Cognitive Decline

The spectrum of cognitive decline in older adults ranges from normal cognitive decline with aging to subjective cognitive impairment to mild cognitive impairment (MCI) to dementia. ^[1] Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. ^[2] Dementia is an insidious, chronic and progressive loss of a previously acquired cognitive ability, and it is a major cause of death and disability in older adults. ^{[3] [4]}

Alzheimer's disease is the leading cause of dementia, with declines in episodic memory considered a hallmark that occurs early in disease progression. ^[4] Cerebrovascular dysfunction is a common etiology shared across dementia types, with small-vessel disease an underlying neuropathologic hallmark and mechanisms including hypoxia, oxidative stress, neuroinflammation and neurodegeneration contributing to disease progression. ^[5] Accumulated oxidative stress impairs mitochondrial function and is emerging as one of the key mechanisms causing cognitive aging and neurodegenerative diseases such as Alzheimer's disease. ^[6] Most patients with vascular dementia also have other pathology, most commonly Alzheimer disease, so mixed pathology is typical rather than a single pure cause. ^[7]

In a systematic review of 66 studies covering 242,804 participants, the overall worldwide prevalence of mild cognitive impairment in community dwellers aged 50 years and older was 15.56%, increasing with age and decreasing with education level. ^[8] In adults aged 65 years and older the prevalence of MCI is 10% to 20%, risk increases with age, and men appear to be at higher risk than women. ^[9] MCI is a risk state for dementia and more than half of people with MCI progress to dementia within 5 years, with the amnestic subtype carrying a high risk of progression to Alzheimer's disease. ^[2] At present no medications have proven effective for MCI, and clinicians should evaluate for reversible causes such as depression, polypharmacy and uncontrolled cardiovascular risk factors. ^{[9] [10]}

Around a third of dementia cases are attributable to modifiable risk factors such as physical inactivity, smoking and hypertension. ^[11] Current evidence supports aerobic exercise, mental activity and cardiovascular risk factor control in patients with MCI to help decrease the risk of further cognitive decline. ^[9] Lifestyle modification such as aerobic exercise is an approved modality to preserve cognitive ability and decrease the rate of progression to dementia. ^[1] Chronic elevation in blood pressure is a major risk factor for cognitive decline and loss of autonomy later in life, and lowering blood pressure benefits older hypertensive subjects even after the age of 80 years. ^[12]