information about APOE ε4-related differences initially and later in life. Hippocampal volume was the primary outcome; nearby medial temporal regions were secondary outcomes. BDNF val66met was a secondary covariate. APOE ε4 carriers had significantly smaller initial hippocampal volumes than ε3 homozygotes. Rate of hippocampal atrophy was not greater in the APOE ε4 group, even though age-related atrophy was detected in the overall sample. The findings add to the growing evidence that effects of APOE ε4 on hippocampal size begin early in life, underscoring the importance of early interventions to increase reserve.