“Age does not depend upon years, but upon temperament and health. Some men are born old, and some never grow so.”

Tyron Edwards

“A man is as old as his arteries.”

Thomas Sydenham

The dogma that aging brings inevitable cognitive decline is being challenged by studies of the rapidly expanding oldest segment of our society, adults older than 60 years. Although some aspects of cognition are affected by aging, many changes in cognition previously considered the unavoidable consequence of brain senescence may instead result from incremental insults on brain function associated with aging-related medical conditions. The detection of such changes, which may stabilize or even reverse with appropriate intervention, and their differentiation from the cognitive changes associated with neurodegenerative disease or other neurological disorders is a critical task. The primary goal of this chapter is to describe changes in various cognitive abilities that occur with normal aging and with common age-related medical and neurological conditions.

General Intellectual Functioning

Intelligence is generally measured by summing the scores on a variety of verbal and performance subtests. Studies of aging have consistently shown that subtests measuring verbal abilities remain stable with normal aging. In contrast, subtests that require nonverbal creative thinking and new problem solving strategies show a slow decline with age. Crystallized abilities (information and skills gained from experience) remain relatively intact with aging, while fluid intelligence, which involves flexible reasoning and problem solving approaches, declines. Numerous studies have documented this general pattern in both cross-sectional and longitudinal research designs. Below, we review the literature on the effects of normal aging on specific cognitive functions (Table 62-1).

Attention

Attention involves the ability to focus on one or more pieces of information (auditory or visual) long enough to register and make meaningful use of the data. Attention requires both simple and complex immediate processing and provides a foundation for working memory and other cognitive functions. Sustained attention, or vigilance, entails attending to one type of information over a period of time. After controlling for reaction time and sensory changes, sustained attention and strategies for maintaining vigilance do not appear to change significantly with age. Divided attention, or the ability to concentrate on more than one piece of information at a time, may worsen with age, though research in this area has produced mixed results. Increased distractibility (difficulty blocking out irrelevant or salient stimuli), decreased use of effective strategies, and reduced processing speed may be responsible for some of the noted declines in divided attention. Pronounced impairment of attention is not typical of normal aging, however, and a complete evaluation of medical and psychosocial issues is warranted for individuals who demonstrate such changes. Attention can be negatively impacted by perceptual or sensory changes, illness, chronic pain, certain medications, and psychological disturbance (in particular, depression and anxiety), all of which are common in an older population. As the ability to effectively attend is a requisite for nearly all other cognitive functions, it is important to identify the cause/s of attentional impairment whenever possible and to implement any changes in medications or treatment that may help to resolve these problems.

Executive Functions

Executive functions include the ability to control and direct behavior, make meaningful inferences and appropriate judgments, plan and carry out tasks, manipulate multiple pieces of information at one time (working memory), complete complex motor sequences, and solve abstract and complex problems. Neuropsychological test performance on executive tasks declines slightly with age, and several current theories posit that deficits in working memory and executive function underlie many age-related changes in cognition. Neurocognitive tasks that require response inhibition, such as the Wisconsin Card Sort Test, Stroop Color–Word Test, and Brown–Peterson Distractor Test, may be affected.

Alternatively, many have suggested that a reduction in cognitive processing speed rather than executive function per se may be, at least in part, responsible for decreased performance on executive tasks. It should be noted that changes in the executive system that occur with normal aging are much less severe than the deficits associated with dysexecutive syndromes, including those caused by stroke, heavy and prolonged alcohol use, head injury, and some neurodegenerative diseases. In fact, successful aging appears to produce little impact on “real world” executive functions requiring planning and executing multiple tasks. Thus, it is important to assess an individual’s actual functional abilities in addition to performance on neuropsychological tests of executive function.

Memory

Memory changes are perhaps the most common cognitive complaints reported by older adults. Patients often wonder if their subjective concerns reflect normal age-related changes, or some pathological condition. For patients with a family history of Alzheimer’s disease or other dementia, even minor memory failings can cause significant anxiety. One of the difficulties in answering such questions lies in the complex nature of the memory process. Different forms of memory are invoked when learning new information (declarative memory), recalling prior life events (remote memory), recalling general knowledge not tied to a specific event (semantic memory), and remembering procedures for performing tasks such as riding a bicycle (procedural memory). In addition, some conditions result in modality-specific deficits, differentially affecting verbal or visual memory.

A number of models describe the different stages or processes involved in forming and recalling memories. One example, the modal model, describes memory processes in terms of sensory memory, short-term (working) memory, and long-term memory. First, when a patient senses and attends to a given stimulus, a large amount of information is briefly held in sensory memory. Information is then rehearsed or manipulated in short-term or working memory. Although many factors are involved in determining what information is transferred to long-term storage, sufficient rehearsal is a common requirement for successful transfer. Thus, it is clear that when a patient complains of memory changes, additional information is required to make sense of the problem.

Although it is true that some older adults continue to demonstrate memory performances comparable to young adults, on average even healthy older adults do show changes in some aspects of memory. For example, when a large group of healthy, nondemented elderly subjects was followed over a 7-year period, a general memory factor showed significant decline with time. Other studies have attempted to describe which aspects of memory change with healthy aging. In general, older adults without significant illness demonstrate increased difficulty learning new information compared to younger cohorts. When older adults are given repeated chances to practice learning new information, they demonstrate a slower learning curve and a lower total amount learned.

Although healthy older adults may retain slightly less information after a delay than do younger adults, this effect is less pronounced than the slowed learning rate. For delayed memory tests, patients are generally asked to recall information 15 to 60 minutes after the initial exposure. Although patients recall less information at the delay with age, they generally retain a stable proportion of the information that they initially learned. In general, longitudinal studies of aging show only small declines in delayed memory with age, particularly on tests of visual memory. Some older adults also appear less likely to use cognitive strategies to aid memory than younger subjects. This may be owing to generational differences in learning style. However, it may be significant because the use of memory strategies (i.e., grouping vegetables and clothing items for easier recall) reduces the age effect observed on free recall tests.

A number of memory processes do not appear to change with successful aging. Remote memory, that is recall of events that occurred in the distant past, remains relatively intact, as does sensory memory. In addition, while elderly patients often have medical problems that limit physical movement, procedural memory appears to be unaffected by healthy aging. Lastly, semantic memory, such as vocabulary and general information about the world, remains largely unchanged by aging until very late in life.

Longitudinal studies have consistently shown that as groups age, the variability in cognitive performance increases. Overall, studies of healthy aging suggest that there are some statistically significant declines in memory in late life. However, the memory functions of patients who age successfully are typically adequate for the demands of independent living.

Language

Language abilities incorporate multiple levels of processing, and general language functions tend to remain relatively stable with increasing age. Some linguistic abilities, however, particularly those involving language output, show reliable declines in older adults. As with other cognitive functions, there are multiple potential intervening factors, including trauma, illness, and sensory disruption, that may lead to more severe changes in the language functions.

Language Comprehension

Language comprehension involves discerning the simple and complex rules of language and incorporating both visual and auditory information into a meaningful concept; language comprehension is generally associated with few age-related impairments. The ability to recognize basic word structure and word representation is typically measured using “lexical-decision” tasks (in which letters are rapidly presented and the person is asked to identify whether or not it is a word), and simple word reading tasks. While some studies have suggested an inverse relationship between performance on these tasks and age, it is generally believed that such changes are the result of decreased reaction time and processing speed rather than the ability to comprehend word structure and meaning. In addition, there is some indication that the level of lexical processing changes slightly with age, in that older adults tend to rely more on word recognition than do younger adults, while ignoring other factors such as word length. Phonological understanding of language does not appear to change significantly with age, although hearing loss may appear to reduce auditory comprehension. Overall, it is generally accepted that language comprehension remains relatively intact throughout the lifespan.

Language Production

Basic syntactic abilities do not appear to change significantly with advancing age, although minor repetitions, longer pauses, and an increased use of pronouns and other vague words while speaking have been noted. Additionally, a recent longitudinal study suggests a decline in spoken grammatical complexity during the eighth decade of life. The authors note, however, that there is high interindividual variability throughout the lifespan in terms of syntactic aptitude.

Semantic abilities involve aptitude with naming and retrieving long-stored information. There is a steady increase in vocabulary knowledge throughout middle adulthood, and such knowledge typically remains stable in the later years. A frequent complaint from older adults, however, involves the “tip-of-the-tongue” phenomenon, in which there is a notable struggle with spontaneous word finding. In contrast to the dysnomia that often accompanies dementia, however, such changes appear to result primarily from difficulties retrieving rather than storing information, and thus there is usually a marked improvement when cues are given. Verbal fluency, the rate at which a person can spontaneously produce words belonging to a single phonemic or semantic category, also appears to change somewhat with age. Multiple research findings support a decrease in semantic fluency (“name all the animals you can”) while phonemic fluency (“tell me as many words as you can that begin with the letter F”) generally remains stable. In terms of strategy, it has been suggested that younger adults tend to produce more words and to change categories more frequently than do older adults on semantic fluency tasks, while older subjects generate the same amount of words but more “clusters” on tasks of phonemic fluency. Thus, older subjects likely rely more on structural word knowledge than on word meaning.

Visuospatial Skills

Visuospatial skills are commonly tested by constructional tasks in which patients are asked to draw figures or assemble objects. In general, as patients age, they become slower at completing visuospatial tasks. However, as noted, one of the more consistent findings in the field is that normal aging is associated with general slowing of psychomotor and cognitive speed. Therefore, performance on tests of visuospatial functioning is often confounded by slowing. Some studies have attempted to separate the effects of the two domains. For instance, after controlling for processing speed and executive functioning, the effects of age on the commonly used Wechsler Block Design test were dramatically reduced. Similarly, an 11-year follow-up of elderly subjects analyzed both speed and quality of performance (errors) on a parallelogram test. As expected, speed declined with age, but the quality of the performance actually improved significantly. This body of literature suggests that declining speed contributes to some of the findings that report visuospatial processing deficits in normal aging.

Speed does not appear to account for all of the visuospatial changes observed in healthy aging, however. Mental rotations of objects or spatial coordinates, accurate copy of complex geometric designs, and mental assembly of objects typically worsen with age even when unlimited time is allowed to perform such tasks. Furthermore, when speed is included in scoring, some studies have reported disproportionate slowing on visuospatial tasks compared to verbal tasks. Overall, some studies may exaggerate the visuospatial decline observed in normal aging because of the role speed plays in many tasks used to assess visuospatial function. However, abstract spatial abilities may decline with age, even when speed is controlled.

Psychomotor Functions

An age-associated increase in reaction time, related to both a general reduction in the speed of cognitive processing and to changes in peripheral motor skills, has been consistently reported. Age-related declines in brain dopamine activity and periventricular white matter changes may be associated with reduced cognitive speed and basic motor functions. As a result, performance on tests requiring speed and quick reaction to stimuli is likely to decline. As previously noted, increased psychomotor speed and reaction time are believed to underlie many of the age-related changes noted on neurocognitive testing, particularly tasks involving perceptual speed, attention, and working memory. In addition, changes in psychomotor functions can be associated with changes in real world tasks, such as driving. As a result, it is important to monitor the manner in which physical changes are impacting an individual’s level of safety in performing daily activities.

In the following section we review cognitive symptoms associated with common diseases affecting older adults. A summary of these symptoms is presented in Table 62-2.

Cardiovascular Disease

In addition to increasing the risk for developing stroke and/or vascular dementia, cardiovascular disease potentially jeopardizes cognitive function via multiple mechanisms.

Cognitive impairment subsequent to coronary artery bypass graft (CABG) surgery has been reported in up to 80% of patients, and older age significantly increases the risk for development of such complications. A wide range of cognitive deficits, including problems with attention and concentration, processing speed, memory, and visuospatial function, has been noted in patients immediately following surgery. Initial reports suggested that postoperative cognitive function stabilizes or even improves after a period of approximately 12 months in those patients who demonstrate initial decline. However, recent longitudinal data provide evidence that such patients are at high risk for continued cognitive deterioration 5 years postsurgery. For example, one study found that 42% of patients showed a significant decline in one or more areas of cognitive function 5 years postsurgery, including verbal and visual memory, attention and concentration, and general cognition. Notably, post-CABG neurocognitive status is related to overall quality of life, and current recommendations underscore the importance of closely monitoring cognitive status in the years following cardiac surgery.

Hypertension

Essential hypertension has been associated with cognitive impairment independent of secondary disease or organ damage, particularly in older patients. Potential cognitive effects of primary hypertension include reductions in mental status, slowed reaction time, reduced attention and vigilance, weakened executive function, poor verbal fluency, and impaired visual organization and construction. Memory functions, including spatial recall, verbal recall, and word recognition, may also be affected in some hypertensive patients. In addition, secondary effects of hypertension may lead to an increased risk for cognitive decline in older age. For example, uncontrolled hypertension potentiates the development of subcortical white matter lesions, and adversely impacts cerebral blood flow and energy substrate delivery. While there is currently debate concerning the extent to which hypertension and related subcortical effects overtly impact cognition, recent findings suggest that hypertension is a significant risk factor for dementia, and treating hypertension reduces this risk. In particular, mid-life hypertension increases the risk of later-life cognitive impairment. Interestingly, blood pressure often declines in the period immediately preceding the onset of Alzheimer’s disease, and it has been suggested that low blood pressure in persons of advanced age may compromise brain function as a result of hypoperfusion. In particular, aggressive sudden lowering of blood pressure in older adults with long-term hypertension may potentially interact with their chronically upregulated cerebral vascular resistance and induce cerebral hypoperfusion. Thus, careful monitoring of blood pressure and gradual titration of medication regimens is of particular importance. Additional interest has been focused on the question of whether different methods of treating hypertension may confer particular protective effects on cognition. A recent epidemiologic study observed a reduced risk of dementia associated with the use of potassium-sparing diuretics. However, no adequately controlled, randomized trials have been conducted to definitively answer this question.

Nutritional Deficiency

Older adults are at considerable risk for nutritional deficiencies as a consequence of poor diet and malabsorption syndromes. Much research in this area has focused on deficiencies of B vitamins. A recent meta-analysis concluded that reduced folate levels may be associated with lowered cognitive function and increased risk of Alzheimer’s disease; however, the accumulated evidence did not support a similar relationship for B-12 and B-6. Some studies have suggested that supplementation may improve cognitive performance in deficient individuals.

B vitamins play an important role in homocysteine metabolism. Homocysteine is an independent risk factor for cerebrovascular and cardiovascular disease. In patients with both Alzheimer’s disease and vascular dementia, elevated plasma homocysteine levels have been reported, and recent studies suggest that homocysteine levels are related to cognitive function in normal aging. Reduced performance on tests of mental status, nonverbal pattern abstraction, construction, and processing speed are reported in patients with high plasma homocysteine. Given that plasma homocysteine and folate levels are inversely related, it is conceivable that such cognitive deficits are related to reduced folate rather than to increased homocysteine per se. Recent data suggest, however, that homocysteine increases the risk for cognitive decline independent of both folate levels and other vascular risk factors.

Type 2 Diabetes Mellitus

Much attention has been given to the rampant epidemic of type 2 diabetes mellitus (T2DM) in older adults, a trend thought to be largely attributable to obesity and physical inactivity. Current prevalence estimates suggest that 20% of adults older than 65 years are afflicted with T2DM. The negative impact of T2DM on multiple medical systems is well known. The clear impact of T2DM on cognitive function in older adults is less-widely known, but accruing evidence demonstrates that these patients show pronounced impairment in attention and verbal memory when compared to healthy age-matched adults, and show accelerated cognitive decline over time. Complex attentional impairment is most common, involving the inability to handle multiple streams of information or attend to information in the face of competing stimuli. Verbal memory deficits typically affect the ability to encode new verbal information. The magnitude of such impairment may vary from subtle subjective complaints to pronounced impairment that interferes with daily activities and may interfere with the patient’s ability to adhere to complex treatment regimens. The mechanisms causing attentional and memory impairments are likely multifactorial and include vascular factors, as described above, in addition to the potential negative effects of hyperglycemia and glucose toxicity thought to cause oxidative injury. Recent work also suggest that insulin resistance, independent of hyperglycemia, may have negative consequences on brain systems mediating memory and attention. This intriguing possibility has implications for therapeutic approaches to treating T2DM, suggesting that strategies focused on improving insulin sensitivity may be preferable to those focused on augmenting insulin levels. Successful treatment of T2DM has been shown to improve cognitive function. The importance of treating and preferably preventing T2DM has been underscored by recent findings that it is a risk factor for various forms of neurodegenerative disease, including Alzheimer’s disease, vascular dementia, and Parkinson disease.

Oxygen Deprivation

Chronic Obstructive Pulmonary Disease

Emphysema and chronic bronchitis obstruct airflow, resulting in hypoxemia and hypercapnia. Cognitive dysfunction is commonly observed in chronic obstructive pulmonary disease, although the specific skills affected appear to be broad and diffuse. Deficits in verbal and visual memory, attention, abstraction, psychomotor speed, information processing speed, and IQ have all been reported. These changes in cognition appear to be caused by hypoxemia. The decrease in arterial oxygen partial pressure correlates with neuropsychological impairments, and most studies indicate that oxygen therapy results in modest improvements in cognition. Depression is also common in chronic obstructive pulmonary disease and must be considered as another cognitive risk factor.

Obstructive Sleep Apnea