ADCLT 2005.
| Methods | Randomised controlled trial | |
| Participants | 63 participants (32 intervention, 31 control) with probable or possible AD (NINCDS‐ADRDA and DSM‐IV guidelines), 9th grade education or equivalent, speak English fluently and of good general health as evidenced by physical, neurological and clinical laboratory examination. Aged ≥ 51 years, mean (± SD) 78.9 ± 1.2 years in placebo group, 78.15 ± 1.3 years in atorvastatin group. MMSE 12‐28, score ≤ 4 on the modified Hachinski scale and ≤ 20 on the GDS. Individuals were allowed to continue stable dose use of cholinesterase inhibitor and medications treating non‐excluded medical conditions. Patients recruited from a single site in the USA Duration of study: 1 year Mean (± SD) total cholesterol at entry was 208.00 ± 6.41 mg/dL (5.39 ± 0.17 mmol/L) in the placebo group and 207.97 ± 5.98 mg/dL (5.39 ± 0.15 mmol/L) in the atorvastatin group, mean (± SD) LDL‐C 122.22 ± 6.19 mg/dL (3.16 ± 0.16 mmol/L) and 124.47 ± 5.92 mg/dL (3.22 ± 0.15 mmol/L), mean (± SD) VLDL‐C 26.65 ± 2.26 mg/dL in the placebo group and 27.84 ± 2.13 mg/dL in the atorvastatin group (to convert total cholesterol from mg/dL to mmol/L, multiply by 0.0259; LDL‐C mg/dL to mmol/L, multiply by 0.02586) |
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| Interventions | Intervention: atorvastatin 80 mg daily Control: matching placebo |
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| Outcomes | Primary outcomes: change in ADAS‐Cog and CGIC Secondary outcomes: change in MMSE, NPI Caregiver Distress Scale, GDS, ADCS‐ADL |
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| Notes | Participants were excluded with a neurological or psychiatric disease other than AD, including suspected Parkinson's disease or dementia with Lewy bodies, significant systemic illness, organ failure, myocardial infarction, cardiac or thromboembolic vascular disease, major depression according to DSM‐IV criteria, current anticholinergic use. Individuals with a history of head injury; significant liver disease or elevated transaminase levels, or both; allergy to statin medication or screen cholesterol levels < 2.3 mmol/L were also excluded. No participant was using memantine or allowed to initiate cholinesterase inhibitor use after trial entrance and continue participation | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation was performed in blocks of 10 (5 active medication and 5 placebo) using an Excel spreadsheet random number generator Comment: probably done |
| Allocation concealment (selection bias) | Low risk | The sequence was inspected to ensure there was no duplication of random sequences and that there were 5 individuals assigned to each treatment group Comment: probably done |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | All investigators were blinded to both treatment groups and cholesterol profiles after randomisation. Only the physician safety monitor, who was not involved in any other aspect of the trial, viewed quarterly cholesterol levels to ensure patient safety. Bottles of study medication were coded at the pharmacy. Atorvastatin calcium tablets, 40 mg, and identical placebo tablets were supplied in bulk by Pfizer Pharmaceuticals, Inc. Bottles of study medication were coded at the pharmacy according to the randomisation schedule, transmitted to the clinic and thereafter provided to the participant/carer Comment: probably done |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Double blind Comment: probably done |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Flow table provided detailing flow of participants through the study. 29 active treatment and 27 placebo patients evaluated at visit 2, 26 active treatment and 22 placebo evaluated at visit 3 and 25 active treatment and 21 placebo patients evaluated at visit 4. Reasons for drop‐out not given |
| Selective reporting (reporting bias) | Low risk | Change in cognitive scales as detailed in methods section provided |