We read the interesting observational study of Cramer et al. regarding statin therapy and the incidence of cognitive impairment without dementia and dementia in an elderly Mexican-American population. [1] The authors conclude that statin users are half as likely to develop cognitive impairment or dementia over the five years of observation. However, the study suggests that higher cholesterol levels actually protect subjects from cognitive impairment and dementia.
Baseline total cholesterol levels of statin-treated populations are higher than those of the general population. [2] Presumably, the cholesterol levels of the statin-treated patients in this study were higher than those of the non-statin treated patients. In the Framingham Heart Study cohort, subjects with total cholesterol levels more than 200 mg/dL, compared to those with levels less than 200 mg/dL, performed significantly better in cognitive measures including word fluency, attention, and concentration. The observation period in that study pre-dated the widespread use of statins. [3]
Moreover, an eight-year observational trial involving middle-aged women revealed that women with higher, low-density lipoprotein (LDL) cholesterol levels had a significantly better memory. [4] Interestingly, Cramer et al. found that baseline Modified Mini-Mental State Examination scores were significantly higher in statin users compared to statin non-users, suggesting a benefit from higher cholesterol levels.
Both lipophilic and hydrophilic statins promote oligodendrocyte lineage commitment by parenchymal glial progenitor cells in vitro. [5] If statins are taken for decades, it is possible that the homeostatic self-renewal of glial progenitor cells may be impaired resulting in cognitive decline. Therefore, statins may be detrimental over the long term by both lowering cholesterol levels and diminishing the glial progenitor cell pool.
Finally, we need long-term randomized prospective trials specifically designed to settle this important dispute. Regarding cholesterol and cognitive decline, perhaps more is better.
References
1. Cramer C, Haan MN, Galea S, et al. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 2008;71:344-350.
2. Thompson R, O’Regan C, Morant S, et al. Measurement of baseline total cholesterol: new data from The Health Improvement Network (THIN) database. Prim Care Cardiovasc J 2008;1:107-111.
3. Elias PK, Elias MF, D’Agostino RB, et al. Serum cholesterol and cognitive performance in the Framingham Heart Study. Psychosomatic Med 2005;67:24-30.
4. Henderson VW, Guthrie JR, Dennerstein L. Serum lipids and memory in a population based cohort of middle aged women. J Neurol Neurosurg Psychiatry 2003; 74: 1530-1535.
5. Sim FJ, Lang JK, Ali TA, et al. Statin treatment of adult human glial progenitors induces PPAR gamma-mediated oligodendrocytic differentiation. GLIA 2008;56:954-962.
We read the interesting observational study of Cramer et al. regarding statin therapy and the incidence of cognitive impairment without dementia and dementia in an elderly Mexican-American population. [1] The authors conclude that statin users are half as likely to develop cognitive impairment or dementia over the five years of observation. However, the study suggests that higher cholesterol levels actually protect subjects from cognitive impairment and dementia.
Baseline total cholesterol levels of statin-treated populations are higher than those of the general population. [2] Presumably, the cholesterol levels of the statin-treated patients in this study were higher than those of the non-statin treated patients. In the Framingham Heart Study cohort, subjects with total cholesterol levels more than 200 mg/dL, compared to those with levels less than 200 mg/dL, performed significantly better in cognitive measures including word fluency, attention, and concentration. The observation period in that study pre-dated the widespread use of statins. [3]
Moreover, an eight-year observational trial involving middle-aged women revealed that women with higher, low-density lipoprotein (LDL) cholesterol levels had a significantly better memory. [4] Interestingly, Cramer et al. found that baseline Modified Mini-Mental State Examination scores were significantly higher in statin users compared to statin non-users, suggesting a benefit from higher cholesterol levels.
Both lipophilic and hydrophilic statins promote oligodendrocyte lineage commitment by parenchymal glial progenitor cells in vitro. [5] If statins are taken for decades, it is possible that the homeostatic self-renewal of glial progenitor cells may be impaired resulting in cognitive decline. Therefore, statins may be detrimental over the long term by both lowering cholesterol levels and diminishing the glial progenitor cell pool.
Finally, we need long-term randomized prospective trials specifically designed to settle this important dispute. Regarding cholesterol and cognitive decline, perhaps more is better.
References
1. Cramer C, Haan MN, Galea S, et al. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 2008;71:344-350.
2. Thompson R, O’Regan C, Morant S, et al. Measurement of baseline total cholesterol: new data from The Health Improvement Network (THIN) database. Prim Care Cardiovasc J 2008;1:107-111.
3. Elias PK, Elias MF, D’Agostino RB, et al. Serum cholesterol and cognitive performance in the Framingham Heart Study. Psychosomatic Med 2005;67:24-30.
4. Henderson VW, Guthrie JR, Dennerstein L. Serum lipids and memory in a population based cohort of middle aged women. J Neurol Neurosurg Psychiatry 2003; 74: 1530-1535.
5. Sim FJ, Lang JK, Ali TA, et al. Statin treatment of adult human glial progenitors induces PPAR gamma-mediated oligodendrocytic differentiation. GLIA 2008;56:954-962.
Disclosure: The authors report no disclosures.