Normal Aging & Dementia
- Jun 02, 2011
- Normal Aging & Dementia
- Concepts and Criteria
- Normal Aging
- Age-associated Memory Impairment
- Age-associated Cognitive Decline
- Mild Cognitive Impairment
- Diagnose dementia
- Cognition and Cognitive Testing
- Memory Impairment
- Executive Ability
- Visuospatial/Constructional and Visuoperceptual Abilities
- Structural Imaging
- Entorhinal Cortex
- Other Structural Changes
- Functional Imaging
- Functional Activation Studies
- Clinical Conclusions
Recent research has advanced our understanding of the boundary between normal aging and dementia. In addition to illuminating changes associated with both normal and abnormal aging, researchers have identified a group of individuals whose cognitive deficits place them in an intermediate position on the continuum between normal aging and dementia. The study of the continuum is complicated by remarkable variability across individuals and domains of functioning.
Aging is characterized by both decremental and incremental changes (Albert 1988). As a result, the range and standard deviation for almost any variable of interest increase with age (Rowe and Wang 1988). Emerging evidence from studies of neurogenesis indicates regenerative potential in the adult human brain (Kempermann and Gage 1999; Horner and Gage 2000; Shihabuddin et al. 2000) and possible neural recruitment (Reuter-Lorenz, Stanczak, and Miller 1999) that may be associated with successful cognitive aging or recovery from brain insults.
Concepts and Criteria
Normal and Successful Aging
Normal aging has been conceptualized as the typical changes in behavior that occur with age (Schroots and Birren 1993). The common conception has been that subtle declines in cognition occur as part of the normal aging process.
However, studies have included individuals with other age-associated conditions, such as cardiovascular disease or diabetes, which can affect cognition.
In normal aging, you can expect a number of skills and abilities to be intact or only slightly different. You will continue to be independent in what are considered daily activities, such as bathing, dressing, driving, and working. You may notice memory loss, but you will be able to give details about those incidents of forgetfulness; and you will be more concerned about this type of memory loss than your close family members. Despite these occasional lapses of forgetfulness, your memory for recent events and conversations will not be a problem. You may notice occasional difficulty with finding the right word that you want to use, but your vocabulary will remain rich. Also, a part of the aging process will be the annoying problem of getting lost in a familiar place. You may have to give yourself a few moments to remember your way (but you WILL remember). As you age, you may still be able to operate your common household appliances, even if you may be unwilling to learn how to use new devices.
During the process of normal or "healthy" aging, there are natural changes that take place if one is free of any disease. Dr. Adam Gazzaley, MD of the University of California Memory and Aging Center has stated that some changes in the ability to think are considered a normal part of the aging process. Dementia, on the other hand, is not a normal outcome of aging. Being able to recognize the difference between normal aging and dementia in you or a loved one can assist you in determining when additional help or evaluation is needed. When the time comes for the help you need, turn to the retirement and assisted living communities of Retirement Unlimited, Inc for the right care at the right time.
More recently, some researchers examined normal elderly individuals without age-associated medical conditions, and evidence is emerging that their cognition can remain relatively stable, at least until about 85 years of age (e.g., Emery 1985; Schaie and Willis 1991; Hickman et al. 2000; Snowdon 2001). The critical question is whether systematic or regular changes occur with age in the absence of and independent of disease. Addressing this question, a classical investigation by Birren and colleagues, which has been reliably replicated, found that even optimally healthy individuals between ages 65 and 91 showed significantly slower psychomotor speed than did young adults; this age-related psychomotor slowing in the absence of any disease was found to have a negative impact on cognitive measures that required fast response (Birren, Woods, and Williams 1980; Salthouse 1985; Spirduso and MacRae 1990; Schaie and Willis 1991).
Concomitantly, these optimally healthy disease-free elderly individuals evidenced slowing of electrical activity of the brain, or EEG changes, as a function of normal aging (Birren 1965; Birren, Woods, and Williams 1980; Schaie and Willis 1991). Shedding additional light on this issue, recent studies provide new insights on the aging brain, with evidence that neural regeneration and functional brain reorganization may help to preserve cognition during the aging process (Kempermann and Gage 1999; Reuter-Lorenz, Stanczak, and Miller 1999; Shihabuddin et al. 2000). Psychosocial factors that may contribute to successful cognitive aging include diet, exercise, no substance abuse (e.g., alcohol, illegal drugs, prescription drugs), social involvement, and very importantly, mental activity and new learning (e.g., Baltes and Baltes 1990; Baltes 1993; Nicolas et al. 2001).
Age-associated Memory Impairment
Initially used to refer to the "benign forgetfulness" (Kral 1958, 1962) frequently reported as healthy individuals grow older, the term age-associated memory impairment (AAMI) was introduced in 1986 by a National Institute of Mental Health work group (Crook et al. 1986). While the original concept of benign forgetfulness was defined without formal psychometric testing and criteria, it assumed that some gradual cognitive change with aging is normal. The formal criteria developed by the 1986 work group included: (1) age 50 or older; (2) subjective decline or loss in memory function; (3) performance at least one standard deviation (SD) below the mean of young adults on memory tests; (4) preserved intellectual ability; (5) failure to meet the criteria for depression; and (6) failure to meet the criteria for dementia. Using these criteria, however, at least one study (Smith et al. 1991) showed that a very large percentage of the older population would be classified as having AAMI.
Age-associated Cognitive Decline
The term age-associated cognitive decline (AACD) has been used to describe a group of older individuals in which multiple domains of cognition may be mildly compromised relative to younger individuals (Levy 1994). As is the case for AAMI, the use of young adults as the reference group for AACD means that many older adults will be classified as having AACD, yielding little discriminative or predictive value to the classification (Shah, Tangalos, and Petersen 2000).
Mild Cognitive Impairment
The term mild cognitive impairment (MCI) has been used to describe the group of older individuals who have greater than expected memory impairment for their age, but do not meet the criteria for dementia (Petersen 2000). Unlike AAMI and AACD, the reference group for a diagnosis of MCI is composed of age-matched peers. Mild cognitive impairment generally presents with subjective memory difficulties of insidious onset. In fact, subjective cognitive complaints can be a harbinger of dementia even before the development of demonstrable cognitive deficits, particularly in highly educated individuals (Jonker, Geerlings, and Schmand 2000). When these complaints are corroborated by an informant, they are more likely to be borne out on further clinical evaluation. As time progresses, the forgetfulness becomes more frequent and significant. In spite of these developing memory problems, social and occupational functioning are relatively preserved. Nonmemory cognitive domains are relatively spared in MCI, as originally defined, but in practice may fall slightly below age- and education-based normative data. For example, speed of processing and cognitive flexibility may be subtly impaired (Petersen 2000).
The formal criteria for mild cognitive impairment include: (1) significant memory complaints, such as a chronic forgetting of important information, preferably corroborated by an informant; (2) memory impairment on standardized tests relative to age- and education-matched healthy controls (at least 1.5 SD below the mean); (3) otherwise normal cognitive function; (4) normal activities of daily living; and (5) failure to meet the criteria for dementia (Flicker, Ferris, and Reisberg 1991; Petersen et al. 1999).
Unlike the concept of age-associated memory impairment, the underlying assumption of the construct of mild cognitive impairment is that the memory impairment is not normal and that there is an increased likelihood of progression to dementia, particularly dementia of the Alzheimer type (DAT). Current estimates indicate conversion rates from MCI to DAT of between 6% and 25% per year (Petersen et al. 2001), with most studies falling in the range of 10-15% per year (Flicker, Ferris, and Reisberg 1991; Tierney et al. 1996; Bowen et al. 1997; Devanand et al. 1997; Petersen et al. 1999, 2001). This contrasts with the 1-2% per year rate at which DAT develops in the normal elderly population.
Petersen and colleagues (1999) reported that up to 40% of individuals diagnosed with MCI convert to DAT within four years, and Morris et al. reported a conversion rate of more than 80% in individuals followed for 9.5 years.
Given the high likelihood of progression to dementia of the Alzheimer type in individuals with mild cognitive impairment, early identification and diagnosis may be important (Almkvist and Winblad 1999). While it is not yet clear who will or will not convert to DAT, several potential risk factors have been identified. Prominent among them is the presence of the apolipoprotein E (ApoE)-4 allele. ApoE is a marker initially studied as a risk factor for cardiovascular disease. It is involved in the normal regulation of phospholipid metabolism and cholesterol and may play a role in neural repair. Identified cognitive predictors include subtle decreases on verbal memory tested over time in longitudinal studies (Collie et al. 2001) and failure to benefit from cueing at recall (Petersen et al. 1994). Neuroimaging predictors include mesial temporal lobe changes, such as decreased volume of the hippocampus (Jack et al. 1999) and entorhinal cortex (Fox et al. 1996; Juottonen et al. 1998, 1999; Jack et al. 1999; Killiany et al. 2000). Magnetic resonance imaging or other techniques such as functional neuroimaging may be useful to distinguish those persons with MCI who will develop DAT from those who will not (Celsis 2000). The trajectory of decline in memory and medial temporal lobe volume is likely to be predictive of conversion to DAT (e.g., Chen et al. 2001).
As more researchers have become involved in studying mild cognitive impairment, it has become clear that it is not a homogeneous disorder (Ritchie, Artero, and Touchon 2001). For example, Petersen et al. (1999) distinguished between two types of MCI. They used the term amnestic MCI to describe the variant that progresses to DAT, and differentiated this from nonamnestic MCI.
We will limit our discussion to the more widely recognized amnestic variant of MCI, which has been most addressed in the available literature. Future research on nonamnestic MCI will be important; this entity may progress to Pick, Lewy body, frontotemporal, or other types of dementia.
Laura A. Flashman, Ph.D.,
Heather A. Wishart, Ph.D.,
Thomas E. Oxman, M.D.,
and Andrew J. Saykin, Psy.D.
- Kral, V.A. 1958. Neuro-psychiatric observations in an old peoples home. Journal of Gerontology 13:169-76.
- Kral, V.A. 1962. Senescent forgetfulness: Benign and malignant. Canadian Medical Association Journal 86:257-60.
- Krasuski, J.S., G.E. Alexander, B. Horwitz, et al. 1998. Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls). Biological Psychiatry 43 (1):60-68.
- Kuhl, D.E., R.A. Koeppe, S. Minoshima, et al. 1999. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology 52:691-99.
- Laakso, M.P., H. Soininen, K. Partanen, et al. 1995. Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer's disease: correlation with memory functions. Journal of Neural Transmission, Parkinson Disease and Dementia Section 9 (1):73-86.
- Lange, K.W., B.J. Sahakian, N.P. Quinn, et al. 1995. Comparison of executive and visuospatial memory function in Huntington's disease and dementia of Alzheimer type matched for degree of dementia. Journal of Neurology, Neurosurgery, and Psychiatry 58 (5):598-606.
- Lauter, H. 1985. What do we know about Alzheimer's disease today? Danish Medical Bulletin 32 (Suppl. 1):S1-21.
Full References »
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