In hypertension (HTN), cerebral blood flow (CBF) regulation limits are changed and the blood pressure (BP) threshold at which CBF is safely maintained is higher. This shift may increase the brain's vulnerability to hypoperfusion at lower BP. Despite growing recognition of the link between hypoperfusion and neurodegeneration little is known about whether blood pressure reductions can induce deficient perfusion and promote expression of cerebrospinal fluid (CSF) biomarkers of amyloid and neurofibrillary pathology. We investigated the relationship between longitudinal changes in mean arterial pressure (MAP) and CSF biomarkers of Alzheimer's disease in a group of cognitively healthy elderly with and without HTN. Longitudinal assessments of blood pressure (MAP), CSF p-tau181 (phosphorylated tau), total tau, amyloid ß 1-42 (Aß42), cognition and whole brain volume were conducted on average 2.0±0.6 years apart in a group of 77 cognitively healthy elderly (age 63.4±9.4, range 44-86 years; education 16.9±2.1, range 10-22 years; 60% women). MAP was calculated as: 1/3 systolic blood pressure + 2/3 of diastolic blood pressure. At baseline HTN was found in 23 individuals (30%). When longitudinal change (ˆ†) in p-tau181 was predicted with the ˆ†MAP, HTN, and the HTNxˆ†MAP interaction, both the total model (F 3,73=3.9, p=.01), and the interaction term (p=.01) were significant. These data indicate that the relationship between ˆ†MAP and ˆ†p-tau181 was strongly dependent on the presence or absence of HTN. Only in the HTN group was a decrease in MAP from baseline to follow-up related to an increase in p-tau181 (r=-0.5, p=.01). In addition, only among subjects with HTN, was a reduction in MAP related to the worsening of verbal episodic memory (r=0.46, p=.03). Finally in the entire group the increase in p-tau181 was associated with reduction in the verbal episodic memory score (ß=-.223, p=.048). No relationship was observed between changes in MAP and whole brain volume. In subjects with HTN, MAP reduction is associated with increased CSF p-tau181 and deterioration of episodic memory, possibly resulting from suboptimal perfusion and subsequent accumulation of neurofibrillary tangles. Prior experimental work has demonstrated a relationship between perfusion, energetic reductions and tauopathy.
Little is known of combined utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers for prediction of Alzheimer's disease (AD) and longitudinal data is scarce. We examined these biomarkers at baseline and longitudinally in incipient AD. Forty-five subjects [21 controls (NL-NL), 16 stable MCI (MCI-MCI), 8 MCI who declined to AD (MCI-AD)] received MRI and lumbar puncture at baseline and after 2 years. CSF measures included total and phosphorylated tau (T-tau, P-tau(231)), amyloid-beta (Abeta(42)/Abeta(40)) and isoprostane. Voxel-based morphometry identified gray matter concentration (GMC) differences best distinguishing study groups and individual GMC values were calculated. Rate of medial temporal lobe (MTL) atrophy was examined using regional boundary shift (rBS) method. At baseline, for MRI, MCI-AD showed reduced GMC-MTL, and for CSF higher CSF T-tau, P-tau(231), IP and lower Abeta(42)/Abeta(40) as compared with MCI-MCI or NL-NL. Longitudinally, rBS-MTL atrophy was higher in MCI-AD than in either MCI-MCI or NL-NL, particularly in the left hemisphere. CSF data showed longitudinally greater increases of isoprostane in MCI-AD as compared with NL-NL. Combining baseline CSF-P-tau(231) and GMC-MTL significantly increased overall prediction of AD from 74% to 84% (p(step)<0.05). These results provide support for including multiple modalities of biomarkers in the identification of memory clinic patients at increased risk for dementia.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChelation of uranyl ions by adenine nucleotides. III. Further nuclear magnetic resonance investigation of the uranyl nitrate-adenosine 5'-monophosphate system at basic pH (7.5-11.4)Isaac Feldman and Kenneth E. RichCite this: J. Am. Chem. Soc. 1970, 92, 15, 4559–4564Publication Date (Print):July 1, 1970Publication History Published online1 May 2002Published inissue 1 July 1970https://pubs.acs.org/doi/10.1021/ja00718a014https://doi.org/10.1021/ja00718a014research-articleACS PublicationsRequest reuse permissionsArticle Views46Altmetric-Citations18LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Not all studies confirm that subjective memory complaints (SMCs), in otherwise healthy elderly subjects, are predictive of future cognitive decline. Our goal was to examine whether the probability of decline increases with the increasing severity of SMCs. 150 healthy subjects over the age of 50 (67% female) were included in a longitudinal study; mean follow–up time was 6.6 years (SD 3.9), mean number of visits 4. At baseline all subjects underwent medical and cognitive examinations: GDS (Global Deterioration Scale) staging, MMSE, memory (delayed paragraph recall), attention and concentration (digit backward test), executive functions (digit symbol substitution test), depression (Hamilton Depression Rating Scale), and severity of subjective memory complaints (MAC–Q). The clinical outcome was based on the last visit for every participant, and determined by repeated clinical and cognitive examinations. Three outcome groups were created: non–decliners, decliners and subjects diagnostically unstable with diagnosis changing over time (i.e. normal to mild cognitive impairment to normal). At baseline, 127 subjects were classified as having SMCs (GDS 2) and 23 without complaints (GDS 1). The GDS1 group was younger (64 vs. 68), had higher MMSE scores (29.6 vs 28.9) and lower MACQ scores (0.6 vs. 4.7). At follow–up the proportion of non–decliners was significantly higher in the GDS1 than GDS2 group (69% vs. 37%, chi2=8.4), p<.05). Based on the severity of complaint, age and severity of depressive symptoms, discriminant function analyses successfully predicted 84.6% of the unstable, 63.6% of declining and 49% of the non–declining group. Overall 60.3% of the original group was correctly classified. Membership in the declining group was poorly predicted by the severity of SMCs. However, the unstable group at follow–up was associated with younger age, more depressive symptoms, and more severe SMCs at baseline. The lack of SMCs is associated with a good outcome, but once there are subjective complaints, a greater severity does not indicate greater risk of decline. Rather, more severe SMCs are characteristic for the diagnostically unstable group. Together with higher depressive symptoms and younger age, severe SMCs may designate a subgroup that should be observed with caution to avoid possible misdiagnoses.
