Cognitive Impairment after Small-dose Ketamine Isomers in Comparison to Equianalgesic Racemic Ketamine in Human Volunteers

Background Ketamine is increasingly used in pain therapy but may impair brain functions. Mood and cognitive capacities were compared after equianalgesic small-dose S(+)-, R(-)-, and racemic ketamine in healthy volunteers. Methods Twenty-four subjects received intravenous 0.5 mg/kg racemic, 0.25 mg/kg S(+)-, and 1.0 mg/kg R(-)-ketamine in a prospective, randomized, double-blind, crossover study. Hemodynamic variables, mood, and cognitive capacities were assessed for 60 min. Results Transient increases in blood pressure, heart rate, and catecholamines were similar after administration of all drugs. At 20 min after injection, subjects felt less decline in concentration and were more brave after S(+)- than racemic ketamine. They reported being less lethargic but more out-of-control after R(-)- than racemic ketamine. Ketamine isomers induced less drowsiness, less lethargy, and less impairment in clustered subjective cognitive capacity than racemic ketamine for the 60-min study. Objective concentration capacity [test time, S(+): 25.4 +/- 15.2 s, R(-): 34.8 +/- 18.4 s, racemic ketamine: 40.8 +/- 20.8 s, mean +/- SD] and retention in primary memory [test time, S(+): 4.6 +/- 1.2 s, R(-): 4.2 +/- 1.4 s, racemic ketamine: 4.0 +/- 1.4 s, mean +/- SD] declined less after S(+)- than either R(-)- or racemic ketamine at 1 min. At 5 min, immediate recall, anterograde amnesia, retention in primary memory, short-term storage capacity, and intelligence quotient were less reduced after the isomers than racemic ketamine. Speed reading and central information flow decreased less after S(+)- than racemic ketamine. Conclusions Early after injection, ketamine isomers induce less tiredness and cognitive impairment than equianalgesic small-dose racemic ketamine. In addition, S(+)-ketamine causes less decline in concentration capacity and primary memory. The differences in drug effects cannot be explained by stereoselective action on one given receptor.

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A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment

Journal of Chinese Integrative Medicine ◽

10.3736/jcim20080106 ◽

2008 ◽

Vol 6 (1) ◽

pp. 25-31 ◽

Cited By ~ 11

Author(s):

Hao Li

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Double Blind Trial ◽

Double Blind ◽

Blind Trial ◽

Randomized Controlled

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CHF5074 Reduces Biomarkers of Neuroinflammation in Patients with Mild Cognitive Impairment: A 12-Week, Double-Blind, Placebo- Controlled Study

Current Alzheimer Research ◽

10.2174/13892037113149990144 ◽

2013 ◽

Vol 10 (7) ◽

pp. 742-753 ◽

Cited By ~ 50

Author(s):

Joel Ross ◽

Sanjiv Sharma ◽

Jaron Winston ◽

Margarita Nunez ◽

Gabriella Bottini ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo

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Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment

Journal of Alzheimer s Disease ◽

10.3233/jad-210137 ◽

2021 ◽

pp. 1-19

Author(s):

Joanna Perła-Kaján ◽

Olga Włoczkowska ◽

Anetta Zioła-Frankowska ◽

Marcin Frankowski ◽

A. David Smith ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Controlled Trial ◽

Verbal Learning ◽

Cognitive Status ◽

B Vitamins ◽

Paraoxonase 1 ◽

Phenyl Acetate ◽

Double Blind ◽

Trail Making

Background: Identification of modifiable risk factors that affect cognitive decline is important for the development of preventive and treatment strategies. Status of paraoxonase 1 (PON1), a high-density lipoprotein-associated enzyme, may play a role in the development of neurological diseases, including Alzheimer’s disease. Objective: We tested a hypothesis that PON1 status predicts cognition in individuals with mild cognitive impairment (MCI). Methods: Individuals with MCI (n = 196, 76.8-years-old, 60% women) participating in a randomized, double-blind placebo-controlled trial (VITACOG) were assigned to receive a daily dose of folic acid (0.8 mg), vitamin B12 (0.5 mg) and B6 (20 mg) (n = 95) or placebo (n = 101) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of participants (n = 168) by MRI. PON1 status, including PON1 Q192R genotype, was determined by quantifying enzymatic activity of PON1 using paraoxon and phenyl acetate as substrates. Results: In the placebo group, baseline phenylacetate hydrolase (PhAcase) activity of PON1 (but not paraoxonase activity or PON1 Q192R genotype) was significantly associated with global cognition (Mini-Mental State Examination, MMSE; Telephone Inventory for Cognitive Status-modified, TICS-m), verbal episodic memory (Hopkins Verbal Learning Test-revised: Total Recall, HVLT-TR; Delayed Recall, HVLT-DR), and attention/processing speed (Trail Making A and Symbol Digits Modalities Test, SDMT) at the end of study. In addition to PhAcase, baseline iron and triglycerides predicted MMSE, baseline fatty acids predicted SDMT, baseline anti-N-Hcy-protein autoantibodies predicted TICS-m, SDMT, Trail Making A, while BDNF V66M genotype predicted HVLT-TR and HVLT-DR scores at the end of study. B-vitamins abrogated associations of PON1 and other variables with cognition. Conclusion: PON1 is a new factor associated with impaired cognition that can be ameliorated by B-vitamins in individuals with MCI.

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Effects of 12 Weeks Cosmos caudatus Supplement among Older Adults with Mild Cognitive Impairment: A Randomized, Double-Blind and Placebo-Controlled Trial

Nutrients ◽

10.3390/nu13020434 ◽

2021 ◽

Vol 13 (2) ◽

pp. 434

Author(s):

Yee Xing You ◽

Suzana Shahar ◽

Nor Fadilah Rajab ◽

Hasnah Haron ◽

Hanis Mastura Yahya ◽

...

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Controlled Trial ◽

Mood Disturbance ◽

Double Blind ◽

Blood Biochemical ◽

Cosmos Caudatus ◽

Total Mood Disturbance ◽

Biochemical Profiles

Cosmos caudatus (CC) contains high flavonoids and might be beneficial in neuroprotection. It has the potential to prevent neurodegenerative diseases. Therefore, we aimed to investigate the effects of 12 weeks of Cosmos caudatus supplement on cognitive function, mood status, blood biochemical profiles and biomarkers among older adults with mild cognitive impairment (MCI) through a double-blind, placebo-controlled trial. The subjects were randomized into CC supplement (n = 24) and placebo group (n = 24). Each of them consumed one capsule of CC supplement (250 mg of CC/capsule) or placebo (500 mg maltodextrin/capsule) twice daily for 12 weeks. Cognitive function and mood status were assessed at baseline, 6th week, and 12th week using validated neuropsychological tests. Blood biochemical profiles and biomarkers were measured at baseline and 12th week. Two-way mixed analysis of variance (ANOVA) analysis showed significant improvements in mini mental state examination (MMSE) (partial η2 = 0.150, p = 0.049), tension (partial η2 = 0.191, p = 0.018), total mood disturbance (partial η2 = 0.171, p = 0.028) and malondialdehyde (MDA) (partial η2 = 0.097, p = 0.047) following CC supplementation. In conclusion, 12 weeks CC supplementation potentially improved global cognition, tension, total mood disturbance, and oxidative stress among older adults with MCI. Larger sample size and longer period of intervention with incorporation of metabolomic approach should be conducted to further investigate the underlying mechanism of CC supplementation in neuroprotection.

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Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial

Journal of Alzheimer s Disease ◽

10.3233/jad-200997 ◽

2021 ◽

pp. 1-13

Author(s):

Dong Bai ◽

Junting Fan ◽

Mengyue Li ◽

Cuixia Dong ◽

Yiming Gao ◽

...

Keyword(s):

Cognitive Impairment ◽

Folic Acid ◽

Mild Cognitive Impairment ◽

Cognitive Function ◽

Digit Span ◽

Controlled Trial ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Double Blind ◽

Full Scale Intelligence Quotient

Background: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. Objective: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. Methods: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged > 60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. Results: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (–6.51, –10.57 to –2.45) compared to placebo. DHA lower the Aβ40 levels (–40.57, –79.79 to –1.35) compared to placebo (p < 0.05), and folic acid + DHA reduced the Aβ42 (–95.59, –150.76 to –40.43) and Aβ40 levels (–45.75, –84.67 to –6.84) more than DHA (p < 0.05). Conclusion: Folic acid and DHA improve cognitive function and reduce blood Aβ production in MCI patients. Combination therapy may be more beneficial in reducing blood Aβ-related biomarkers.

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Adjunctive treatment for cognitive impairment in patients with chronic schizophrenia: a double-blind, placebo-controlled study

Neuropsychiatric Disease and Treatment ◽

10.2147/ndt.s64189 ◽

2014 ◽

pp. 1317 ◽

Cited By ~ 1

Author(s):

Xiaofeng Guo ◽

Weiwei Zhu ◽

Zhanchou Zhang ◽

Jingfeng Qi ◽

Fang Liu ◽

...

Keyword(s):

Cognitive Impairment ◽

Chronic Schizophrenia ◽

Adjunctive Treatment ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo

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Random Forest Model in the Diagnosis of Dementia Patients with Normal Mini-Mental State Examination Scores

Journal of Personalized Medicine ◽

10.3390/jpm12010037 ◽

2022 ◽

Vol 12 (1) ◽

pp. 37

Author(s):

Jie Wang ◽

Zhuo Wang ◽

Ning Liu ◽

Caiyan Liu ◽

Chenhui Mao ◽

...

Keyword(s):

Machine Learning ◽

Cognitive Impairment ◽

Random Forest ◽

Mental State ◽

Mini Mental State Examination ◽

Machine Learning Algorithms ◽

Assessment Model ◽

Test Time ◽

Cognitive Screening ◽

State Examination

Background: Mini-Mental State Examination (MMSE) is the most widely used tool in cognitive screening. Some individuals with normal MMSE scores have extensive cognitive impairment. Systematic neuropsychological assessment should be performed in these patients. This study aimed to optimize the systematic neuropsychological test battery (NTB) by machine learning and develop new classification models for distinguishing mild cognitive impairment (MCI) and dementia among individuals with MMSE ≥ 26. Methods: 375 participants with MMSE ≥ 26 were assigned a diagnosis of cognitively unimpaired (CU) (n = 67), MCI (n = 174), or dementia (n = 134). We compared the performance of five machine learning algorithms, including logistic regression, decision tree, SVM, XGBoost, and random forest (RF), in identifying MCI and dementia. Results: RF performed best in identifying MCI and dementia. Six neuropsychological subtests with high-importance features were selected to form a simplified NTB, and the test time was cut in half. The AUC of the RF model was 0.89 for distinguishing MCI from CU, and 0.84 for distinguishing dementia from nondementia. Conclusions: This simplified cognitive assessment model can be useful for the diagnosis of MCI and dementia in patients with normal MMSE. It not only optimizes the content of cognitive evaluation, but also improves diagnosis and reduces missed diagnosis.

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Digital Screening for Cognitive Impairment – A Proof of Concept Study

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2021.2 ◽

2021 ◽

pp. 1-8

Author(s):

V. Bloniecki ◽

G. Hagman ◽

M. Ryden ◽

M. Kivipelto

Keyword(s):

Cognitive Impairment ◽

Neurodegenerative Disorder ◽

Early Stage ◽

Roc Curves ◽

University Hospital ◽

Cognitive Test ◽

Test Time ◽

Proof Of Concept ◽

Cognitive Screening ◽

Disease Modifying Drugs

Background: Due to an ageing demographic and rapid increase of cognitive impairment and dementia, combined with potential disease-modifying drugs and other interventions in the pipeline, there is a need for the development of accurate, accessible and efficient cognitive screening instruments, focused on early-stage detection of neurodegenerative disorders. Objective: In this proof of concept report, we examine the validity of a newly developed digital cognitive test, the Geras Solutions Cognitive Test (GCST) and compare its accuracy against the Montreal Cognitive Assessment (MoCA). Methods: 106 patients, referred to the memory clinic, Karolinska University Hospital, due to memory complaints were included. All patients were assessed for presence of neurodegenerative disorder in accordance with standard investigative procedures. 66% were diagnosed with subjective cognitive impairment (SCI), 25% with mild cognitive impairment (MCI) and 9% fulfilled criteria for dementia. All patients were administered both MoCA and GSCT. Descriptive statistics and specificity, sensitivity and ROC curves were established for both test. Results: Mean score differed significantly between all diagnostic subgroups for both GSCT and MoCA (p<0.05). GSCT total test time differed significantly between all diagnostic subgroups (p<0.05). Overall, MoCA showed a sensitivity of 0.88 and specificity of 0.54 at a cut-off of <=26 while GSCT displayed 0.91 and 0.55 in sensitivity and specificity respectively at a cut-off of <=45. Conclusion: This report suggests that GSCT is a viable cognitive screening instrument for both MCI and dementia.

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