A 70-year-old man has a history of inferior myocardial infarction at age 57 years, percutaneous coronary intervention, type 2 diabetes mellitus, and hypertension. He comes to the clinic for routine follow-up. His mother recently died at the age of 90 years after a long battle with dementia. Today, he wants to know what he can do to decrease his risk of developing dementia.
He denies any chest pain, shortness of breath, or palpitations with activity, although the most exercise he gets in a day includes walking up the five steps in his home, as well as walking across a parking lot or around the grocery store. He lives alone and does not enjoy cooking; therefore, he frequently eats frozen dinners or fast food.
Metoprolol succinate 50 mg po daily
Lisinopril 10 mg po daily
Metformin 500 mg po bid
Aspirin 81 mg po daily
Atorvastatin 40 mg po qhs
Physical Examination: Vital Signs: Afebrile, heart rate 60 bpm in sinus rhythm, blood pressure (BP) 155/96 mm Hg, oxygen saturation of 95% on room air, body mass index is 31. General: Obese man in no acute distress. Cardiovascular: Regular rate and rhythm, no murmurs, rubs, or gallops; jugular venous pressure is normal. Respiratory: Lungs are clear to auscultation bilaterally. Abdomen: Obese, soft, non-tender, non-distended with normal active bowel sounds. Extremities: No edema, warm, well perfused.
Hemoglobin A1c was 9% two months ago.
His last echocardiogram was one year ago and showed overall normal left ventricular systolic function with mild hypokinesis of the inferior wall.
His electrocardiogram today shows normal sinus rhythm, rate 60 bpm with no q waves, normal axis.
Which of the following statements describes the advice you should give him as his cardiologist?
The correct answer is: D. Improve his diet, start exercising, improve his diabetes and BP control, and continue taking his atorvastatin.
Improved diet and exercise and good management of vascular disease risk factors have all been implicated in the prevention or delayed onset of cognitive decline.
Currently, cognitive training is difficult to implement clinically as what counts as "cognitive rehabilitation" or "cognitive training" varies significantly from study to study. There are mixed data regarding the effectiveness of cognitive rehabilitation/training/exercises on preventing dementia or on treating prevalent dementia, as the majority of existing studies are small. One meta-analysis of seven randomized clinical trials did find a protective effect of cognitive exercises on subsequent cognitive ability,1 and cognitive training paired with a diet and exercise intervention as well as vascular risk factor monitoring also decreased the incidence of dementia.2 The authors do not view this option as the single best answer because cognitive training is outside the scope of the typical cardiologist's practice and is likely more effective when implemented alongside lifestyle changes and optimal cardiovascular risk factor management.
Randomized clinical trial data of pharmacologic interventions have been limited to populations with cognitive impairment or dementia and have shown mixed results.3,4 Based on current data, the American Heart Association (AHA)/American Stroke Association (ASA) statement on vascular contributions to cognitive impairment and dementia recommends donepezil or galantamine for cognitive enhancement in patients with vascular dementia or mixed Alzheimer disease/vascular dementia, respectively (both medications are a Class IIb, Level of Evidence A recommendation).4 Such therapy prescribed by a neurologist, geriatrician, or primary care doctor may be appropriate for this patient should he show evidence of cognitive impairment or dementia.
Management of Cardiovascular Risk Factors and Lifestyle Interventions
Observational studies demonstrated that systolic BP >140 mm Hg,5 diastolic BP >95 mm Hg,6 and total cholesterol >251 g/dL at mid-life were all associated with an increased risk of developing dementia later in life.5 Other studies have also demonstrated an increased risk for dementia in patients with diabetes and a linear increase in risk of incident dementia as glucose tolerance decreases in patients without a diagnosis of diabetes.7,8 Finally, prospective, observational data showed that patients with a body mass index >31 kg/m2 had a higher risk of dementia.5 Similarly, a high waist-to-hip ratio has also been associated with greater risk of dementia later in life.4 These data suggest weight loss as another strategy for minimizing dementia risk in overweight and obese individuals.
Statin usage, which is already indicated in our patient due to his diabetes and coronary artery disease,9 has also been associated with decreased incidence of dementia in observational studies,10 so this medication may be of even greater importance to this patient given his concern about his family history of dementia. Randomized controlled trials have not shown a protective benefit of statin therapy in patients with existing dementia. Existing randomized controlled trial data regarding primary prevention of cognitive decline have also been disappointing, but are limited to studies designed for primary cardiovascular outcomes and suffer from very low event rates and relatively short follow-up periods.10-12
Linking dietary habits to cognitive decline later in life is a challenging task because dietary habits are difficult to study and there are many potentially confounding variables. The 2011 AHA/ASA statement on vascular contributions to cognitive decline noted that omega-3 fatty acids and the Mediterranean diet have the most data supporting their role in preventing cognitive decline.4 Similarly, a recent systematic review noted the most evidence supporting a Mediterranean diet in the prevention or delay of cognitive decline and dementia.13 Antioxidants (vitamins C and E, beta-carotene), vitamin D, folic acid, vitamin B12, and vitamin B6 are other nutritional targets of interest; however, data do not strongly support their role in preventing cognitive decline thus far.4
Exercise has also been proposed as a potential preventive measure or treatment for cognitive decline. Potential mechanisms include increased blood flow to the brain, brain neurotrophins, and brain plasticity.4,14 Similar to diet, linking exercise to preventing cognitive decline is difficult, although cross-sectional and longitudinal studies have linked cognitive ability and physical fitness level in otherwise healthy children and young adults.14 The type, intensity, and duration of exercise necessary to have beneficial effects on cognition are currently unknown factors.
Given this patient's history and concerns, the authors of this Patient Case Quiz would recommend that he follow a Mediterranean diet rich in omega-3 fatty acids and refer him to a dietitian to help him plan meals that he can easily prepare. The authors would also recommend he start doing regular exercise that he enjoys, using the 2012 societal guidelines for stable ischemic heart disease as a guide (30-60 minutes of moderate-intensity exercise is recommended five to seven days per week).15 We would emphasize the importance of these lifestyle changes not only as methods to decrease his risk for cognitive decline, but also in causing weight loss and improving his BP and diabetes control – all of which may also help prevent cognitive decline. If lifestyle intervention is not adequate for BP or diabetes control, the authors would also increase his lisinopril, targeting BP <150/90 mm Hg16 and encourage him to talk with his primary care provider about better diabetes control.
Valenzuela M, Sachdev P. Can cognitive exercise prevent the onset of dementia? Systematic review of randomized clinical trials with longitudinal follow-up. Am J Geriatr Psychiatry 2012;17:179-87.
Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet 2015;385:2255-63
Cooper C, Li R, Lyketsos C, Livingston G. Treatment for mild cognitive impairment: systematic review. Br J Psychiatry 2013;203:255-64.
Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:2672-713.
Kivipelto M, Helkala E-L, Laakso MP, et al. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 2002;137:149-155.
Launer LJ, Ross GW, Petrovitch H, et al. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging 2000;21:49-55.
Ahtiluoto S, Polvikoski T, Peltonen M, et al. Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology 2010;75:1195-202.
Ohara T, Doi Y, Ninomiya T, et al. Glucose tolerance status and risk of dementia in the community: the Hisayama study. Neurology 2011;77:1126-34.
Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889-934.
Wanamaker BL, Swiger KJ, Blumenthal RS, Martin SS. Cholesterol, statins, and dementia: what the cardiologist should know. Clin Cardiol 2015;38:243-50.
Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo- controlled trial. Lancet 2005;360:7-22.
Trompet S, Vliet P, Craen AJM, et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol. 2009;257:85-90.
van de Rest O, Berendsen AA, Haveman-Nies A, de Groot LC. Dietary patterns, cognitive decline, and dementia: a systematic review. Adv Nutr 2015;6:154-68.
Qaseem A, Fihn SD, Dallas P, et al. Management of stable ischemic heart disease: summary of a clinical practice guideline from the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons. Ann Intern Med 2012;157:735-43.
James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA 2014;311:507.