Changes in the Brain

In persons who do not have neurologic disease, intellectual performance tends to be maintained until at least age 80. However, tasks may take longer to perform because of some slowing in central processing. Verbal skills are well maintained until age 70, after which, some healthy elderly persons gradually develop a reduction in vocabulary, a tendency to make semantic errors, and abnormal prosody. Other age-related changes in mentation are subtle but can be detected as difficulty learning, especially languages, and forgetfulness in noncritical areas. However, this mild forgetfulness is unlike dementia in that it does not impair recall of important memories or affect function.

The elderly, particularly those with some degree of neurologic disease, are especially susceptible to the actions of drugs. Hypnotics, which may be effective and safe for most persons, may cause confusion or delirium in the elderly. Stress due to medical or psychologic disorders can worsen even minimal brain disease. Depression often produces a dementia-like syndrome (pseudodementia) in elderly persons. New onset of seizures is uncommon in the elderly. The causes of seizures in the elderly are listed in Table 42-1.

Loss of nerve cells: With normal aging, the number of nerve cells in the brain decreases. Cell loss is minimal in some areas (eg, brain stem nuclei, supraoptic and paraventricular nuclei) but is as great as 10 to 60% in others (eg, hippocampus). Loss also varies within the cortex (eg, loss is 55% in the superior temporal gyrus but 10 to 35% in the tip of the temporal lobe).

From age 20 or 30 to age 90, brain weight declines about 10%, and the area of the cerebral ventricles relative to the entire brain (as seen on cross section in the coronal view) may increase three to four times. The clinical effects of these changes are difficult to determine because brain weight and ventricular size may not correlate with intelligence; indeed, severe dementia may occur in persons who have normal ventricular size for their age.

Histologic changes: With normal aging, the pigment lipofuscin is deposited in nerve cells, and amyloid in blood vessels. Also, senile plaques and, less frequently, neurofibrillary tangles occur in elderly persons even without clinical evidence of dementia (in Alzheimer's disease, plaques and tangles occur in much greater numbers).

Accumulation of free radicals: Free radicals (atoms or molecules with one unpaired electron), which are produced normally during metabolism, accumulate with age and may have a toxic effect on certain nerve cells.

Changes in neurotransmitter systems: With normal aging, changes in neurotransmitter systems (enzymes, receptors, and neurotransmitters) occur (see Table 42-2). For example, choline O-acetyltransferase levels tend to decrease; the number of cholinergic receptors tends to decrease; and g-aminobutyric acid, serotonin, and catecholamine levels usually decrease. Choline O-acetyltransferase levels and dopamine levels may further decrease in Alzheimer's disease and in Parkinson's disease, respectively. Another age-related change is an increase in monoamine oxidase levels. When this increase is inhibited by monoamine oxidase inhibitors, onset of disability in patients with Parkinson's disease may be forestalled.

Decreased cerebral blood flow: With normal aging, cerebral blood flow decreases by about 20% on average; decreases are even greater in persons with small-vessel cerebrovascular disease due to diabetes and hypertension. Although blood flow in women is usually greater than in men until age 60, the subsequent rate of decrease is slightly more rapid. Decreases are greater in certain areas of the brain (eg, the prefrontal region) and are greater in gray matter than in white matter.

Compensatory mechanisms: Certain properties of the brain may reduce the clinical effects of age-related changes. Redundancy is a property whereby more nerve cells exist than are needed. For example, diabetes insipidus (due to a lack of antidiuretic hormone) does not appear until > 85% of the nerve cells in the supraoptic and paraventricular nuclei have been destroyed. Furthermore, hydrocephalic patients, who have only a thin cerebral cortical mantle, may have normal intelligence. The number of cells required for certain functions is unknown, so the extent of redundancy is difficult to estimate. However, redundancy probably reduces the effects of age-related neuron loss.

Plasticity at the nerve cell level involves compensatory lengthening and production of dendrites in remaining nerve cells to offset the age-related gradual deterioration and loss of nerve cells. New connections in the dendritic tree may compensate for the fewer nerve cells. Plasticity in the dendritic tree may also occur in Alzheimer's disease, perhaps as a biologic attempt to preserve function.

Other compensatory mechanisms may occur when the brain is damaged. For example, the nondominant hemisphere may compensate when speech centers in the dominant hemisphere are damaged, leading to gradual improvement in speech function. Other motor systems may compensate when large areas of the cerebellum are destroyed by injury, vascular disease, or tumor, often leading to functional recovery. Compensatory mechanisms are more effective in the higher centers. For example, the brain has a greater ability to compensate after injury than does the spinal cord, but the ability to compensate declines with age. The spinal cord does not have the redundancy of the brain to compensate for cell damage.