Aniracetam

Findings:

TARP γ-8 KO adolescent mice exhibited hyperactivity, anxiety-like behaviors, impulsivity, reduced recognition memory, and impaired short-term and long-term contextual fear memory compared to WT mice. Administration of aniracetam (100 mg/kg, i.p.) significantly ameliorated these behavioral deficits in the TARP γ-8 KO mice. The study suggests aniracetam works through glutamate receptors (AMPARs) and shows potential as a novel treatment for ADHD symptoms.

Participants:

Animal model: TARP γ-8 knockout (KO) mice and wild-type (WT) littermates (C57BL/6J background). Four-to eight-week-old male mice (weight, 13.2–20.5 g) were used. n = 10 mice per group.

Dosage:

100 mg/kg aniracetam administered via intraperitoneal (i.p.) injection 30 minutes before behavioral testing.

Study Quality Assessment:

Animal model study using TARP γ-8 KO mice as an ADHD model compared to WT controls. Vehicle control used (10% 2-hydroxypropyl-β-cyclodextrin). Behavioral tests conducted: Open field, Cliff avoidance, Novel object recognition, Contextual fear conditioning. Statistical methods specified (ANOVA, Kruskal-Wallis, post-hoc tests). Sample size reported as n=10 per group. Study approved by Ethics Committee (IACUC-hebmu-2019001) and followed ARRIVE guidelines. Reviewer comments noted limitations (model generalizability, lack of direct attention measure, sample size rationale not detailed). Authors declared no competing financial interests.

All Effects:

Findings:

Aniracetam is described as a safe, effective, cognitive-enhancing drug that improves memory in human and animal studies. This paper proposes an evidence-based model suggesting aniracetam may prevent amyloid-β (Aβ) plaque accumulation by increasing α-secretase activity through two pathways: enhancing Brain-Derived Neurotrophic Factor (BDNF) expression and positively modulating metabotropic glutamate receptors (mGluRs). The text notes this is the first paper to propose this specific model and that direct research on aniracetam's effect on Aβ is lacking.

Participants:

The text describes aniracetam as improving memory in 'human and animal studies'. It cites specific clinical trials involving '109 elderly subjects' and '115 subjects'. Future research is proposed involving 'adults with mild cognitive impairment' and 'rats'. The primary text itself is a review/model proposal, not a report on a single study with its own participant group.

Dosage:

A future human clinical trial is proposed using '1,500 mg/day of aniracetam'. A future animal study is proposed using a 'daily dose of aniracetam (50 mg/kg) in rats'.

Study Quality Assessment:

The text presents an 'evidence-based model' citing numerous references. It mentions cited clinical trials were 'placebo controlled' [refs 61, 62] with durations of 'six months' [refs 61, 62] and sample sizes N=109 [ref 61] and N=115 [ref 62]. Limitations are acknowledged, including unknowns in AD neurobiochemistry, Aβ biology, long-term effects of α-secretase upregulation, and incomplete understanding of aniracetam's biochemistry (e.g., specific mGluRs modulated, specific α-secretases activated). Funding sources are disclosed ('Brain Fit For Life, LLC', 'private donors'). A conflict of interest statement is included ('author has no conflict of interest'). Data availability is stated ('All data are available in the main text'). The article is published in a peer-reviewed journal (J Alzheimers Dis) and is open access (CC BY-NC 4.0).

All Effects:

Findings:

Aniracetam monotherapy preserved cognitive, functional, and psychological parameters over 12 months and improved emotional state (GDS) at 3 months. In patients with mild-to-moderate dementia (MMSE 15-25), aniracetam showed significantly better cognitive performance (MMSE) at 6 months and improved functionality (FRSSD) at 3 months compared to ChEIs. Patients on ChEIs monotherapy showed significant cognitive decline (MMSE) at 12 months. Aniracetam was well-tolerated.

Participants:

N=276 patients (mean age 71 ± 8 years, 95 males) diagnosed with cognitive disorders of variable severity (including Mild Cognitive Impairment, Alzheimer's disease, and other dementias like vascular, mixed, frontotemporal). Inclusion criteria included age ≥ 50 years, diagnosis of cognitive impairment (DSM-IV), reliable caregiver, and recent neuroimaging. Exclusion criteria included severe comorbidities or other neuropsychiatric disorders. A sub-analysis focused on N=151 patients with mild-to-moderate dementia (baseline MMSE 15-25).

Dosage:

Aniracetam: 1500 mg daily fixed dose. ChEIs: Variable optimal dosages depending on the specific agent, reached after appropriate escalation. Combined treatment involved both aniracetam (1500 mg/day) and a ChEI.

Study Quality Assessment:

Prospective, open-label, comparative study. Sample size N=276, divided into four groups (no treatment, aniracetam mono, ChEIs mono, combined). Neuropsychological assessment using validated scales (MMSE, FRSSD, GDS, NPI) performed by a blinded rater at baseline, 3, 6, and 12 months. Attempted rough randomization for treatment allocation, but not computer-generated. Limitations acknowledged: open-label design, not placebo-controlled (no-treatment group served as control), relatively small number of patients per group, potential limitations of neuropsychological tools used, exclusion of 7 patients who switched treatment. Conflict of Interest: Authors declared no financial conflicts.

All Effects:

Findings:

Aniracetam monotherapy (1500mg/day) maintained cognitive, functional, and neuropsychiatric parameters over 12 months and significantly improved emotional state (GDS) at 3 months in the overall group. In patients with mild-moderate dementia (MMSE 15-25), aniracetam showed significantly better cognitive performance (MMSE) at 6 months and improved functionality (FRSSD) at 3 months compared to ChEIs alone. ChEIs monotherapy showed significant cognitive decline (MMSE) at 12 months, even in the mild-moderate subgroup.

Participants:

N=276 patients (mean age 71 ± 8 years, 95 males) with cognitive disorders (including Mild Cognitive Impairment, Alzheimer's disease, and other forms of dementia like vascular, mixed, and frontotemporal). A sub-analysis focused on N=151 patients with mild-to-moderate dementia (baseline MMSE 15-25).

Dosage:

Aniracetam: 1500 mg daily fixed dose. ChEIs: Dosages were variable depending on the specific agent, adjusted based on prescribing information, clinical judgment, tolerance, and response, aiming for optimal dosages after escalation.

Study Quality Assessment:

Prospective, open-label, comparative study. N=276 allocated into four groups (no treatment n=75, aniracetam n=58, ChEIs n=68, combined n=68). Assessments via validated scales (MMSE, FRSSD, GDS, NPI) at baseline, 3, 6, 12 months. Rater blinded to treatment. Allocation described as 'roughly randomized manner' by clinicians, not computer-generated. Limitations acknowledged: open-label, not placebo-controlled, potential bias in no-treatment group selection, 7 subjects excluded post-allocation due to treatment switching, use of MMSE noted as potentially 'moderately sensitive and rather crude', relatively small number of patients per group.

All Effects:

Participants:

youths with attention deficit hyperactivity disorder

Study Quality Assessment:

systematic review and meta-analysis of clinical trials and biological studies