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Clinical Stages of Alzheimer's Disease
Alzheimer's disease (AD) is a characteristic process with readily identifiable clinical stages. These clinical stages exist in a continuum with normal aging processes. The clinical stages of AD can be described in alternative ways. For example, they can be described globally or they can be described in terms of constituent elements, referred to as clinical axes. One of these clinical axes, functioning and self-care, is particularly useful in describing the progression of AD. However, many conditions, particularly in aged persons, can interfere with functioning apart from AD. For these and other reasons, functioning changes alone do not adequately describe the progress of AD. However, the combination of global changes and their functional concomitants can provide a clear map or the progress of AD. This clinical map is enriched by noting the common behavioral concomitants of the stages. However, the behavioral and mood manifestations of AD are much more diverse than the cognitive and functional features of the disease progression.
Globally, seven major stages from normality to most severe AD are identifiable. Functionally, 16 stages and substages corresponding to the global stages are recognizable. These global and functional clinical stages and substages of aging and AD are summarized as follows.
Stage 1: Normal
At any age, persons may potentially be free of objective or subjective symptoms of cognition and functional decline and also free of associated behavioral and mood changes. We call these mentally healthy persons at any age, stage 1, or normal (Figure 1).
Figure 1 Stage 1, Normal
Stage 2: Normal aged forgetfulness
Half or more of the population of persons over the age of 65 experience subjective complaints of cognitive and/or functional difficulties. The nature of these subjective complaints is characteristic. Elderly persons with these symptoms believe they can no longer recall names as well as they could 5 or 10 years previously. They also frequently develop the conviction that they can no longer recall where they have placed things as well as previously (Figure 2). Subjectively experienced difficulties in concentration and in finding the correct word when speaking, are also common.
Figure 2 Stage 2: Normal aged subjective forgetfulness.
Why can't I remember where I put those papers?
I used to remember where everything that I put away was located.
Various terms have been suggested for this condition, but normal aged forgetfulness is probably the most satisfactory terminology. These symptoms, which by definition, are not notable to intimates or other external observers of the person with normal aged forgetfulness, are generally benign. However, there is some recent evidence that persons with these symptoms do decline at greater rates than similarly aged persons and similarly healthy persons who are free of subjective complaints.
Stage 3: Mild cognitive impairment
Persons at this stage manifest deficits which are subtle, but which are noted by persons who are closely associated with the stage 3 subject. The subtle deficits may become manifest in diverse ways. For example, the person with mild cognitive impairment (MCl) may noticeably repeat queries. The capacity to perform executive functions also becomes compromised. Commonly, for persons who are still working, job performance may decline. For those who must master new job skills, decrements in these capacities may become evident. For example, the MCIsubject may be unable to master new computer skills (Figure 3). MCI subjects who are not employed, but who plan complex social events, such as dinner parties, may manifest declines in their ability to organize such events. Other MCI subjects may manifest concentration deficits. Many persons with these symptoms begin to experience anxiety, which may be overtly evident.
Figure 3 Stage 3: Mild memory impairment.
In his stage, ability to perform complex occupational and social tasks is compromised and may be noticeable by colleagues. This is a 'border stage' which does not necessarily progress. When progression does occur, the true (potential) duration of this stage is probably 7 years; however, symptoms are commonly not observed until this stage has progressed at least midway through its temporal course.
The prognosis for persons with these subtle symptoms of impairment is variable, even when a select subject group who are free of overt medical or psychological conditions which might account for, or contribute to, the impairments are studied. A substantial proportion of these persons will not decline, even when followed over the course of many years. However, in a majority of persons with stage 3 symptoms, overt decline will occur, and clear symptoms of dementia will become manifest over intervals of approximately 2 to 4 years. In persons who are not called upon to perform complex occupational and/or social tasks, symptoms in this stage may not become evident to family members or friends of the MCI patient. Even when symptoms do become noticeable, MCI subjects are commonly midway or near the end of this stage before concerns result in clinical consultation. Consequently, although progression to the next stage in MCI subjects commonly occurs in 2 to 3 years, the true duration of this stage, when it is a harbinger of subsequently manifest dementia, is probably approximately 7 years.
Management of persons in this stage includes counseling regarding the desirability of continuing in a complex and demanding occupational role. Sometimes, a 'strategic withdrawal’ in the form of retirement, may alleviate psychological stress and reduce both subjective and overtly manifest anxiety.
Stage 4: Mild Alzheimer's disease
Symptoms of impairment become evident in this stage. For example, seemingly major recent events, such as a recent holiday or a recent visit to a relative, may, or may not, be recalled. Similarly, overt mistakes in recalling the day of the week, month or season of the year may occur. Patients at this stage can still generally recall their correct current address. They can also generally correctly recall the weather conditions outside and very important current events, such as the name of a prominent head of state. Despite the overt deficits in cognition, persons at this stage can still potentially survive independently in community settings. However, functional capacities become compromised in the performance of instrumental (i.e. complex) activities of daily life. For example, there is a decreased capacity to manage personal finances. For the stage 4 patient who is living independently, this may become evident in the form of difficulties in paying rent and other bills. A spouse may note difficulties in writing the correct date and the correct amount in paying checks (Figure 4). The ability to independently market for food and groceries also becomes compromised in this stage. Persons who previously prepared meals for family members and/or guests begin to manifest decreased performance in these skills. Similarly, the ability to order food from a menu in a restaurant setting begins to be compromised. Frequently, this is manifest in the patient handing the menu to the spouse and saying 'you order'.
Figure 4 Stage 4: Mild Alzheimer's disease.
The diagnosis of Alzheimer's disease can be made with considerable accuracy in this stage. The most common functioning deficit in these patients is a decreased ability to manage instrumental (complex) activities of daily life. Examples of common deficits include decreased ability to manage finances, to prepare meals for guests, and to market for oneself and one's family. The stage 4 patient shown has difficulty writing the correct date and the correct amount on the check. Consequently, her husband has to supervise this activity. The mean duration of this stage is 2 years.
The dominant mood at this stage is frequently what psychiatrists term a flattening of affect and withdrawal. In other words, the patient often seems less emotionally responsive than previously. This absence of emotional responsivity is probably intimately related to the patient's denial of their deficit, which is often also notable at this stage. Although the patient is aware of their deficits, this awareness of decreased intellectual capacity is too painful for most persons and, hence, the psychological defense mechanism known as denial, whereby the patient seeks to hide their deficit, even from themselves where possible, becomes operative. In this context, the flattening of affect occurs because the patient is fearful of revealing their deficits. Consequently, the patient withdraws from participation in activities such as conversations.
In the absence of complicating medical pathology, the diagnosis of AD can be made with considerable certainty from the beginning of this stage, Studies indicate that the duration of this stage of mild AD is a mean of approximately 2 years.
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