The Handbook of Alzheimer's Disease and Other Dementias

Andrew E. Budson, Neil W. Kowall, Andrew E. Budson, Neil W. Kowall

• Publisher: Wiley-Blackwell
• Year: 2011
• Print ISBN:
  9781118672853
  9781405168281
• Edition: 1
• eBook ISBN:
  9781444344097
• Topic: Psychology
• Subtopic: Developmental Psychology
• Index: Psychology

The reference is a broad-ranging review of Alzheimer's disease and other dementias from both basic and clinical neuroscience perspectives; it provides scientists and medical professionals with an extensive introduction and an up-to-date review of cutting-edge scientific advances.

• Brings the reader up-to-date with cutting-edge developments in this exciting and fast-paced field
• Summarizes the most recent developments in the fields of Alzheimer's disease and dementia
• Brings together articles from a prominent and international group of contributors
• Encompasses a unique range of topics, combining basic molecular perspectives and cognitive neurosciences

Part I: Common Dementias

1

Alzheimer’s Disease

Alan M. Mandell and Robert C. Green

History

In 1871, over 30 years before Alois Alzheimer published his seminal cases, James Crichton-Browne may have been among the first physicians to remark upon the relationship between “brain wasting” and “premature dotage” in a letter to Charles Darwin (Snyder & Pearn, 2007). Age-related mental deterioration as an entity had been recognized virtually for recorded history (Boller et al., 2007; Mandell & Albert, 1990). Emil Kraepelin, however, was one of the few 19th-century giants of medicine who recognized the connection between brain pathology and mental dissolution in the elderly (Stam, 1985). He referred to “Morbus Alzheimer” as early as 1908 and used the eponym in the 1910 edition of his textbook (Kraepelin, 1910). Over the next century plus, Alzheimer’s disease (AD) has become the focus of one of the most intensive investigations in medical history. A Google search for AD now generates over 18 million hits.

Alzheimer examined 51-year-old Auguste D. in 1901 (Graeber, 2006). Her husband had noted a relatively sudden change in her behavior, dominated by panic, terror and suspicions of his having an affair with a neighbor. She neglected her housework, hid objects and fumbled in the kitchen. Over the next several months, she became increasingly restless and a disturbance to their neighbors. By the time of her admission to hospital, which she never left, she suffered from “weakening of memory, persecution mania, sleeplessness, restlessness,” had an “amnestic writing disorder,” was unable to perform any mental or physical work and was “rarely free from fear and agitation.” Periods of calm cooperation alternated with physical aggression towards other patients, “groping their faces as if she were blind” (Page & Fletcher, 2006).

Alzheimer was met with silence when he first presented his case (Alzheimer, 1906) of “a distinct disease process” (Nair & Green, 2006). Following his initial publication of 1907 (Alzheimer, 1907), he issued his classic review article in 1911 (Alzheimer, 1911).

With a few exceptions and for several reasons (Nair & Green, 2006), “Alzheimer’s disease” for roughly the next 50 years denoted “presenile” dementia and differed from the “normal” senility associated with old age, despite Alzheimer’s assertion that there were no significant pathological differences between older and younger cases (Spielmeyer, 1916). Kraepelin as well opined that this illness is “a peculiar disease process that is largely independent of age” (Kraepelin, 1910).

Alzheimer described the now familiar distinctive pathology in his original 1907 article. Slides from two patients were rediscovered in 1992 and 1997, and those from Auguste D. clearly demonstrate numerous characteristic cortical plaques and tangles (Graeber, 2006).

Epidemiology of Dementia and AD

In virtually all developed countries, the oldest segments of society are increasing at the fastest rate and an epidemic of age-related diseases is already upon us. The dementia syndrome is largely a provenance of the elderly and is a major part of a looming public health crisis. The global prevalence of dementia of any cause in 2005 was about 24 million with yearly incidence of almost 5 million, tantamount to adding a new case every 7 seconds (Ferri et al., 2005).

AD accounts for about 55–70% of adult-onset dementia in the industrialized world (Lim et al., 1999), is the fifth leading cause of death in Americans older than 65, and, in contrast to the decreasing death toll attributable to other major diseases, that due to AD is on the rise (Mebane-Sims & Alzheimer’s Association, 2009) (Figure 1.1).

Figure 1.1 Population-based vs. clinic-based estimates of dementia

Source: Modified from Green, R.C. (2005). Diagnosis and Management of Alzheimer’s Disease and Other Dementias (2nd edn.). Caddo, OK: Professional Communications, Inc., by permission

AD incidence is age related and doubles about every 5 years from age 65 through the 90s (Bachman et al., 1993; Berlau, 2007). The exact prevalence of AD is difficult to determine because, among other reasons, death certificates of people with end-stage AD often list infection or “cardiopulmonary arrest” as the proximate cause. Currently, over 5 million Americans have AD with incidence of a new case about every 70 seconds. In the United States, there will be at least 8.5 million people with AD by the year 2030, about 13 to 25 million in 2050 (a new case every 33 seconds) (Hebert et al., 2003; Mebane-Sims & Alzheimer’s Association, 2009) plus an unknown number with other dementias. National direct and indirect monetary costs of caring for people with Alzheimer’s disease alone is already at least $100 billion annually in the United States (Koppel, 2003), where nursing home cost per patient currently hovers around $50,000 per year, and over $300 billion per annum globally (Dartigues, 2009). We therefore need hardly emphasize the current and growing economic impact of AD, the “coming plague of the 21st century,” on health systems worldwide. More specific epidemiological data are discussed in this and other chapters.

Dementia

Definition, Evaluation, Management, and Treatment

Symptoms common to most dementias include forgetfulness, language deterioration, mood changes, impaired judgment, and loss of initiative. There is nevertheless no universally accepted definition of “dementia,” which has been broadly characterized as a syndrome, as shorthand for unsuccessful aging, and as a specific diagnosis (Green, 2005), that is, as a synonym for AD. Within its multitude of definitions, diagnostic criteria have routinely included memory impairment, decline in social or occupational function (American Psychiatric Association, 2000), progressive deterioration, incurability, and irreversibility. Clinicians must nevertheless be aware that pathological processes underlying many causes of dementia are static and that a few are treatable. Furthermore, while the association between dementia and memory disorder is almost ubiquitous, significant amnesia is not a salient feature of every dementing disease. Evidence of functional decline, e.g., in personal hygiene, bill paying, housecleaning, personality, etc., is, at least for research purposes, currently the clinical marker separating “possible dementia” and “normal aging” from “dementia.” Many factors can nevertheless mask or delay occupational or social incompetence and we favor a somewhat broader definition.

“Dementia,” as used in this chapter, is a syndrome of acquired persistent intellectual impairments characterized by deterioration in at least three of the following domains: memory, language, visuospatial skills, personality or behavior, and manipulation of acquired knowledge (including executive function) (Cummings, 2004; Cummings & Benson, 1992; Cummings & Mega, 2003). According to this definition, mental retardation and acute confusional states (ACS; delirium) do not qualify, the former because it is not acquired, the latter because multiple cognitive impairments associated with it by definition are temporary (see subsequent discussion of the ACS). The presence of a dementia is supported by a combination of a carefully obtained history, physical and mental status examinations, significant impairment on neuropsychological tests corrected for age and education, and a change in test scores over a 6–12-month interval (Mesulam, 2000).

This definition, like all the others, is not perfect. Persons with superior pre-morbid intellect and greater cognitive reserve (Roe et al., 2007) may suffer decline in occupational performance which nevertheless escapes even the most detailed clinical assessment and which results in no other objective functional impairment (Cummings, 2005a; Strub & Black, 2000). Some ultimately dementing disorders (Benson et al., 1988; Dubois et al., 2007; Mesulam, 2003) may manifest for years as gradual deterioration limited to a single cognitive domain which in turn can influence execution and interpretation of other cognitive functions (Mesulam, 2000).

“Dementia of the Alzheimer type” (DAT) refers to the clinical syndrome which by far is that most commonly associated with autopsy-proven (pathologic) AD.

Recognition and Differential Diagnosis of the Dementia Syndrome

Management and treatment of dementia begins with its recognition, which is reasonably straightforward either when the patient or an independent historian expressly raises cognitive (or behavioral) deterioration as an issue, or it becomes obvious in context with other medical issues (e.g., following hospital admission). Recognition is a not inconsiderable concern, however, because cognition and behavior are indeed not issues for many “community dwelling elderly” who are nevertheless already demented and just one fall, infection, change of address or assault of a spouse away from health system entry for these issues (Albert et al., 1991).

Recognition is further hindered because widespread neuropsychological testing, imaging and laboratory screening for asymptomatic elderly people is not economically feasible. Furthermore, many health professionals as well as lay people persist in believing that cognitive loss is an inevitable and “natural” consequence of aging rather than a reflection of brain damage. Although there is some longitudinal evidence that general cognition “normally” recedes in a person’s mid-70s (Brayne et al., 1999), much of the decline previously attributed to age alone probably reflects the effect of mild unrecognized dementia. Studies of optimally healthy older adults who are evaluated each year suggest that overall cognitive function may slow somewhat but does not reflect a significant longitudinal decline for these persons (Schaie, 1989). Therefore, in the absence of disease, older adults can reasonably expect stable overall cognitive function and little or no interference with performance of everyday activity (Rowe & Kahn, 1987). This requires a fundamental shift in the approach to the aging patient, in that clinicians should not automatically attribute memory or cognitive problems that interfere with everyday activities to normal aging, and this should be communicated to the patient’s family.

Among adults over 85 years of age, the definition of “normal” cognition is much more difficult to establish. Many neuropsychological tests have not been validated for this group of the “oldest old,” and vision and hearing problems often interfere with assessment. Apparently unimpaired individuals over 85 are nonetheless at high risk of cognitive decline (Crystal et al., 2000; Howieson et al., 2003).

Most clinicians do not routinely test mental status in older individuals unless they receive complaints either from the patient or the patient’s family. Many demented patients do not, however, so-complain and, on average, most family members do not seek medical attention for the patient until several years after onset of symptoms (if the dementia is progressive). Most patients with DAT, therefore, escape early diagnosis, particularly in primary care settings (Callahan et al., 1995; Cummings, 2004; Cummings & Mega, 2003; Dartigues, 2009; Petrovitch et al., 2001). Cognitive symptoms that are not associated with obvious functional impairment may be dismissed or minimized.

The prevalence of truly curable dementia in the community has been debated (Clarfield, 1995; Weytingh et al., 1995). The probability of finding a reversible cause for dementia has nevertheless likely declined greatly in the past 20 years (Clarfield, 2003; Mok et al., 2004). Prompt recognition of dementia remains important all the same because emerging diagnostic techniques and increasingly effective therapeutic interventions are altering the definition of “treatable” (Fagan et al., 2007). Advantages of an early-as-possible diagnosis of dementia are listed in Table 1.1.

Table 1.1 Advantages of early diagnosis in dementing conditions

Source: Green, R. C. (2005). Diagnosis and management of Alzheimer’s disease and other dementias (2nd edn.). Caddo, OK: Professional Communications. Professional Communications, Inc, by permission

For every case Provide a diagnostic answer and education for the patient and/or family

For patients with reversible or static diseases (e.g., depression, stroke) Relieve the fear of an irreversible or progressive disease Treat the underlying disease Initiate prevention and/or rehabilitation strategies

For patients with irreversible and progressive diseases (e.g., Alzheimer’s...

Table of contents

• Cover
• Series page
• Title page
• Copyright page
• Dedication
• Contributors
• Foreword
• Preface
• Part I: Common Dementias
• Part II: Pathogenesis and Disease Mechanisms
• Part III: Cognitive and Behavioral Dysfunction
• Part IV: Neuroimaging in Dementia
• Index
• Color plates
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