The effect of HMG-CoA reductase inhibitors on cognition in patients with alzheimer's dementia: A prospective withdrawal and rechallenge pilot study

Kalpana P. Padala, Prasad R. Padala, Dennis P. McNeilly, Jenenne A Geske, Dennis H. Sullivan, Jane Frances Potter

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background: Statins are well-known for their cardiovascular benefits. However, the cognitive effects of statins are not well understood. We hypothesized that individuals with preexisting dementia would be more vulnerable to statin-related cognitive effects. Objective: The aim of this study was to evaluate the impact on cognition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) discontinuation and rechallenge in individuals with Alzheimer's dementia (AD) on statins at baseline. Methods: A 12-week prospective, open-label study was conducted in a geriatric clinic setting. Eighteen older subjects underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE); secondary outcome measures were the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and fasting cholesterol. The change in outcome measures was assessed using repeated-measures ANOVA and paired t tests. Results: At the end of the intervention, there was a significant difference across time for MMSE score (P = 0.018), and total cholesterol (P = 0.0002) and a trend toward change across time for ADL (P = 0.07) and IADL (P = 0.06) scale scores. Further analyses using paired t tests indicated improvement in MMSE scores (Δ1.9 [3.0], P = 0.014) with discontinuation of statins and a decrease in MMSE scores (Δ1.9 [2.7], P = 0.007) after rechallenge. Total cholesterol increased with statin discontinuation (P = 0.0003) and decreased with rechallenge (P = 0.0007). The CERAD score did not show a change across time (P = 0.31). There was a trend toward improvement in ADL (P = 0.07) and IADL (P = 0.06) scale scores with discontinuation of statins, but no change with rechallenge. Conclusions: This pilot study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. Statins may adversely affect cognition in patients with dementia.

Original languageEnglish (US)
Pages (from-to)296-302
Number of pages7
JournalAmerican Journal of Geriatric Pharmacotherapy
Volume10
Issue number5
DOIs
StatePublished - Oct 1 2012

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cognition
Alzheimer Disease
Activities of Daily Living
Cholesterol
Outcome Assessment (Health Care)
Dementia
Registries
compound A 12
Geriatrics
Fasting
Analysis of Variance
Oxidoreductases

Keywords

  • Alzheimer's dementia
  • cognition
  • statins

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Pharmacology (medical)

Cite this

The effect of HMG-CoA reductase inhibitors on cognition in patients with alzheimer's dementia : A prospective withdrawal and rechallenge pilot study. / Padala, Kalpana P.; Padala, Prasad R.; McNeilly, Dennis P.; Geske, Jenenne A; Sullivan, Dennis H.; Potter, Jane Frances.

In: American Journal of Geriatric Pharmacotherapy, Vol. 10, No. 5, 01.10.2012, p. 296-302.

Research output: Contribution to journalArticle

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abstract = "Background: Statins are well-known for their cardiovascular benefits. However, the cognitive effects of statins are not well understood. We hypothesized that individuals with preexisting dementia would be more vulnerable to statin-related cognitive effects. Objective: The aim of this study was to evaluate the impact on cognition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) discontinuation and rechallenge in individuals with Alzheimer's dementia (AD) on statins at baseline. Methods: A 12-week prospective, open-label study was conducted in a geriatric clinic setting. Eighteen older subjects underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE); secondary outcome measures were the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and fasting cholesterol. The change in outcome measures was assessed using repeated-measures ANOVA and paired t tests. Results: At the end of the intervention, there was a significant difference across time for MMSE score (P = 0.018), and total cholesterol (P = 0.0002) and a trend toward change across time for ADL (P = 0.07) and IADL (P = 0.06) scale scores. Further analyses using paired t tests indicated improvement in MMSE scores (Δ1.9 [3.0], P = 0.014) with discontinuation of statins and a decrease in MMSE scores (Δ1.9 [2.7], P = 0.007) after rechallenge. Total cholesterol increased with statin discontinuation (P = 0.0003) and decreased with rechallenge (P = 0.0007). The CERAD score did not show a change across time (P = 0.31). There was a trend toward improvement in ADL (P = 0.07) and IADL (P = 0.06) scale scores with discontinuation of statins, but no change with rechallenge. Conclusions: This pilot study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. Statins may adversely affect cognition in patients with dementia.",
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T2 - A prospective withdrawal and rechallenge pilot study

AU - Padala, Kalpana P.

AU - Padala, Prasad R.

AU - McNeilly, Dennis P.

AU - Geske, Jenenne A

AU - Sullivan, Dennis H.

AU - Potter, Jane Frances

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N2 - Background: Statins are well-known for their cardiovascular benefits. However, the cognitive effects of statins are not well understood. We hypothesized that individuals with preexisting dementia would be more vulnerable to statin-related cognitive effects. Objective: The aim of this study was to evaluate the impact on cognition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) discontinuation and rechallenge in individuals with Alzheimer's dementia (AD) on statins at baseline. Methods: A 12-week prospective, open-label study was conducted in a geriatric clinic setting. Eighteen older subjects underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE); secondary outcome measures were the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and fasting cholesterol. The change in outcome measures was assessed using repeated-measures ANOVA and paired t tests. Results: At the end of the intervention, there was a significant difference across time for MMSE score (P = 0.018), and total cholesterol (P = 0.0002) and a trend toward change across time for ADL (P = 0.07) and IADL (P = 0.06) scale scores. Further analyses using paired t tests indicated improvement in MMSE scores (Δ1.9 [3.0], P = 0.014) with discontinuation of statins and a decrease in MMSE scores (Δ1.9 [2.7], P = 0.007) after rechallenge. Total cholesterol increased with statin discontinuation (P = 0.0003) and decreased with rechallenge (P = 0.0007). The CERAD score did not show a change across time (P = 0.31). There was a trend toward improvement in ADL (P = 0.07) and IADL (P = 0.06) scale scores with discontinuation of statins, but no change with rechallenge. Conclusions: This pilot study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. Statins may adversely affect cognition in patients with dementia.

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