Toward personalized cognitive diagnostics of at-genetic-risk Alzheimer’s disease

Toward personalized cognitive diagnostics of at-genetic-risk Alzheimer’s disease

Potential use of Big Data mined from a VR game for preclinical diagnostics…

Source: https://www.pnas.org/content/116/19/9285

Significance

We report that assessment of navigational behavior using the Sea Hero Quest app provides a means of discriminating healthy aging from genetically at-risk individuals of Alzheimer’s disease (AD). It further highlights that the global Sea Hero Quest database can be employed as a normative benchmark dataset to efficiently determine the significance of spatial abnormality suspected to be indicative of incipient AD on an individual level.

Abstract

Spatial navigation is emerging as a critical factor in identifying preclinical Alzheimer’s disease (AD). However, the impact of interindividual navigation ability and demographic risk factors (e.g., APOE, age, and sex) on spatial navigation make it difficult to identify persons “at high risk” of AD in the preclinical stages. In the current study, we use spatial navigation big data (n = 27,108) from the Sea Hero Quest (SHQ) game to overcome these challenges by investigating whether big data can be used to benchmark a highly phenotyped healthy aging laboratory cohort into high- vs. low-risk persons based on their genetic (APOE) and demographic (sex, age, and educational attainment) risk factors. Our results replicate previous findings in APOE ε4 carriers, indicative of grid cell coding errors in the entorhinal cortex, the initial brain region affected by AD pathophysiology. We also show that although baseline navigation ability differs between men and women, sex does not interact with the APOE genotype to influence the manifestation of AD-related spatial disturbance. Most importantly, we demonstrate that such high-risk preclinical cases can be reliably distinguished from low-risk participants using big-data spatial navigation benchmarks. By contrast, participants were undistinguishable on neuropsychological episodic memory tests. Taken together, we present evidence to suggest that, in the future, SHQ normative benchmark data can be used to more accurately classify spatial impairments in at-high-risk of AD healthy participants at a more individual level, therefore providing the steppingstone for individualized diagnostics and outcome measures of cognitive symptoms in preclinical AD.

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Whole-Body Cryotherapy a Hot New Treatment for Depression?

Whole-Body Cryotherapy a Hot New Treatment for Depression?

Liam Davenport

April 11, 2019

WARSAW, Poland — Adjunctive whole-body cryotherapy may convey added benefit in patients with depressive disorders, new research suggests.

This type of therapy, which involves subjecting the body to extremely low temperatures for short periods of time, is already used in rheumatoid and neurologic conditions, as well as for biological rejuvenation in athletes.

There is also a small, but growing, body of evidence that the technique may be used in mood disorders, potentially through the modulation of inflammatory or immunologic markers.

In the current randomized study of more than 50 patients already receiving treatment for depression, those exposed to “true cryotherapy” once daily for 10 days experienced significant improvements in depression scores and in measures of motivation, mood, and sleep quality compared with those exposed to low but non-cryotherapy temperatures.

These early results “are very promising and we think [cryotherapy] is worth further exploration” as an adjuvant treatment in depression, said Julia Rymaszewska, a student in the Psychiatry Department at Wrocław Medical University, Poland.

She presented the findings here at the European Psychiatric Association (EPA) 2019 Congress.

To test the use of cryotherapy in depression, the investigators initially assessed 117 patients with depressive disorder already receiving standard psychopharmacology therapy.

From these, 56 patients were randomly assigned to an experimental group
(n = 30) or a control group (n = 26).

Both groups underwent 2- to 3-minute sessions of whole-body cryotherapy once a day for 10 days. The experimental group was exposed to a true cryotherapy temperature of -110°C to -160°C (-166°F to -256°F), while the control group experienced a sham protocol with a temperature of -50°C (-58°F).

The participants completed the Beck Depression Inventory (BDI) and a visual analog scale assessing level of motivation, mood, and sleep quality before, during, and after the treatment period.

Patients who experienced true whole-body cryotherapy showed significant improvements on the BDI compared with the control group, who had relatively stable scores.

In particular, patients in the experimental group showed significant reductions in scores on both the cognitive-affective (P = .000) and the somatic (P = .028) BDI subscales.

Patients in the experimental group also reported significant increases in scores on the visual analog scale compared with those in the control group (P = .035), albeit with both groups showing improvements over the course of the study.

Feasible? Cost Effective?

Jessica Bone, a PhD candidate in the Division of Psychiatry, University College London, UK, chaired the poster presentation. She described the study as “intriguing” but was unsure as to the principle of how cryotherapy would work in depression.

“I would like to hear a bit more about the overall findings from the trial and see the results presented again in more detail,” she told Medscape Medical News.

Bone also expressed doubts over the cost effectiveness and feasibility of cryotherapy in this setting, wondering “therefore how practical it would be on a clinical level.”

Nevertheless, she said that the potential link with the inflammatory therapy of depression is “very interesting” and that “there is a lot more research to be done in that area.”

The study was supported by the Polish Ministry of Science and Higher Education. The study authors and Bone have disclosed no relevant financial relationships.

European Psychiatric Association (EPA) 2019 Congress: Poster EPA19-2584. Presented April 8, 2019.

May just Finnish sauna?

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Use of vitamin D drops leading to kidney failure in a 54-year-old man

Vitamin D supplementation plus sunbathing.

Use of vitamin D drops leading to kidney failure in a 54-year-old man

Bourne L. Auguste, Carmen Avila-Casado and Joanne M. Bargman
KEY POINTS

  • Vitamin D toxicity is rare, but clinicians must be aware of the risks of vitamin D use to limit complications related to hypercalcemia.

  • Calcium levels may get worse before getting better in patients even after cessation of supplements, as vitamin D is fat soluble.

  • Observational data and expert opinion suggest that glucocorticoids, ketoconazole and hydroxychloroquine are reasonable options to treat hypercalcemia related to vitamin D toxicity by decreasing the “active” 1, 25 dihydroxyvitamin D3 levels.

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Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease

Original research article

Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease

 

  1. Ralph Kwame Akyea,
  2. Joe Kai,
  3. Nadeem Qureshi,
  4. Barbara Iyen,
  5. Stephen F Weng

Author affiliations

Abstract

Objective To assess low-density lipoprotein cholesterol (LDL-C) response in patients after initiation of statins, and future risk of cardiovascular disease (CVD).

Methods Prospective cohort study of 165 411 primary care patients, from the UK Clinical Practice Research Datalink, who were free of CVD before statin initiation, and had at least one pre-treatment LDL-C within 12 months before, and one post-treatment LDL-C within 24 months after, statin initiation. Based on current national guidelines, <40% reduction in baseline LDL-C within 24 months was classified as a sub-optimal statin response. Cox proportional regression and competing-risks survival regression models were used to determine adjusted hazard ratios (HRs) and sub-HRs for incident CVD outcomes for LDL-C response to statins.

Results 84 609 (51.2%) patients had a sub-optimal LDL-C response to initiated statin therapy within 24 months. During 1 077 299 person-years of follow-up (median follow-up 6.2 years), there were 22 798 CVD events (12 142 in sub-optimal responders and 10 656 in optimal responders). In sub-optimal responders, compared with optimal responders, the HR for incident CVD was 1.17 (95% CI 1.13 to 1.20) and 1.22 (95% CI 1.19 to 1.25) after adjusting for age and baseline untreated LDL-C. Considering competing risks resulted in lower but similar sub-HRs for both unadjusted (1.13, 95% CI 1.10 to 1.16) and adjusted (1.19, 95% CI 1.16 to 1.23) cumulative incidence function of CVD.

Conclusions Optimal lowering of LDL-C is not achieved within 2 years in over half of patients in the general population initiated on statin therapy, and these patients will experience significantly increased risk of future CVD.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline

Which means in plain English, perhaps some forms of TMS might reverse age-related (and pathological?) memory decline. Worth studying, for sure.

Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline

Aneesha S. Nilakantan, M.-Marsel Mesulam, Sandra Weintraub, Erica L. Karp, Stephen VanHaerents, Joel L. Voss

Abstract

Objective To test whether targeting hippocampal-cortical brain networks with high-frequency transcranial magnetic stimulation in older adults influences behavioral and neural measures characteristic of age-related memory impairment.

Methods Fifteen adults aged 64 to 80 years (mean = 72 years) completed a single-blind, sham-controlled experiment. Stimulation targets in parietal cortex were determined based on fMRI connectivity with the hippocampus. Recollection and recognition memory were assessed after 5 consecutive daily sessions of full-intensity stimulation vs low-intensity sham stimulation using a within-subjects crossover design. Neural correlates of recollection and recognition memory formation were obtained via fMRI, measured within the targeted hippocampal-cortical network vs a control frontal-parietal network. These outcomes were measured approximately 24 hours after the final stimulation session.

Results Recollection was specifically impaired in older adults compared to a young-adult control sample at baseline. Relative to sham, stimulation improved recollection to a greater extent than recognition. Stimulation increased recollection fMRI signals throughout the hippocampal-cortical network, including at the targeted location of the hippocampus. Effects of stimulation on fMRI recollection signals were greater than those for recognition and were greater in the targeted network compared to the control network.

Conclusions Age-related recollection impairments were causally related to hippocampal-cortical network function in older adults. Stimulation selectively modified neural and behavioral hallmarks of age-related memory impairment, indicating effective engagement of memory intervention targets in older adults.

  • Received September 12, 2018.
  • Accepted in final form January 17, 2019.

Source: https://n.neurology.org/content/early/2019/04/17/WNL.0000000000007502

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