Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!

This chapter addresses the following Geriatric Fellowship Curriculum Milestone: #9


Learning Objectives

  • Understand how aging affects the brain at the histologic, cellular, and molecular levels and how these changes are linked to cognitive decline and common neurodegenerative diseases.

  • Gain a clear understanding of the most prominent biochemical and molecular aspects of the aging brain.

  • Learn about the effects of aging on cognition and neurodegenerative diseases.

  • Recognize novel active areas of research in the field of cognitive neuroscience.

  • Learn how environmental factors influence normal brain aging.

Key Clinical Points

  1. Given the steady increase in average human lifespan, the number of individuals who will experience some degree of cognitive decline is rising.

  2. Healthy aging is associated with atrophy of the gray matter; however, it is not indicative of presence of a disease.

  3. Comprehensive clinical evaluation is necessary to differentiate mild cognitive impairment and dementia from normal aging-associated cognitive decline.

  4. Specific aging-associated histologic, cellular, and molecular changes can predispose to neurodegenerative diseases.

  5. Environmental factors can be modified to mitigate potential effects of aging on brain functions.

Many cellular and molecular aspects of brain aging are shared with other organ systems, including increased oxidative damage to proteins, nucleic acids and membrane lipids, impaired energy metabolism, and the accumulation of intracellular and extracellular protein aggregates. However, given the molecular and structural complexity of neural cells that express approximately 50 to 100 times more genes than cells in other tissues, there are age-related changes that are unique to the nervous system. For example, complex cellular signal transduction pathways involving neurotransmitters, trophic factors, and cytokines that are involved in regulating neuronal excitability and plasticity are subject to modification by aging. This chapter describes cellular and molecular changes that occur in the brain during aging and how such changes may predispose to neurodegenerative diseases.


A large segment of the world population will experience some degree of cognitive decline during aging (Figure 62-1). This decline most typically affects working memory as well as short-term and delayed memory recall; however, a smaller group of individuals will also experience reduced information processing speed and spatial memory. Most of the decline appears to occur after the age of 60 with minimal or nonexistent changes occurring between the age of 20 and 60. Functional magnetic resonance imaging and positron emission tomography studies suggest that the cognitive decline might be linked to the progressive reduction in the volume of specialized memory-forming and -processing brain areas (Figure 62-2). Similar age-associated changes have also been observed in nonhuman primates, dogs, rats, and mice, suggesting intrinsic age-associated events. Nonmedical interventions, such as physical exercise, cognitive stimulation, and diet together with treatment of common medical comorbidities, such as obesity, hypertension, hypercholesterolemia, diabetes, and metabolic/hormonal imbalances might help mitigate age-associated declines.

FIGURE 62-1.

Cognitive changes as a result of aging. Trends of normal ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.