As the quest to cure dementia continues, lifestyle modification is an emerging strategy to prevent or modify the dementia process. With the number of individuals with dementia expected to increase from 47 million in 2015 to 66 million by 2030, preventing or delaying the onset of dementia may reduce the global burden.
One-third of risk factors for dementia are potentially modifiable, including education in early life; hearing loss, hypertension, and obesity in midlife (45–65 years); and smoking, depression, physical activity, social engagement, and diabetes mellitus in late life.
Longitudinal studies have provided intriguing results on the effect of lifestyle factors on the dementia process. Vascular risk factors in midlife, when people are more likely to be asymptomatic, may be critical in the development of an underlying dementia process, including Alzheimer disease (AD).
An elevated body mass index (BMI ≥30 kg/m2) at midlife was associated with twofold increased odds of elevated brain amyloid deposition in late life. Increased brain amyloid deposition in late life was also associated with the number of midlife vascular risk factors (body-mass index, smoking history, hypertension, diabetes, and high cholesterol); the adjusted odds ratio for ≥2 risk factors versus no risk factors was 2.88 in the entire cohort and 9.15 in apolipoprotein E ℇ4 carriers. Late-life vascular risk factors were not associated with increased brain amyloid deposition in late life
Vascular risk factors for dementia also may be influenced by gender. With hypertension defined as a blood pressure of ≥140/90 mm Hg and dementia diagnoses determined by inpatient and outpatient diagnostic codes, women with midlife hypertension had a 65% increased dementia risk compared with normotensive women, but the association did not hold in men.
For women, compared with those who remained normotensive, a change to hypertension status and persistent hypertension from early to mid-adulthood were associated with a 73% and 63% increased risk for dementia, respectively. Hypertensive females who remitted to normotensive status did not have an increased dementia risk. Changes in hypertension status did not affect dementia risk in men.
Lifestyle factors also may contribute to incident mild cognitive impairment (MCI). In six low- and middle-income countries in the World Health Organization’s Study on Global Aging and Adult Health, a diagnosis of MCI was associated with 28% increased odds of not meeting recommended physical activity criteria of 150 minutes of moderate-to-vigorous physical activity per week.
Preliminary data show that aerobic exercise with three 1-hour sessions a week for 6 months may lead to short-term improvements in general cognitive performance, general cardiovascular capacity, and resting diastolic blood pressure in patients with vascular cognitive impairment. A target systolic blood pressure of <120 mm Hg may also improve cognition, particularly in black people.
In late life, mentally stimulating activities such as craft activities, computer use, and social activities were associated with a 25% reduction in risk for amnestic MCI in cognitively normal individuals (median baseline age, 77 years); computer use was also associated with decreased risk for nonamnestic MCI. The lowest MCI risk was seen in apolipoprotein E ℇ4 noncarriers who performed mentally stimulating exercises (except for craft activities), and the highest MCI risk was seen in apolipoprotein E ℇ4 carriers who did not perform mentally stimulating activities.
Cross-sectional studies using neuroimaging and cognitive testing more directly inform the relationship between lifestyle factors and brain health. Low adherence to the Mediterranean diet was associated with a significantly larger decrease in total brain volume in older adults after adjusting for age, sex, body-mass index, medical comorbidities, education, intellectual abilities, cognitive performance, and apolipoprotein E ℇ4 carrier status
Lifestyle factors may influence AD biomarkers. People with hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure (CHF), diabetes mellitus, or stroke had greater neurodegeneration identified by MRI and fluorodeoxyglucose positron emission tomography (PET) compared with those without vascular or metabolic conditions.
Although cerebral amyloid deposition (based on Pittsburgh Compound B [PiB] PET) and entorhinal cortex tau uptake (based on tau-PET) were not different between those with and without vascular or metabolic conditions, hyperlipidemia was associated with entorhinal cortex tau uptake; and diabetes mellitus, CHF, and cardiac arrhythmias were associated with neurodegeneration.
The Dominantly Inherited Alzheimer’s Disease study showed changes in AD biomarkers among presymptomatic AD mutation carriers with low versus high exercise level (<150 minutes/week vs. more). The exercise groups did not differ in cerebral amyloid load (based on PiB-PET), cerebrospinal fluid (CSF) amyloid-beta 42 level, or CSF tau level. However, in presymptomatic mutation carriers who already had amyloid pathology, higher cerebral amyloid levels were seen in the low-exercise group than in the high-exercise group.
The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability used a multidomain lifestyle intervention in participants aged 60 to 77 years who had an increased risk for dementia later in life and cognitive abilities at the mean or slightly lower than expected for age.
The control group received information and advice on lifestyle modification. The intervention group received additional training on nutrition, exercise, cognition, and management of vascular risk factors (hypertension, dyslipidemia, and diabetes).
After 24 months, the intervention group showed improvements in total cognitive scores, executive functioning, and processing speed compared with the control group, even after accounting for sociodemographic factors, socioeconomic status, baseline cognition, cardiovascular risk factors, and cardiovascular comorbidity at baseline.
