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Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
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Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
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CNS stimulants, such as cocaine, amphetamines, and cannabinoids, have varying structures and mechanisms of action that lead to different therapeutic effects and side effects. Cocaine, with its molecular formula C17H21NO4, is a tropane alkaloid and a tertiary amino compound. It has two chemical forms: the hydrochloride salt and the "freebase." The former is in powder form, while the latter involves removing the hydrochloride salt to create a form that can be smoked. Cocaine exerts its...
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Association between CNS-active drugs and risk of Alzheimer's and age-related neurodegenerative diseases.

Helena Cortes-Flores1,2, Georgina Torrandell-Haro1,2, Roberta Diaz Brinton1,2,3

  • 1Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States.

Frontiers in Psychiatry
|March 15, 2024
PubMed
Summary

Central nervous system (CNS)-active drugs may reduce the risk of Alzheimer's Disease (AD) and other neurodegenerative diseases (NDDs). However, atypical antipsychotics increased AD risk, while combination therapy may offer protection.

Keywords:
Alzheimer’s diseaseCNS-active drugsneurodegenerative diseasesresponder analysisretrospective analysis

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Geriatrics

Background:

  • Neuropsychiatric conditions are linked to an increased risk of age-related neurodegenerative diseases (NDDs).
  • Understanding the impact of central nervous system (CNS)-active drugs on NDD risk is crucial for patient management.

Purpose of the Study:

  • To investigate the association between CNS-active drug use and the risk of developing Alzheimer's Disease (AD), non-AD dementia, Multiple Sclerosis (MS), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS).
  • To explore how different drug classes, treatment durations, and patient demographics influence this association.

Main Methods:

  • Retrospective cohort analysis of a 10-year medical claims dataset.
  • Inclusion of patients aged 60 years or older.
  • Propensity score matching for comorbidity and demographic parameters.
  • Determination of relative risk (RR) ratios, 95% confidence intervals (CI), and cumulative hazard ratios.

Main Results:

  • CNS-active drug exposure was linked to a reduced risk of AD (RR: 0.50) and all NDDs (RR: 0.54).
  • Antidepressants, sedatives, anticonvulsants, and stimulants decreased AD risk, while atypical antipsychotics increased it.
  • Risk reduction was most significant in patients aged 70+ with long-term therapy (>3 years).
  • Combination therapy, particularly Z-drug and SNRI, showed the greatest AD risk reduction.

Conclusions:

  • CNS-active drugs, excluding atypical antipsychotics, are associated with a lower risk of AD and NDDs.
  • Atypical antipsychotics may increase AD risk, but combination therapy could potentially mitigate this.
  • Findings support precision prevention strategies for NDDs in individuals with neuropsychiatric disorders.