Anti-Hypertensives Reduce the Rate of Alzheimer's Disease Progression: A Cohort Study Linked with Genetic and
Z Sternberg1, R Podolsky, J Yu
1Zohara Sternberg, PhD, Clinical Associate Professor of Neurology, Buffalo Medical Center, Buffalo, NY, 14203, Tel: 716-8597540, Fax: 716-8592430, 859-7573,
Insights
Antihypertensive medications (A.H.T.s) slow dementia progression and reduce Alzheimer's disease (A.D.) severity. Specific combinations, like diuretics with alpha-1 blockers or ACE inhibitors, offer optimal benefits for cognitive health.
Area of Science:
- Neurology
- Gerontology
- Pharmacology
Background:
- Arterial hypertension is a known risk factor for dementia development and progression, impacting both Alzheimer's disease (A.D.) and vascular pathology.
- The specific impact of different antihypertensive medication (A.H.T.) classes on dementia progression and neuropathology remains largely uncharacterized.
Purpose of the Study:
- To evaluate how various A.H.T. classes, individually and in combination, affect the rate of dementia progression.
- To analyze the influence of A.H.T.s on neuropathological markers in A.D. patients, including Braak staging, hippocampal atrophy, and cerebrospinal fluid (CSF) biomarkers.
Main Methods:
- Utilized the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) for comprehensive data analysis.
- Longitudinal study design tracking dementia progression over a 10-year period.
- Analysis included demographic stratification (age, gender, APOE4) and neuropathological assessments.
Main Results:
- A.H.T. use was associated with a significant reduction in the yearly increase of cognitive decline (CDR-SOB scores) and improved overall survival rates.
- Specific A.H.T. classes, including beta-blockers (βB) and angiotensin receptor blockers (A.R.B.s), demonstrated a slowing effect on cognitive decline.
- Combination therapies, particularly diuretics with alpha-1 blockers (α1-AB) or ACE inhibitors (ACEI), showed synergistic benefits in mitigating cognitive decline.
- Postmortem analysis revealed a lower prevalence of severe Braak staging in A.H.T. users compared to non-users.
- Significant relationships were found between hippocampal atrophy, Braak staging, and CSF P-tau levels.
Conclusions:
- Findings suggest A.H.T.s can potentially halt dementia progression, irrespective of underlying pathology (A.D. or vascular).
- Strategic selection of A.H.T. combination therapy is crucial for maximizing benefits in slowing dementia progression.
- Results indicate a more intricate model of A.D. pathogenesis, opening avenues for novel therapeutic strategies.
Background:
Arterial hypertension contributes to both the development and progression of dementia due to both Alzheimer's disease (A.D.) and vascular pathology. However, the effects of different classes of anti-hypertensives (A.H.T.s), on the rate of dementia progression and brain neuropathology are unknown.
Objective:
To investigate the effect of each class of A.H.T., both as single and combined, on the rate of dementia progression. In addition, we analyzed the effect of A.H.T.s on brain neuropathology in AD participants, indicated by Braak staging, hippocampal atrophy, and baseline CSF levels of A-β42, total (T) tau, and P-181 tau.
Methods:
We have used the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS).
Results:
A.H.T.s were associated with reduced yearly increase in the CDR-SOB scores of 1.025 during a 10-year follow-up (P<0.001). The overall survival rate was higher in A.H.T. users than non-users [HR: 0.912: 0.860, 0.967) P=0.002]. These trends continued when stratifying participants by age, gender, and APOE4 allele. Participants who did not use A.H.T.s had a mean yearly increase of 1.71±1.7 in the CDR-SOB scores. This value was reduced to 1.48±1.6, P=0.006 and 1.45±1.6, P=0.024 for participants with documented use of βB and A.R.B.s, respectively. Combining diuretics with α1-AB or ACEI led to synergistic effects in reducing the rise in CDR-SOB scores. The proportion of participants who were diagnosed having AD postmortem with severe Braak staging was significantly lower in A.H.T.-users than non-users. The severity of Braak staging, and hippocampal atrophy differed in participants> 70 vs. <70 years old, in both males and females. A significant relationship was observed between hippocampal atrophy and Braak staging; and between hippocampal atrophy and baseline CSF levels of P-181 tau.
Conclusion:
Our results could have implications for halting the progression of dementia regardless of the etiology being related to AD or vascular pathology. The choice of combination of A.H.T. therapy should also consider the combination which would lead to an optimum benefit in slowing the progression of dementia. Additionally, our results underline a more complex A.D. disease model than previously thought, which opens new treatment options.
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