Cognitive Aging Progress in Understanding and Opportunities for Action (2015) / Chapter Skim
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4B Risk and Protective Factors and Interventions: Health and Medical Factors
4B Risk and Protective Factors and Interventions: Health and Medical Factors
Pages 149-186
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From page 149... ...
This chapter addresses many of the external factors and comorbidities that may affect cognition. The basic overall challenge is that much more needs to be learned about how these factors affect cognitive aging -- in particular, whether they have long-term effects on cognitive function.
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Evidence from Observational Studies Although a number of studies have indicated that there may be an association between these drug classes and dementia, the potential for unrecognized dementia or other confounding conditions in many of these studies prevents the establishment of any causal relationship. Beers Criteria Medications Based on a comprehensive and systematic review and a guideline panel process which included the grading of evidence and a public comment period, the 2012 American Geriatrics Society's (AGS's)
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A clinical review of 27 studies that included anticholinergic assays and measurement of cognitive performance found that 25 showed associations between the anticholinergic activity of medications and delirium, cognitive impairment, or dementia (Campbell et al., 2009)
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are associated with a markedly increased risk for delirium, cognitive impairment, falls, fractures, and motor vehicle accidents (Billioti de Gage et al., 2012; de Vries et al., 2013)
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TABLE 4B-2 Drugs with Strong Anticholinergic Properties Antimuscarinics (urinary Antiparkinson Skeletal Muscle Antihistamines Antidepressants incontinence) Agents Antipsychotics Antispasmodics Relaxants Brompheniramine Amitriptyline Darifenacin Benztropine Chlorpromazine Atropine products Carisoprodol Carbinoxamine Amoxapine Fesoterodine Trihexyphenidyl Clozapine Belladonna alkaloids Cyclobenzaprine Chlorpheniramine Clomipramine Flavoxate Fluphenazine Dicvclomine Orphenadrine Clemastine Desipramine Oxybutynin Loxapine Homatropine Tizanidine Cyproheptadine Doxepin Solifenacin Olanzapine Hyoscyamine products Dimenhydrinate Imipramine Tolterodine Perphenazine Propantheline Diphenhydramine Nortriptyline Trospium Pimozide Scopolamine Hydroxyzine Trimipramine Prochlorperazine Loratadine Promethazine Meclizine Thioridazine Thiothixene Trifluoperazine SOURCE: AGS, 2012.
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. A systematic review of the impact of anticholinergic discontinuation on cognitive outcomes in older adults by Salahudeen and colleagues (2014)
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However, because of various methodological, clinical, and ethical issues, there has as yet been no research establishing the impact of these initiatives on sustaining or improving cognition. Determining the impact of these medications on cognitive aging will require carefully conducted longitudinal studies.
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, there are many unknowns concerning the extent to which prevention and treatment efforts lead to improvements in cognitive health and how these efforts affect cognitive aging over the life span. For example, reducing the occurrence of strokes will be beneficial to cognitive health; however, much remains to be learned about the effects on cognitive function of treating the individual risk factors for stroke such as hyperlipidemia.
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and has been identified in systematic reviews as an important potentially preventable risk factor for cognitive decline and dementia with an increased hazard ratio of between 1.24 and 1.59, depending on the study (Etgen et al., 2011)
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will monitor the course of cognitive decline in people undergoing intensive blood pressure control. Summary Although the evidence from clinical trials does not demonstrate a clear cognitive benefit from hypertension treatment and the long-term impact on cognitive aging is not known, the benefits for preventing heart attack and stroke, both of which are linked to cognitive decline, are evident.
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, including the Heart Protection Study and the PROSPER trial (Prospective Study of Pravastatin in the Elderly at Risk) , have failed to demonstrate a protective effect of statin treatment on cognitive functioning (McGuinness et al., 2009)
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. Consistent with these studies, a 2010 systematic review of clinical trials of the treatment of cardiovascular risk factors to prevent cognitive decline concluded that there is no apparent cognitive benefit from treating hyperlipidemia and that the treatment of hypertension has only a suggestive effect on cognitive decline (Ligthart et al., 2010)
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. In preliminary trials, long-acting intranasal insulin has shown promise in improving cognitive function in adults with mild cognitive impairment (MCI)
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and through the complications of obesity, such as obstructive sleep apnea, obesity may also increase risk of cognitive aging directly through the presence of excess adipose tissue and the secretion of inflammatory proteins such as leptin, which have been linked to cognitive impairment and decline (Gustafson, 2012; Holden et al., 2009; Zeki Al Hazzouri et al., 2013)
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. Another study of 225 cardiac surgery patients age 60 years and older demonstrated that delirium is independently associated with cognitive decline at 1 year postsurgery; the time pattern of cognitive functioning showed an initially steep decline followed by improvement but with residual impairment (Saczynski et al., 2012)
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Authoritative guidelines and systematic reviews recommend multicomponent, non-pharmacologic intervention strategies targeted toward patients with delirium risk factors and implemented by skilled interdisciplinary teams (Greer et al., 2011; O'Mahony et al., 2011)
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. More needs to be learned about the long-term impacts of delirium on cognitive aging.
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For each condition, little is known about how the medical condition might or might not affect cognitive aging. Thyroid Disorders Both hypo- and hyperthyroidism have been long identified as major reversible causes of cognitive decline and are screened for in many cases of cognitive impairment.
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A recent systematic review and meta-analysis involving seven cross-sectional and 10 prospective studies with more than 54,000 participants who were pre-dialysis but with mild to severe renal impairment demonstrated an increased relative risk for cognitive decline of 1.65 (95% CI 1.32–2.05)
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Nonetheless, a recent systematic review supported a strong relationship between late-life depression and subsequent dementia, with the strongest risk for vascular dementia. A meta-analysis of 23 population-based studies examining late-life depression and involving more than 49,000 people demonstrated a significantly increased risk for all-cause dementia (RR 1.85, 95% CI 1.67–2.04)
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. However, one systematic review found chronic cognitive impairment in mild TBI patients to have occurred only among those who had complications in their clinical course (Godbolt et al., 2014)
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. Some types of visual impairment, such as decreased near vision, may be risk factors for cognitive impairment (Reyes-Ortiz et al., 2005)
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SLEEP Evidence from Observational Studies Epidemiological studies of self-reported sleep quality have generally shown an association among poorer cognitive function, insomnia symptoms, and poor sleep quality (Fortier-Brochu et al., 2012; Schmutte et al., 2007) , although the results of studies evaluating cognitive impairment and sleep patterns have been mixed.
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Sleep disordered breathing is a promising modifiable risk factor for improving cognitive outcomes; however, the timing and duration of its treatment as well as the optimal treatment population are still unclear. A meta-analysis of 13 treatment studies found improvements in attention, but most trials were short-term and underpowered (a mean sample size of 54)
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The mainstay of current treatment for obstructive sleep apnea consists of non-pharmacologic approaches, including CPAP and weight reduction. GENETIC FACTORS: APOE STATUS Advances in genetics and molecular biology have prompted substantial exploration of a possible genetic basis for age-related cognitive impairment.
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. Summary Overall, it appears that while genetic forces must be ultimately important in cognitive aging, the research is at an early stage, the particular genes and related mechanisms have not been identified, and the research quest continues.
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American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society 60(4)
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2008. A comparison of cognitive functioning in older adults with and without traumatic brain injury.
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2015. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia.
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2012. Chronic kidney disease and cognitive impairment: A systematic review and meta-analysis.
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2014. Systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury: Results of the International Col laboration on Mild Traumatic Brain Injury Prognosis.
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Journal of the American Geriatrics Society 48(12)
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2010. Treatment of cardiovascular risk factors to prevent cognitive decline and dementia: A systematic review.
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2009. Blood pressure lowering in pa tients without prior cerebrovascular disease for prevention of cognitive impairment and dementia.
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2013. Statins and cognitive function: A systematic review.
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2007. The relation between cognitive functioning and self-reported sleep complaints in nondemented older adults: Results from the Bronx Aging Study.
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2013. Statins and cognitive decline in older adults with normal cognition or mild cognitive impairment.
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2011. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women.
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