Hyperbaric Oxygen Medication for Alzheimer’s

Hyperbaric Oxygen Medication for Alzheimer’s

Alzheimers Dement (N Y). 2020; 6(1): e12030.

Jianwen Chen,
1
Feng Zhang,
2
,

3
Li Zhao,
1
Cheng Cheng,
2
,

3
Rujia Zhong,
2
,

3
Chunbo Dong,corresponding author
1
and Weidong Lecorresponding author
2
,

3

Summary

Introduction

It has been reported that environmental components equivalent to hypoxia would possibly possibly well furthermore make contributions to the pathogenesis of Alzheimer’s disease (AD). Therapeutics like hyperbaric oxygen medication, which improves tissue oxygen present and ameliorates hypoxic cases in the brain, would possibly possibly well furthermore be an different therapy for AD and amnestic soft cognitive impairment (aMCI). The showcase work aims to compare the aptitude therapeutic build of hyperbaric oxygen medication for AD and aMCI.

Methods

We recruited 42 AD, 11 aMCI, and 30 control AD patients in this survey. AD and aMCI patients had been treated with 40 minutes of hyperbaric oxygen once a day for 20 days and assessed by neuropsychiatric assessments including Mini‐Psychological Divulge Examination (MMSE), Montreal Cognitive Review (MoCA), and Activities of Each day Residing (ADL) scale sooner than and at 1‐, 3‐, and 6‐month prepare‐up after medication. Administration AD patients who had been not given hyperbaric oxygen medication had same medical profile as hyperbaric oxygen treated AD. We examined 10 of the AD/aMCI patients with fluorodeoxyglucose positron emission tomography.

Outcomes

In self‐comparison survey, one course of hyperbaric oxygen medication tremendously improved the cognitive aim assessed by MMSE and MoCA in AD patients after 1‐month prepare‐up; such medication also tremendously improved MMSE ranking at 3‐month prepare‐up and MoCA ranking at 1‐ and 3‐month prepare‐up in aMCI patients. The ADL scale modified into once tremendously improved in AD patients after 1‐ and 3‐month prepare‐up. As in contrast with the control AD patients, the MMSE and MoCA in hyperbaric oxygen treated AD patients had been tremendously improved after 1‐month prepare‐up. Hyperbaric oxygen medication also ameliorated the diminished brain glucose metabolism in about a of the AD and aMCI patients.

Conclusion

Primarily primarily primarily based on old stories and our recent findings, we recommend that hyperbaric oxygen medication would possibly possibly well furthermore be a promising different therapy for AD and aMCI.

Keywords: Alzheimer’s disease, hyperbaric oxygen medication, hypoxia, soft cognitive impairment

1. INTRODUCTION

Alzheimer’s disease (AD) is the most same outdated build of dementia in the elderly. It’s in most cases notion about that AD arises thru the interactions between genetic and non‐genetic components.
1
Genic components are dominantly inherited mutations in amyloid beta (Aβ) precursor protein, presenilin 1, and presenilin 2; and there are numerous threat genes, including apolipoprotein E, that would make contributions to the disease pathogenesis.
2
Non‐genetic components equivalent to brain trauma, cerebrovascular diseases, kind 2 diabetes, intellectual exercise, sleep problems, and hypoxia are notion to play a important aim in sporadic AD.
3
,
4
Outcomes from animal stories beget indicated that hypoxia affects many facets of AD‐connected pathophysiology including Aβ and tau neuropathy, neuroinflammation, autophagy dysfunction, oxidative stress, and mitochondrial abnormality.
5
,
6
,
7
,
8
In AD patients, comorbidities equivalent to stroke, cardiovascular diseases, obstructive sleep apnea syndrome, and chronic obstructive pulmonary disease (COPD) would possibly possibly well furthermore put off acute and chronic hypoxic cases.
8
,
9
,
10
A doable survey confirmed that girls with sleep‐disordered respiration had been likely to bear soft cognitive impairment or dementia.
11
Several stories beget reported that excessive‐altitude hypoxia exposure would possibly possibly well furthermore put off deleterious effects on cognitive performance.
12
,
13
Excessive altitude decreases brain oxygen saturation, reduces neural exercise, induces immune response, and impairs cognitive choices.
14
These evidences imply that hypoxia would possibly possibly well furthermore be a important perpetrator for cognitive decline. B hypoxia contributes to the pathogenesis of AD, anti‐hypoxia medication would possibly possibly well furthermore be priceless to ameliorate the disease. Hyperbaric oxygen medication is a smartly‐established therapy mature to treat neurological cases by improving oxygen shipping to brain tissues and give protection to neurons.
15
,
16

In step with the epidemiological records in 2005, 24.2 million folks worldwide suffer from dementia with 4.6 million fresh cases per yr. By 2040, there will more than likely be >81 million folks tormented by dementia, 70% of which are AD patients.
17
,
18
As the inhabitants ages, AD will definitely ship important social and economic burdens to the arena. Alternatively, there is unexcited no remedy or efficient medication to reverse the pathological task of AD. Currently there are easiest about a anti‐AD remedy in medical exercise, equivalent to cholinesterase inhibitors (ChEIs; donepezil, rivastigmine, and galantamine), and N‐Methyl‐D‐aspartic acid (NMDA) receptor antagonist (memantine). These remedy beget a restricted therapeutic build on indicators and poorly beget an affect on the event of the disease.
19
Despite worthy efforts to bear fresh anti‐AD remedy aiming to discontinue the event of AD, the therapeutic interventions predominantly focused on Aβ pathology beget restricted success.
20
Other unique therapeutics, including anti‐tau and anti‐irritation interventions beget not efficiently yielded any factual results.
19
,
21
Contemporary stories beget indicated that dementia and stroke half about a of the pathological threat components ensuing from cramped vessel degeneration; and dementia will more than likely be diminished thru stroke prevention by utilizing anticoagulation of atrial fibrillation and stop of smoking.
22
,
23
Microvascular circulation impairment ensuing in tissue hypoxia has been demonstrated in AD and amnestic soft cognitive impairment (aMCI), and the stage of hypoxia correlates with the extent of cognitive decline.
23
Furthermore, the hypoxia situation would possibly possibly well furthermore put off vitality failure ensuing in dyshomeostasis of cytosol calcium ion focus. The breakdown of the calcium ion signaling plan is one in every of the same outdated mechanisms of neurodegeneration.
23
Thus, hyperbaric oxygen medication, which improves tissue oxygen present and ameliorates hypoxic cases, would possibly possibly well furthermore be a doable therapeutic design for AD and aMCI.

Within the showcase survey, we recruited 42 AD and 11 aMCI patients for hyperbaric oxygen medication and 30 AD patients without hyperbaric oxygen medication as control. The total members had been examined with a battery of neuropsychiatric assessments sooner than and at 1‐, 3‐, and 6‐month prepare‐up after medication. We aimed to compare the aptitude therapeutic build of hyperbaric oxygen medication in patients with AD and aMCI.

2. METHODS

2.1. Patients

There beget been 42 AD and 11 aMCI patients enrolled in this hyperbaric oxygen survey. All members had been from the First Well being facility of Dalian Medical College for the length of 2015 to 2018. One other 30 AD patients who had same medical profile (age, intercourse, disease length, and history of remedy) but not enterprise hyperbaric oxygen medication had been recruited as control. The diagnosis of AD modified into once made in accordance with the components of the Diagnostic Statistical Manual of Psychological Disorders IV (DSM IV) and National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Illness and Related Disorders Association.
24
,
25
,
26
And the diagnosis of aMCI modified into once referred to the DSM IV and Petersen 2005 diagnostic criteria.
26
,
27
,
28
Patients with the following cases had been excluded: gait imbalance, extrapyramidal indicators, seizures, autonomic failures, severe psychiatric cases (main depression, psychosis, bipolar problems), poisonous exposure, cases which beget an affect on intelligence (severe anemia, thyroid disorder, and weight loss program B12 deficiency) and cases which beget an affect on brain oxygen metabolism (cerebral vascular ischemic disease, anemia, and un‐controlled hypertension and diabetes). In addition, the members had been dominated out with any of the following contraindications of hyperbaric oxygen medication: pneumothorax, rib atomize, chest trauma, cavitary pulmonary tuberculosis, resistant hypertension, severe pneumonia, bronchial asthma, pulmonary coronary heart disease, and COPD. AD and control patients in this survey had been contemporarily maintained with their medicines including memantine (20 mg/d) and/or rivastigmine (6 to 12 mg/d) on a frequent basis. Patients with aMCI had been not treated with any cognitive medicines.

The survey of hyperbaric oxygen medication in AD and aMCI modified into once accredited by the Ethics Committee of the First Affiliated Well being facility of Dalian Medical College sooner than the survey started. All enrolled patients and their correct guardians beget been informed of the survey map and the hazards that would possibly discontinue up from the medication, and they beget agreed and signed the informed consent.

The demographic traits of patients enrolled in this survey had been summarized in Desk S1 in supporting files. There beget been 42 AD patients (13 male/29 feminine). The imply age of AD patients modified into once 70.17 ± 8.95 years customary, and the imply disease course modified into once 4.14 ± 2.31 years. All patients carried out the 20‐day hyperbaric oxygen medication and 1‐ and 3‐month prepare‐up. Two of the AD patients had been dropped at the 6‐month prepare‐up: one died of heart problems, and the opposite one left the customary resident district and moved to any other city. There beget been 11 aMCI patients enrolled in this survey (7 male/4 feminine). The imply age of these patients modified into once 65.36 ± 9.50 years customary, and the imply disease course modified into once 1.73 ± 0.91 years. All 11 aMCI members carried out the total survey. There beget been 30 control AD (12 male/18 feminine). The imply age of these patients modified into once 69.87 ± 7.79 years customary, and the imply disease course modified into once 3.93 ± 2.60 years. There beget been no differences between hyperbaric oxygen treated AD and control AD in age, intercourse, age of onset, education stage, disease course, and Mini‐Psychological Divulge Examination (MMSE) and Montreal Cognitive Review (MoCA) rankings at baseline stage.

RESEARCH IN CONTEXT

  1. Systematic review: Hypoxia is one in every of the important environmental components that would possibly possibly well furthermore make contributions to the pathogenesis of Alzheimer’s disease (AD). Currently accredited drug therapies for AD beget a restricted therapeutic build on indicators and poorly beget an affect on the event of the disease. Non‐pharmacological multi‐centered interventions like hyperbaric oxygen medication focused on hypoxia would possibly possibly well furthermore beget doable in the long flee medication of AD.

  2. Interpretation: We recruited 42 AD and 11 amnestic soft cognitive impairment (aMCI) patients for hyperbaric oxygen medication and 30 AD patients without hyperbaric oxygen medication as control and performed a 6‐month prepare‐up survey. We stumbled on that hyperbaric oxygen medication would possibly possibly well furthermore give a enhance to cognitive choices and ameliorate the diminished brain glucose metabolism in AD and aMCI patients.

  3. Future instructions: Multi‐heart stories with better numbers of members with or without medicines, more than one courses of therapies, and longer time of prepare‐up will beget to unexcited be utilized in future stories.

2.2. Neuropsychiatric assessments

Neuropsychiatric assessments mature in the survey had been MMSE, MoCA, and Activities of Each day Residing (ADL) scale.
29
,
30
,
31
,
32
After the medical history series, physical examination, laboratory tests, and neuroimaging, the patients had been examined with the neuropsychiatric assessments sooner than the hyperbaric oxygen medication and re‐examined at 1‐, 3‐, and 6‐month prepare‐up. The MMSE assesses the cognitive choices of orientation, registration, attention and calculation, utilize, and language. The MoCA contains six sub‐devices of visuospatial skills and government choices, naming, reminiscence, attention and calculation, language and summary reasoning, and orientation to time and spot. The ADL scale evaluates independence of day to day actions (bathing, dressing, toileting, transferring, ingesting, and the utilization of incontinence materials) with 20 questions.

2.3. Hyperbaric oxygen medication

All 42 AD and 11 aMCI members undertook one course of hyperbaric oxygen medication once a day for 20 days. Every medication integrated 20‐minute pure oxygen inhalation (O2 = 99.9%, oxygen present strain 0.4 to 0.7 MPa, oxygen circulation 10 to 15 L/h), 15 minutes interval, and then any other 20‐minute pure oxygen inhalation (O2 = 99.9%, oxygen present strain 0.4 to 0.7 MPa, oxygen circulation 10 to 15 L/h) below the strain of 0.22 MPa (0.12 MPa on strain gauge) in hyperbaric oxygen chamber (Medical Oxygen Chamber, SY3200‐8500, Yantai Hongyuan Oxygen Industrial Inc., Shandong, China).

2.4. Fluorodeoxyglucose positron emission tomography

Six of the AD patients and four of the aMCI patients underwent fluorodeoxyglucose positron emission tomography (FDG‐P) sooner than and at 1 month after hyperbaric oxygen medication. The 18F‐FDG (radiochemical purity >95%) modified into once synthesized by the Eclipse RD cyclotron and the FDG synthesizer Explora FDG4 (Siemens AG, Germany). All patients fasted for not not as much as 6 hours, and the physique weight and serum glucose stage had been certain sooner than the injection. The fasting blood glucose <9 mmol/L modified into once acceptable. Then a dose of 0.15 mCi/kg of FDG modified into once injected by means of a peripheral cannula after resting for 30 to 40 minutes. After injection, the patients had been suggested to protect conscious, desire eyes initiate, and not vocalize in a soundless and darkened room for 40 minutes. The footage had been then received with Siemens Biograph 64 HD P/CT (Siemens AG, Germany). All photography had been when in contrast with the template and analyzed with NeuroQ™ Mind Imaging Diagnosis (Syntermed Inc., Atlanta, GA, USA).

2.5. Recordsdata diagnosis

Recordsdata had been analyzed by SPSS 21.0 tool (IBM Company, Armonk, NY, USA) and GraphPad Prism 8 (GraphPad Instrument Inc., La Jolla, CA, USA). The outcomes had been notion about to be statistically important when P mark modified into once <0.05.

3. RESULTS

3.1. Cognitive assessments of AD and aMCI patients sooner than and after hyperbaric oxygen medication

3.1.1. MMSE ranking sooner than and after medication

As in contrast with the baseline stage, the MMSE ranking modified into once tremendously improved at 1‐month prepare‐up in AD patients (Desk 1) and at 3‐month prepare‐up in aMCI patients after hyperbaric oxygen medication (Desk 1). As in contrast with control AD, the hyperbaric oxygen treated AD patients received important improvement in MMSE ranking at 1‐month prepare‐up.

TABLE 1

Self‐comparison of MMSE rankings in AD and aMCI patients sooner than and after hyperbaric oxygen medication

AD aMCI
Time Suggest ± SD P mark Suggest ± SD P mark
Baseline 15.19 ± 7.55 27.00 ± 2.19
1‐month prepare‐up 16.43 ± 8.21 0.005
28.00 ± 2.28 0.070
3‐month prepare‐up 15.38 ± 8.05 0.750 28.45 ± 1.97 0.026
6‐month prepare‐up 13.95 ± 7.63 0.056 27.82 ± 2.34 0.136

3.1.2. MoCA ranking sooner than and after medication

The MoCA ranking modified into once improved tremendously at 1‐month prepare‐up in AD patients and at 1‐month and 6‐month prepare‐up in aMCI patients after hyperbaric oxygen medication when in contrast to the baseline stage (Desk 2). The six subitems of MoCA rankings are summarized in Desk 2. The visuospatial skills and government choices had been tremendously improved at 1‐month prepare‐up and the language and summary reasoning had been tremendously improved at 1‐, 3‐, and 6‐month prepare‐up in AD patients after hyperbaric oxygen medication when in contrast to baseline stage (Desk 2). In aMCI patients, the language and summary reasoning had been improved at 1‐month prepare‐up after hyperbaric oxygen medication. Memory aim of aMCI patients modified into once ameliorated at 1‐, 3‐, and 6‐month prepare‐up after hyperbaric oxygen medication when in contrast to baseline stage (Desk 2). As in contrast with control AD, the hyperbaric oxygen treated AD patients received tremendously better MoCA ranking at 1‐month prepare‐up (Figure 1).

TABLE 2

Self‐comparison of MoCA rankings in AD and aMCI patients sooner than and after hyperbaric oxygen medication

AD aMCI
Baseline 1‐month prepare‐up 3‐month prepare‐up 6‐month prepare‐up Baseline 1‐month prepare‐up 3‐month prepare‐up 6‐month prepare‐up
MoCA rankings 10.86 ± 6.70 12.71 ± 7.39 11.38 ± 6.64 10.53 ± 6.69 21.91 ± 3.27 24.73 ± 4.31 24.64 ± 5.07 25.18 ± 4.24
P mark 0.000
0.280 0.799 0.007
0.059 0.019
Visuospatial skills and government choices 1.45 ± 1.43 1.74 ± 1.36 1.60 ± 1.42 1.65 ± 1.44 3.82 ± 0.87 4.00 ± 1.00 4.18 ± 0.98 4.36 ± 0.67
P mark 0.032
0.275 0.094 0.414 0.340 0.058
Naming 1.86 ± 1.14 2.00 ± 1.04 1.83 ± 1.15 1.75 ± 1.08 3.00 ± 0.00 3.00 ± 0.00 3.00 ± 0.00 2.91 ± 0.30
P mark 0.326 0.837 0.572 1.00 1.00 0.317
Memory 0.48 ± 1.17 0.64 ± 1.34 0.48 ± 1.23 0.50 ± 1.20 1.00 ± 1.26 2.82 ± 2.09 2.73 ± 2.24 2.73 ± 2.05
P mark 0.190 0.952 1.000 0.017
0.024
0.020
Attention and calculation 3.00 ± 2.11 3.10 ± 1.96 3.21 ± 1.84 2.80 ± 1.90 5.64 ± 0.50 5.73 ± 0.47 5.64 ± 0.92 5.91 ± 0.30
P mark 0.511 0.202 0.533 0.564 1.00 0.083
Language and summary reasoning 1.81 ± 1.69 2.26 ± 1.86 1.50 ± 1.64 1.35 ± 1.59 3.33 ± 0.81 4.09 ± 0.30 3.73 ± 1.68 3.73 ± 1.74
P mark 0.014
0.040
0.039
0.033
0.314 0.473
Orientation to time and spot 2.40 ± 1.77 2.79 ± 1.96 2.36 ± 1.91 2.35 ± 1.73 5.00 ± 1.81 5.09 ± 1.22 5.36 ± 0.81 5.36 ± 1.21
P mark 0.052 0.721 0.985 0.783 0.206 0.389

An external file that holds a picture, illustration, etc.
Object name is TRC2-6-e12030-g001.jpg

Neuropsychiatric assessments at 1‐, 3‐, and 6‐month prepare‐up in hyperbaric oxygen treated Alzheimer’s disease (AD) and control AD patients. A and B, Changes of Mini‐Psychological Divulge Examination (MMSE) and Montreal Cognitive Review (MoCA) rankings at 1‐, 3‐, and 6‐month prepare‐up in AD after hyperbaric oxygen medication versus control AD when in contrast to baseline, respectively. Recordsdata had been supplied as imply ± same outdated deviation. Recordsdata of MMSE ranking in 1‐ and 6‐month prepare‐up and MoCA ranking in 1‐, 3‐, and 6‐month prepare‐up had been analyzed by Mann‐Whitney test; records of MMSE ranking in 3 months modified into once analyzed by t test. Sample size: n = 10 in 1‐month prepare‐up, n = 9 in 3‐month prepare‐up, and n = 11 in 6‐month prepare‐up as much as the mark community; n = 42 in 1‐ and 3‐month prepare‐up, n = 40 in 6‐month prepare‐up in AD. *< 0.05

3.2. ADL in AD and aMCI patients sooner than and after hyperbaric oxygen medication

As in contrast with the baseline stage, the day to day residing actions of AD patients had been tremendously improved at 1‐month and 3‐month prepare‐up after hyperbaric oxygen medication (Desk 3). There beget been no important differences in ADL rankings of aMCI patients after the hyperbaric oxygen medication (Desk 3).

TABLE 3

Self‐comparison of ADL rankings in AD and aMCI patients sooner than and after hyperbaric oxygen medication

AD aMCI
Time Suggest ± SD P mark Suggest ± SD P mark
Baseline 38.19 ± 13.90 21.00 ± 1.26
1‐month prepare‐up 36.40 ± 13.89 0.008
21.00 ± 1.41 1.000
3‐month prepare‐up 35.07 ± 14.14 0.004
21.18 ± 1.78 0.655
6‐month prepare‐up 38.12 ± 14.21 0.678 20.73 ± 0.90 0.180

3.3. MMSE, MoCA, and ADL rankings in various levels, medicines, and sexes in AD patients after hyperbaric oxygen medication

The variation of MMSE, MoCA, and ADL rankings in disease levels, medicines, and sexes AD patients modified into once additional analyzed. As confirmed in Desk S2 in supporting files, the MMSE ranking modified into once elevated tremendously at 1‐month prepare‐up after hyperbaric oxygen medication in soft AD patients, the MoCA ranking modified into once improved tremendously at 1‐month prepare‐up after hyperbaric oxygen medication in soft and average AD patients, and the ADL ranking modified into once elevated tremendously at 1‐month prepare‐up after hyperbaric oxygen medication in average AD patients. The variation of MMSE, MoCA, and ADL rankings in AD patients with medicines is confirmed in Desk S3 in supporting files. The MMSE ranking modified into once elevated tremendously at 1‐month prepare‐up after hyperbaric oxygen medication in AD patients maintained with ChEIs. And the MoCA ranking modified into once improved tremendously at 1‐month prepare‐up after hyperbaric oxygen medication in AD patients with blended medicines (ChEIs + NMDA receptor antagonist). The ADL ranking modified into once improved tremendously at 1‐ and 3‐month prepare‐up after hyperbaric oxygen medication in AD patients with ChEIs. The variation of MMSE, MoCA, and ADL rankings in AD patients female and male is confirmed in Desk S4 in supporting files. The MMSE and MoCA rankings had been improved tremendously at 1‐month prepare‐up after hyperbaric oxygen medication in both sexes. And the ADL ranking modified into once elevated tremendously at 1‐ and 3‐month prepare‐up after hyperbaric oxygen medication in feminine AD patients.

3.4. Fluorodeoxyglucose positron emission tomography imaging sooner than and after hyperbaric oxygen medication

The representative photography of AD and aMCI patients are confirmed in Figure 2. As in contrast with the photography at the baseline, because the disease, AD patients confirmed a gash value of glucose metabolism in brain areas including heavenly medial frontal gyrus, heavenly posterior cingulate cortex, parietotemporal cortex, superior lateral temporal cortex, and left abominable frontal gyrus, but the hyperbaric oxygen medication ameliorated the diminished glucose metabolism in brain areas including left medial frontal gyrus, heavenly heart frontal gyrus, heavenly abominable parietal lobule, left anterior cingulate gyrus, heavenly associative visual cortex, left Broca dwelling, and left abominable lateral anterior temporal cortex. Furthermore, aMCI patients confirmed more brain areas with improved glucose metabolism including heart frontal gyrus, heavenly abominable parietal lobule, heavenly anterior cingulate gyrus, heavenly Broca aim, left parietotemporal cortex, superior lateral temporal cortex, left abominable frontal gyrus, heavenly abominable lateral anterior temporal cortex, anterior medial temporal cortex, and left abominable lateral posterior temporal cortex after the hyperbaric oxygen medication.

An external file that holds a picture, illustration, etc.
Object name is TRC2-6-e12030-g002.jpg

Representative photography of fluorodeoxyglucose positron emission tomography. A, photography of Alzheimer’s disease (AD) patients sooner than and 1 month after hyperbaric oxygen medication; (B) photography of amnestic soft cognitive impairment (aMCI) sooner than and 1 month after hyperbaric oxygen medication

4. DISCUSSION

Rising evidence has confirmed that non‐pharmacological interventions beget promising roles in the medication of AD.
33
Non‐pharmacological therapies, equivalent to transcranial magnetic stimulation, transcranial notify most smartly-liked stimulation, light therapy, frequent and long‐period of time exercise, acupuncture, musical interventions, aromatherapy, and vagus nerve stimulation would possibly possibly well want worthwhile effects on cognitive and non‐cognitive choices.
34
,
35
,
36
,
37
,
38
,
39
,
40
,
41
Within the showcase survey, we utilized one course of 20‐day hyperbaric oxygen medication on AD and aMCI patients, exhibiting that hyperbaric oxygen medication would possibly possibly well furthermore give a enhance to cognitive aim at 1‐month prepare‐up in AD patients. Alternatively, these enhancements had been not stumbled on 3 or 6 months after medication, indicating that one course of hyperbaric oxygen medication would possibly possibly well furthermore temporarily ameliorate cognitive impairment in AD patients, but the build modified into once not permanent. In addition, the ADL ranking modified into once improved in all 1‐, 3‐, and 6‐month prepare‐up, implying that hyperbaric oxygen medication would possibly possibly well furthermore give a enhance to the patients’ day to day residing skills with a longer reduction. As in contrast with control, one course of hyperbaric oxygen medication tremendously improved cognition in AD patients at 1‐month prepare‐up, but the advance modified into once reduced with time. In aMCI patients, the hyperbaric oxygen medication enhanced the cognitive aim with longer worthwhile build. The outcomes of MMSE, MoCA, and ADL rankings in various levels of AD patients showcase that one course of hyperbaric oxygen medication would possibly possibly well furthermore give a enhance to cognitive impairment in AD patients with early levels. As in contrast with the for the time being accredited drug donepezil that improved cognition by 0.7 in MMSE ranking as much as 24 weeks,
42
in our survey, one course of hyperbaric oxygen medication can tremendously make stronger AD patients’ choices by 1.24 for not not as much as 1 month, indicating that such medication is a promising different therapy for AD, and it is feasible that more than one courses of such therapy would possibly possibly well want tremendously longer advantages to AD patients. The footage confirmed that hyperbaric oxygen medication improved the glucose metabolism of AD patients in medial frontal gyrus connected to government aim,
43
and Broca dwelling connected to language processing,
44
which beget been per the implications of the MoCA rankings. Thus, hyperbaric oxygen medication would possibly possibly well furthermore ameliorate cognitive aim, extend the disease growth, and give a enhance to day to day residing actions in patients with AD in a restricted length. More interestingly, the MMSE rankings in aMCI patients had been tremendously improved at 3‐month prepare‐up, and the MoCA rankings had been tremendously improved at 1‐month and 6‐month prepare‐up. Pictures also confirmed improvement of glucose metabolism in brain areas connected to language aim in aMCI patients, equivalent to Broca dwelling, abominable frontal gyrus, and superior lateral temporal cortex, and in brain areas linked to reminiscence, equivalent to anterior medial temporal lobe. The improvement of glucose metabolism perceived to be better in aMCI patients than that in AD patients. The therapeutic effects in aMCI patients showcase that hyperbaric oxygen medication would possibly possibly well furthermore very smartly be a preventive design by blockading the conversion of aMCI to AD.

Hyperbaric oxygen medication is a catch and mechanically mature medical map. Accepted problems of hyperbaric oxygen medication comprise headache, claustrophobia, reversible myopia, and seizure. Most of these problems are soft and reversible when the medication is stopped.
45
Some severe problems, equivalent to oxygen toxicity and irreversible nuclear cataracts, are extraordinarily uncommon.
46
,
47
In our survey, easiest two patients skilled ear discomfort each and every now and again and the symptom modified into once relieved when the map ended. Thus, hyperbaric oxygen medication below 1.2 same outdated atmospheres and <1 hour per day is catch.

Aβ and tau pathologies are the 2 main hypotheses in AD onset and development. Our old survey reported that chronic hypoxia can build bigger Aβ deposition and put off studying and reminiscence deficits in AD mice.
5
Furthermore, we stumbled on that chronic hypoxia can make stronger the γ‐secretase exercise to promote Aβ manufacturing thru the downregulation of the DNA methyltransferase 3b to lower the methylation at CpG sites in promoter aim of genes of γ‐secretase substances, indicating that chronic hypoxia can irritate AD pathology thru epigenetic changes.
5
On the opposite hand, chronic hypoxia would possibly possibly well furthermore upregulate protein kinases, including GSK‐3β and CDK5, and suppress phosphatase, PP2A, ensuing in an enhanced tau phosphorylation.
48
,
49
Attributable to hypoxia is obsessed on AD pathogenesis, hyperbaric oxygen medication focused on hypoxia would possibly possibly well furthermore be priceless to extend or ameliorate the event of AD. Compare beget confirmed that hyperbaric oxygen medication can present a enhance to cognitive behavioral performance, lower Aβ load and tau hyperphosphorylation, and alleviate neuroinflammation in AD mouse devices.
50
Compare beget also confirmed that hyperbaric oxygen reduced lipid peroxidation, inhibited leucocyte activation, and restored the purposeful blood‐brain barrier.
16
Hyperbaric oxygen medication would possibly possibly well furthermore very smartly be a multi‐centered non‐pharmacological intervention for AD. The underlying mechanisms want additional investigation.

Hyperbaric oxygen medication modified into once each and every now and again studied in vascular dementia, exhibiting that such therapy would possibly possibly well furthermore give a enhance to the cognitive aim and make stronger the actions of day to day residing assessed by MMSE and ADL, respectively.
51
,
52
There modified into once easiest a case describe that hyperbaric oxygen medication would possibly possibly well furthermore reverse the patient’s symptomatic decline and build bigger global brain metabolism assessed by.
53

Within the showcase survey, pondering the ethic subject, accredited drug medication modified into once maintained in hyperbaric oxygen treated AD and control AD. It’s not known if the therapeutic build of hyperbaric oxygen medication is straight acting on brain choices or circuitously influencing the efficacy of the medicines undertaken by AD patients. A few‐heart stories with better numbers of members with or without medicines, more than one courses of therapies, and longer time prepare‐up, will beget to unexcited be utilized in the long flee survey. Furthermore, more measurements of AD development as smartly as to neuropsychiatric assessments, equivalent to Aβ ranges and neuroimaging, will beget to unexcited be performed. Furthermore, earlier utility of hyperbaric oxygen medication in aMCI or in the early stage AD is ceaselessly important to validate if the map can block the conversion from aMCI to AD and lower the cognitive decline in AD.

CONFLICTS OF INTEREST

The total authors beget no conflicts of passion to give an clarification for.

Supporting files

Supplementary files

ACKNOWLEDGMENTS

This work modified into once supported in share by funding from the National Natural Sciences Foundation of China (NSFC 81430021 and 81771521).

Notes


Chen J, Zhang F, Zhao L, et al. Hyperbaric oxygen ameliorates cognitive impairment in patients with Alzheimer’s disease and amnestic soft cognitive impairment. Alzheimer’s Dement. 2020;6:e12030
10.1002/trc2.12030
[CrossRef] [Google Scholar]

Jianwen Chen, Feng Zhang and Li Zhao: These authors contributed equally to this work.

REFERENCES

1.
Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1: 15056. [PubMed] [Google Scholar]

2.
Karch CM, Cruchaga C, Goate AM. Alzheimer’s disease genetics: from the bench to the medical institution. Neuron. 2014;83: 11‐26. [PMC free article] [PubMed] [Google Scholar]

3.
Reitz C, Mayeux R. Alzheimer disease: epidemiology, diagnostic criteria, threat components and biomarkers. Biochem Pharmacol. 2014;88: 640‐651. [PMC free article] [PubMed] [Google Scholar]

4.
Zhang F, Niu L, Li S, Le W. Pathological impacts of chronic hypoxia on Alzheimer’s disease. ACS Chem Neurosci. 2019;10: 902‐909. [PubMed] [Google Scholar]

5.
Liu H, Qiu H, Yang J, Ni J, Le W. Continual hypoxia facilitates Alzheimer’s disease thru demethylation of gamma‐secretase by downregulating DNA methyltransferase 3b. Alzheimers Dement. 2016;12: 130‐143. [PubMed] [Google Scholar]

6.
Liu H, Qiu H, Xiao Q, Le W. Continual hypoxia‐led to autophagy aggravates the neuropathology of Alzheimer’s disease thru AMPK‐mTOR signaling in the APPSwe/PS1dE9 mouse model. J Alzheimers Dis. 2015;48: 1019‐1032. [PubMed] [Google Scholar]

7.
Li L, Zhang X, Yang D, Luo G, Chen S, Le W. Hypoxia increases Abeta generation by altering beta‐ and gamma‐cleavage of APP. Neurobiol Increasing outdated. 2009;30: 1091‐1098. [PubMed] [Google Scholar]

8.
Zhang F, Zhong R, Qi H, et al. Impacts of acute hypoxia on Alzheimer’s disease‐like pathologies in APP(swe)/PS1(dE9) mice and their wild kind littermates. Front Neurosci. 2018;12: 314. [PMC free article] [PubMed] [Google Scholar]

9.
Daulatzai MA. Death by a thousand cuts in Alzheimer’s disease: hypoxia–the prodrome. Neurotox Res. 2013;24: 216‐243. [PubMed] [Google Scholar]

10.
Lin PJ, Zhong Y, Fillit HM, Cohen JT, Neumann PJ. Hospitalizations for ambulatory care soft cases and unplanned readmissions amongst medicare beneficiaries with Alzheimer’s disease. Alzheimers Dement. 2017;13: 1174‐1178. [PubMed] [Google Scholar]

11.
Yaffe K, Laffan AM, Harrison SL, et al. Sleep‐disordered respiration, hypoxia, and threat of soft cognitive impairment and dementia in older girls. JAMA. 2011;306: 613‐619. [PMC free article] [PubMed] [Google Scholar]

12.
Sharma VK, Das SK, Dhar P, et al. Domain converse changes in cognition at excessive altitude and its correlation with hyperhomocysteinemia. PLoS One. 2014;9:e101448. [PMC free article] [PubMed] [Google Scholar]

13.
Rimoldi SF, Rexhaj E, Duplain H, et al. Acute and chronic altitude‐led to cognitive dysfunction in younger folks and formative years. J Pediatr. 2016;169: 238‐243. [PubMed] [Google Scholar]

14.
Hu SL, Xiong W, Dai ZQ, Zhao HL, Feng H. Cognitive changes for the length of prolonged protect at excessive altitude and its correlation with C‐reactive protein. PLoS One. 2016;11:e0146290. [PMC free article] [PubMed] [Google Scholar]

15.
Huang CC, Ho CH, Chen YC, et al. Hyperbaric oxygen therapy is expounded to lower short‐ and long‐period of time mortality in patients with carbon monoxide poisoning. Chest. 2017;152: 943‐953. [PubMed] [Google Scholar]

16.
Bennett MH, Weibel S, Wasiak J, Schnabel A, French C, Kranke P. Hyperbaric oxygen therapy for acute ischaemic stroke. Cochrane Database Syst Rev. 2014(11):CD004954. [PubMed] [Google Scholar]

17.
Ferri CP, Prince M, Brayne C, et al. World prevalence of dementia: a Delphi consensus survey. Lancet. 2005;366: 2112‐2117. [PMC free article] [PubMed] [Google Scholar]

18.
Chu LW. Alzheimer’s disease: early diagnosis and medication. Hong Kong Med J.. 2012;18: 228‐237. [PubMed] [Google Scholar]

19.
Graham WV, Bonito‐Oliva A, Sakmar TP. Update on Alzheimer’s disease therapy and prevention suggestions. Annu Rev Med. 2017;68: 413‐430. [PubMed] [Google Scholar]

20.
Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F. New pharmacological suggestions for medication of Alzheimer’s disease: kind out disease editing remedy. Br J Clin Pharmacol. 2012;73: 504‐517. [PMC free article] [PubMed] [Google Scholar]

21.
Pedersen JT, Sigurdsson EM. Tau immunotherapy for Alzheimer’s disease. Traits Mol Med. 2015;21: 394‐402. [PubMed] [Google Scholar]

22.
Khachaturian ZS, Kuller LH, Khachaturian AS. Strategic objectives and roadmap for dementia prevention by stroke prevention. Alzheimers Dement. 2019;15: 865‐869. [PubMed] [Google Scholar]

23.
Hachinski V, Einhaupl K, Ganten D, et al. Battling dementia by combating stroke: the Berlin Manifesto. Alzheimers Dement. 2019;15: 961‐984. [PMC free article] [PubMed] [Google Scholar]

24.
Sachdev PS, Blacker D, Blazer DG, et al. Classifying neurocognitive problems: the DSM‐5 means. Nat Rev Neurol. 2014;10: 634‐642. [PubMed] [Google Scholar]

25.
Dubois B, Feldman HH, Jacova C, et al. Compare criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS‐ADRDA criteria. Lancet Neurol. 2007;6: 734‐746. [PubMed] [Google Scholar]

26.
Frota NAF, Nitrini R, Damasceno BP, et al. Standards for the diagnosis of Alzheimer’s disease: suggestions of the Scientific Division of Cognitive Neurology and Increasing outdated of the Brazilian Academy of Neurology. Dement Neuropsychol. 2011;5: 146‐152. [PMC free article] [PubMed] [Google Scholar]

27.
Portet F, Ousset PJ, Visser PJ, et al. Indifferent cognitive impairment (MCI) in medical prepare: an vital review of the notion that and fresh diagnostic map. Document of the MCI Working Neighborhood of the European Consortium on Alzheimer’s Illness. J Neurol Neurosurg Psychiatry. 2006;77: 714‐718. [PMC free article] [PubMed] [Google Scholar]

28.
Petersen RC. Indifferent cognitive impairment as a diagnostic entity. J Intern Med. 2004;256: 183‐194. [PubMed] [Google Scholar]

29.
Folstein MF, Folstein SE, McHugh PR. “Mini‐psychological command”. A purposeful blueprint for grading the cognitive command of patients for the clinician. J Psychiatr Res. 1975;12: 189‐198. [PubMed] [Google Scholar]

30.
Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Review, MoCA: a transient screening tool for soft cognitive impairment. J Am Geriatr Soc. 2005;53: 695‐699. [PubMed] [Google Scholar]

31.
Velayudhan L, Ryu SH, Raczek M, et al. Overview of transient cognitive tests for patients with suspected dementia. Int Psychogeriatr. 2014;26: 1247‐1262. [PMC free article] [PubMed] [Google Scholar]

32.
Sikkes SA, de Lange‐de Klerk ES, Pijnenburg YA, Scheltens P, Uitdehaag BM. A systematic review of instrumental actions of day to day residing scales in dementia: room for improvement. J Neurol Neurosurg Psychiatry. 2009;80:7‐12. [PubMed] [Google Scholar]

33.
Bahar‐Fuchs A, Clare L, Woods B. Cognitive coaching and cognitive rehabilitation for folks with soft to average dementia of the Alzheimer’s or vascular kind: a review. Alzheimers Res Ther. 2013;5: 35. [PMC free article] [PubMed] [Google Scholar]

34.
Revesz D, Rydenhag B, Ben‐Menachem E. Complications and security of vagus nerve stimulation: 25 years of ride at a single heart. J Neurosurg Pediatr. 2016;18: 97‐104. [PubMed] [Google Scholar]

35.
Wang Z, Liang P, Zhao Z, et al. Acupuncture modulates resting command hippocampal purposeful connectivity in Alzheimer disease. PLoS One. 2014;9:e91160. [PMC free article] [PubMed] [Google Scholar]

36.
Jimbo D, Kimura Y, Taniguchi M, Inoue M, Urakami K. Affect of aromatherapy on patients with Alzheimer’s disease. Psychogeriatrics. 2009;9: 173‐179. [PubMed] [Google Scholar]

37.
Ohman H, Savikko N, Strandberg TE, et al. Outcomes of exercise on cognition: the finnish Alzheimer disease exercise trial: a randomized, controlled trial. J Am Geriatr Soc. 2016;64: 731‐738. [PubMed] [Google Scholar]

38.
Samson S, Clement S, Narme P, Schiaratura L, Ehrle N. Efficacy of musical interventions in dementia: methodological necessities of nonpharmacological trials. Ann N Y Acad Sci. 2015;1337: 249‐255. [PubMed] [Google Scholar]

39.
Cantone M, Di Pino G, Capone F, et al. The contribution of transcranial magnetic stimulation in the diagnosis and in the administration of dementia. Clin Neurophysiol. 2014;125: 1509‐1532. [PubMed] [Google Scholar]

40.
Riemersma‐van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, Van Someren EJ. Affect of sparkling light and melatonin on cognitive and noncognitive aim in elderly residents of community care facilities: a randomized controlled trial. JAMA. 2008;299: 2642‐2655. [PubMed] [Google Scholar]

41.
Manenti R, Cotelli M, Robertson IH, Miniussi C. Transcranial brain stimulation stories of episodic reminiscence in younger adults, elderly adults and folks with reminiscence dysfunction: a review. Mind Stimul. 2012;5: 103‐109. [PubMed] [Google Scholar]

42.
Tariot PN, Cummings JL, Katz IR, et al. A randomized, double‐blind, placebo‐controlled survey of the efficacy and security of donepezil in patients with Alzheimer’s disease in the nursing dwelling environment. J Am Geriatr Soc. 2001;49: 1590‐1599. [PubMed] [Google Scholar]

43.
Talati A, Hirsch J. Functional specialization at some point of the medial frontal gyrus for perceptual trudge/no‐trudge choices per “what,” “when,” and “the put” connected files: an fMRI survey. J Cogn Neurosci. 2005;17: 981‐993. [PubMed] [Google Scholar]

44.
Flinker A, Korzeniewska A, Shestyuk AY, et al. Redefining the aim of Broca’s dwelling in speech. Proc Natl Acad Sci U S A. 2015;112: 2871‐2875. [PMC free article] [PubMed] [Google Scholar]

45.
Dauwe PB, Pulikkottil BJ, Lavery L, Stuzin JM, Rohrich RJ. Does hyperbaric oxygen therapy work in facilitating acute harm healing: a systematic review. Plast Reconstr Surg. 2014;133: 208e‐215e. [PubMed] [Google Scholar]

46.
McMonnies CW. Hyperbaric oxygen therapy and the doable of ocular problems or contraindications. Clin Exp Optom. 2015;98: 122‐125. [PubMed] [Google Scholar]

47.
Palmquist BM, Philipson B, Barr PO. Nuclear cataract and myopia for the length of hyperbaric oxygen therapy. Br J Ophthalmol. 1984;68: 113‐117. [PMC free article] [PubMed] [Google Scholar]

48.
Gao L, Tian S, Gao H, Xu Y. Hypoxia increases Abeta‐led to tau phosphorylation by calpain and promotes behavioral penalties in AD transgenic mice. J Mol Neurosci. 2013;51: 138‐147. [PubMed] [Google Scholar]

49.
Zhang F, Chen J, Zhao L, Dong C. Candidate biomarkers of more than one plan atrophy in cerebrospinal fluid. Rev Neurosci. 2014;25: 653‐662. [PubMed] [Google Scholar]

50.
Shapira R, Solomon B, Efrati S, Frenkel D, Ashery U. Hyperbaric oxygen therapy ameliorates pathophysiology of 3xTg‐AD mouse model by attenuating neuroinflammation. Neurobiol Increasing outdated. 2018;62: 105‐119. [PubMed] [Google Scholar]

51.
Xu Y, Wang Q, Qu Z, Yang J, Zhang X, Zhao Y. Preserving build of hyperbaric oxygen therapy on cognitive aim in patients with vascular dementia. Cell Transplant. 2019;28: 1071‐1075. [PMC free article] [PubMed] [Google Scholar]

52.
Xiao Y, Wang J, Jiang S, Luo H. Hyperbaric oxygen therapy for vascular dementia. Cochrane Database Syst Rev. 2012(7):CD009425. [PubMed] [Google Scholar]

53.
Harch PG, Fogarty EF. Hyperbaric oxygen therapy for Alzheimer’s dementia with positron emission tomography imaging: a case describe. Med Fuel Res. 2018;8: 181‐184. [PMC free article] [PubMed] [Google Scholar]

Be taught More

Leave a Reply

Your email address will not be published. Required fields are marked *