Archives of Gerontology and Geriatrics
Volume 36, Issue 1 , Pages 57-65, January 2003

Normal aging and AIDS

  • J.L Sánchez Rodrı́guez

      Affiliations

    • Department of Basic Psychology, Psychobiology and Methodology, Faculty of Psychology, University of Salamanca, Avenida de la Merced, 109-131, 37005 Salamanca, Spain
    • Corresponding Author InformationCorresponding author. Tel.: +34-923-294400x3285; fax: +34-923-294608
    • ,
  • M Rodrı́guez Álvarez

      Affiliations

    • Department of Clinical Psychology and Psychobiology, Faculty of Psychology, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain

Received 4 February 2002; received in revised form 15 July 2002; accepted 19 July 2002.

Article Outline

Abstract 

Normal aging is accompanied by a wide range of changes in brain structure and function. In this work we seek to examine the hypothesis that normal aging results in neuropsychological findings similar to those produced by neuropsychological impairment related to AIDS. Specifically, we attempt to compare the level of neuropsychological performance in three groups: a normal elderly group (n=46), a young group of AIDS patients (n=36), and a young group of normal subjects (n=22). The results indicated that, despite age differences between the normal elderly and AIDS patients, there was great similarity in the neuropsychological test performance of these two groups. In contrast, both groups demonstrated significantly different neuropsychological test performance than that evidenced by the younger normal controls. These results support the notion that neuropsychological changes related to normal aging are of a nature similar to those observed in AIDS and, therefore, affect functions subserved by frontal–subcortical brain regions.

Keywords:  AIDS, Normal aging, Neuropsychological performance, Frontal–subcortical dysfunction

 

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1. Introduction 

Normal aging is accompanied by a wide range of changes in brain structure and function. However, neuropsychological theories of aging are very limited, since most research into brain behavior has been addressed to pathological conditions such as Alzheimer's or Parkinson's disease. Decline is a part of normal cognitive aging. Areas that decline with age include fluid intellectual abilities, speed of performance, complex attentional processes, memory, visuospatial abilities, and some forms of abstract reasoning and problem solving (Albert, 1981, Colsher and Wallace, 1991, Johansson et al., 1992, Salthouse, 1992, Baddeley and Hitch, 1994, Godbout et al., 2000). These deteriorations emerge gradually, and are usually of minimal functional significance until very advanced old age. There are marked individual differences in rates of cognitive aging related to psychosocial parameters such as level of education or physical health (Akiyama et al., 1997).

Attempts have been made to correlate these changes in neuropsychological function with cerebral integrity in order to offer models explaining the neural basis of age related changes. Some have suggested that normal aging is associated with a mild form of dementia of the Alzheimer type (Berg, 1985), and others have emphasized the similarities between the neuropsychological alterations related to aging and those of patients with frontal–subcortical diseases (Whelihan and Lesher, 1985), suggesting that aging has its greatest effect on frontal–subcortical function (Moscovitch and Winocur, 1992, Fabiani and Friedman, 1997, Fabiani et al., 1998, Parkin and Java, 1999, Cahn-Weiner et al., 2000, Greenwood, 2000, West, 2000).

Since in AIDS patients, neuron loss, especially in the frontal cortex, cerebral atrophy, and demyelination of the white matter, mainly in the periventricular zones, corpus callosum, internal capsule, anterior commissure and optic tract have been described (Brew et al., 1988, Everall et al., 1991, Martin, 1994), it has been suggested that these findings represent the anatomical correlate of the neuropsychological deficits described in these subjects, which imply fronto–subcortical affection. Some authors (Van Gorp et al., 1989, Hinkin et al., 1990) have demonstrated that normal elderly and HIV encephalopathy patients evidenced a strong similarity in both level and pattern of neuropsychological performance despite their considerable age disparity, thus supporting the notion that normal aging differentially affects functions subserved by frontal–subcortical brain regions. Thus, Ludervold et al. (1994) studied four diagnostic groups categorized as ‘subcortical dementia’ (Huntington's disease, Parkinson's disease, multiple sclerosis and AIDS) and found that affected AIDS patients seemed to resemble patients with Huntington's disease more than the other diagnostic groups. Other authors (Morriss et al., 1992) found that multiple sclerosis patients showed more evidence of cognitive impairment than AIDS patients, however, both described current mental symptoms typical of a subcortical presentation.

Bearing in mind that the neuropsychological deficits described in HIV subjects suggest frontal/subcortical affection of the type observed in what are known as subcortical dementias, in this paper we present data to suggest that the neuropsychological changes associated with normal aging may be similar to those associated with AIDS and, therefore, related to frontal/subcortical dysfunction. The most appropriate model for testing the hypothesis empirically would compare a sample of normal elderly with a non-elderly sample with AIDS in order to remove the confound of advanced age.

In view of all the above, in this work we seek to examine the hypothesis that normal aging results in neuropsychological findings similar to those produced by neuropsychological impairment related to HIV. Specifically, we attempt to compare the level of neuropsychological performance in three Spanish groups: a normal elderly group, a young group of AIDS patients, and a young group of normal subjects. By comparing the neuropsychological test performance of normal elderly subjects with a younger group of AIDS patients, we can examine the degree to which the pattern of neuropsychological changes in normal aging is similar to that of a younger group with neuropsychological impairment related to HIV without neurological or medical pathologies that could affect the CNS, including HIV-associated dementia.

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2. Subjects and methods 

2.1. Subjects 

One hundred and four subjects representing three groups participated in the study. Forty-six consisted of neurologically intact normal elderly males, thirty-six were considerably younger males diagnosed with AIDS, and twenty-two were young neurologically intact normal controls. The normal elderly males were drawn from a larger group of normal elderly enrolled in a neuropsychological study of normal aging and dementia. No subject had a history of neurological disease, psychiatric illness, or history of substance abuse, mean age WQS 70.5±6.8 (S.D.), mean education=7.0±3.1 years (S.D.).

The 36 male AIDS patients met Center for Disease Control (CDC, 1992) criteria for AIDS and were selected from a larger cohort of HIV seropositive male drug users. All were outpatients at the time of testing and none presented, or had presented, neurological or medical pathologies that could affect the CNS, including HIV-associated dementia, psychiatric disturbances, and antisocial disturbance of the personality according to DSM-IV criteria (American Psychiatric Association, 1995). (Mean age=29.9±3.3; mean years of education=11.0±1.7).

None of the 22 normal younger males (Mean age=29.5±5.6; mean years of education=12.1±2.7) had a history of neurological, psychiatric or substance abuse disorder. Though significantly younger than the elderly group, their mean age [F(1,56)=0.157; P<0.05], and educational level [F(1, 56)=3.59; P<0.05] did not differ from the AIDS group.

2.2. Procedure 

All subjects were administered a battery of neuropsychological tests designed to assess a broad range of cognitive functions including attention/concentration, learning and verbal and visual memory, construction and visuospatial skills, language, speed of motor performance, cognitive flexibility and concept formation and reasoning (Table 1). All tests were administered in the standard fashion. The order of test administration was consistent for all groups and was made in the following way:

1.Spanish version of the Wechsler adult intelligence scale (WAIS) (Wechsler, 1995): similarities; digit span, digit symbol, block design and object assembly subtests.

2.Rey auditory verbal learning test (AVLT) (Rey, 1964).

3.Visual search and attention test (VSAT) (Trenerry et al., 1990).

4.Trail making test B (TMT) (Reitan, 1992).

5.Controlled oral word association (COWA) (Benton and Hamsher, 1978).

6.Benton visual retention test (BVRT) (Form C, Administration A) (Benton, 1981).

7.Boston naming test (Kaplan et al., 1986).

8.Stroop test (Golden, 1994).

9.Rey-Osterrieth complex figure (ROCF) (Rey, 1987).

10.Wisconsin card sorting test (WCST) (Heaton et al., 1993).

Table 1. Neuropsychological measures administered
Cognitive domainNeuropsychological test
Attention/concentrationWAIS: digit span subtest, visual search and attention test (VSAT), stroop test
Learning and memoryRey auditory verbal learning test (AVLT), Rey-Osterrieth complex figure (ROCF) (3 min delayed recall), Benton visual retention test (BVRT), (form C, administration A)
Construction and visuospatial functionRey-Osterrieth complex figure copy (ROCF), WAIS: block design and object assembly subtests
LanguageBoston naming test, controlled oral word association (COWA)
Speed of motor performance/cognitive flexibilityTrail making test B, WAIS: digit symbol subtest
Concept formation and reasoningWAIS: similarities subtest, wisconsin card sorting test (WCST)

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3. Results 

One-way analyses of variance (ANOVA) were performed for each neuropsychological measure to confirm whether there were significant differences between the three groups in each of the measurements of the neuropsychological battery. Table 2 shows the mean scores and standard deviations obtained for the three groups in each measurement, and gives the significant differences noted in the ‘post hoc’ multiple comparison tests.

Table 2. Group comparisons on neuropsychological measures (mean±S.D.)
Normal young mean age=29.5, n=22Normal elderly mean age=70.5, n=46AIDS mean age=29.9, n=36F
WAIS: similaritiesa, b, c19.18 (3.67)15.30 (5.18)11.69 (5.66)15.09
WAIS: digit spana, b14.45 (2.50)8.91 (1.82)9.94 (2.07)21.90
WAIS: digit symbola, b56.45 (12.49)36.48 (22.43)34.76 (13.30)11.81
WAIS: block designa, b41.45 (5.61)27.80 (7.35)26.92 (8.56)30.66
WAIS: object assemblya, b35.59 (5.39)26.76 (5.53)24.67 (9.94)16.10
AVLT, totala, b53.05 (8.77)39.89 (8.79)35.19 (9.45)27.40
VSATa, b133.18(21.58)81.15(41.70)96.50(37.21)14.92
Trails Ba, b64.59 (17.61)180.56 (95.46)143.86 (80.75)15.67
COWAa, b41.18 (7.91)28.63 (9.91)27.06 (9.47)17.59
BVRT, correcta, b7.77 (1.31)4.78 (1.72)5.22 (1.87)24.15
BVRT, errorsa, b2.95 (2.03)9.43 (3.70)8.53 (3.98)26.44
Boston naminga, b56.00 (3.07)49.52 (6.23)52.06 (4.70)11.67
Stroop 1a, b107.64 (10.38)77.22 (26.57)88.28 (19.33)14.80
Stroop 2a, b74.73 (10.96)56.76 (17.87)53.58 (13.85)14.34
Stroop 3a, b44.55 (7.57)33.89 (14.01)30.08 (12.32)9.62
ROCF: copya, b34.31 (1.46)30.53 (3.90)29.28 (4.79)11.70
ROCF: delaya, b2.06 (4.52)13.84 (6.15)13.51 (6.34)17.30
WCST-number of categoriesb, c5.05 (1.91)4.63 (1.24)2.56 (1.90)21.75
WCST-% perseverative responsesb, c12.04 (4.19)15.80 (10.89)29.17 (19.07)14.29

a Significant differences between NY and NE (P<0.05).

b Significant differences between NY and AIDS (P<0.05).

c Significant differences between NE and AIDS (P<0.05).

One-way ANOVA for neuropsychological tests yielded a significant main effect for all measures between younger controls and normal elderly (except on WCST) and AIDS patients. As Table 2 illustrates, this was the result of a significantly lower performance by both the normal elderly and the AIDS subjects as compared with the younger controls. Again, as can be seen in Table 2, no difference was found between the normal elderly group and the AIDS patients regarding these variables though both performed more poorly than the young normals, except on the Similarities subtest of WAIS and the WCST, where the performance of the normal elderly was superior to that of the AIDS patients.

Fig. 1 represents performance in the different neuropsychological tasks for each of the groups, after the direct scores were transformed to Z scores and their direction corrected. As can be seen in the graph, in the tasks in which the AIDS patients showed a poor performance, the normal elderly performed poorly as well, except in the WCST and the similarities subtest of WAIS where the AIDS patients had the greatest difficulty. On the other hand, while the normal elderly and AIDS patients did not differ with regard to these measures, both groups did show a worse performance than the young normals, except in the WCST on which the one-way ANOVA failed to find statistically significant differences among normal elderly and normal young subjects.

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4. Discussion 

This study reveals a remarkable similarity between the neuropsychological performance by the normal elderly and the much younger AIDS patients, despite great age differences between the groups (70.5 vs. 29.9 years). In contrast, both these groups showed neuropsychological test performances significantly different from those of the younger normal controls.

The young AIDS patients are neuropsychologically more similar to subjects more than twice their age than to the carefully matched younger controls, which leads us to pose that the neuropsychological changes associated with normal aging are of a similar nature to those observed in AIDS.

Along the same line as what can be seen in other studies (Van Gorp et al., 1989, Hinkin et al., 1990), our data reveal that the changes observed in the normal elderly and the AIDS patients involved attention, verbal and non-verbal recall, cognitive flexibility, visuospatial function, language and concept formation and reasoning, functions believed to be mediated by frontal lobe and subcortical structures. We also noted that the AIDS patients perform even more poorly than the normal elderly in tasks such as the WCST and similarities subtest of WAIS, both believed to be involved in the frontal lobe function. These findings suggest that the AIDS patients show greater frontal affection than the normal elderly as regards concept formation and reasoning, since we have even noted that in these tasks the performance of the normal elderly in our study is the same as that of the normal young.

The similarity of the neuropsychological performance of the normal elderly and the younger AIDS patients supports the frontal/subcortical hypothesis of neuropsychological aging, inasmuch as the pattern described for the AIDS patients is frontal–subcortical, as described in different studies (Navia et al., 1986, Post et al., 1991, Kent et al., 1994, Brew et al., 1995). Although our data support the hypothesis of a frontal dysfunction associated with aging, the poorer performance of the AIDS patients in the WCST as compared with the normal elderly and the fact that the latter do not differ statistically from the normal young in this task leads us to posit a lesser affection in concept formation and reasoning in normal aging than that associated with HIV infection.

The loss of neurons in the frontal cortex, cerebral atrophy and the demyelination of white matter, mainly in the periventricular zones, corpus callosum, internal capsule, anterior commissure and optic tract that have been described in AIDS patients (Everall et al., 1991, Martin, 1994) are similar to the changes in gray and white matter described in the normal elderly. Brain imaging has in fact confirmed dilation of cortical sulci and enlargement of ventricles with advancing age (DeCarli et al., 1990), and a decline in the cortical gray matter tissue density after age 60 (Meyer et al., 1994). Terry et al. (1987), using an image-analysis technique, found that the most prominent neuronal loss occurred in the frontal and parietal lobes. These lesions may contribute to neuropsychological changes in the course of aging and AIDS.

Much more research will be required to constructively integrate the complex cognitive changes observed in normal aging and AIDS with the knowledge base on changes in neurobiological aging and to relate neuropsychological findings to pathological and metabolic investigations.

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Archives of Gerontology and Geriatrics
Volume 36, Issue 1 , Pages 57-65, January 2003

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