Age-associated Memory Impairment Subjects Research Articles

Non-invasive localization of P300 sources in normal aging and age-associated memory impairment

Cognitive event-related potentials were recorded from 17 EEG leads in an auditory two-tone paradigm in 43 patients aged 51–79 years with the diagnosis of age-associated memory impairment (AAMI), in age-and sex-matched normal controls and in a control group 10 years older than the AAMI patients. In addition to P300 latencies, amplitudes and topographies, three-dimensional current density distribution utilizing low-resolution brain electromagnetic tomography (LORETA) was computed. P300 latency was delayed and P300 amplitude was reduced in both AAMI and older subjects. Topographically this amplitude reduction was most pronounced frontally. LORETA revealed medial (frontal and parietal) and lateral (dorso- and ventrolateral prefrontal, middle/superior temporal, posterior superior temporal/inferior parietal) sources. Significant reductions in LORETA source strength in normal aging and in AAMI were found mainly medially frontally, right dorsolaterally prefrontally and right inferiorly parietally. Since these anatomically highly interconnected brain regions in the right hemisphere are part of a network associated with sustained attention, the results speak for a decline in attentional resource capacity in AAMI patients and elderly subjects.

Angiotensin I converting enzyme polymorphism in humans with age-associated memory impairment: relationship with cognitive performance

We compared the distribution of an insertion (I)/deletion (D) polymorphism coding for the angiotensin I converting enzyme (ACE) gene in 100 subjects fulfilling NIMH criteria for Age-associated memory impairment (AAMI) and 124 controls. We found significantly reduced prevalences of the ACE I/I genotype together with increases of the ACE D allele in the AAMI group. We further compared the neuropsychological performance of the AAMI group according to their ACE genotype. Those AAMI subjects presenting the ACE I/I genotype exhibited better performance on a measure of frontal lobe function. Our results suggest that the lack of the ACE I/I genotype and the presence of the ACE D allele are associated with memory impairment in the elderly.

Age‐associated memory impairment—pathological memory decline or normal aging?

The aim of the study was to determine whether the memory capacity of individuals with age-associated memory impairment (AAMI) over a period of approximately 3 1/2 years declines more, if at all, than the memory capacity of persons without AAMI. Four computerized and three non-computerized memory tests, a naming test, and a test of visuo-motor speed were administered twice. Two estimates of intellectual capacity were made, one at the first examination and the other 3 1/2 years later. One person in the AAMI group (n = 44) developed vascular dementia. The group of AAMI subjects did less well on two of the seven memory tests after 3 1/2 years than they did initially; the control group (n = 18) had lower scores on one memory test at follow-up than they had previously. The data suggest that the memory capacity of subjects with AAMI is not pathologically impaired. The general intellectual level significantly influences whether an individual with memory complaints will be classified AAMI or not. People with high intelligence are less likely than people with lower intellectual capacity to fulfill the AAMI criteria. This suggests that AAMI lacks in construct validity.

MRI of the Hippocampus in Alzheimer’s Disease: Sensitivity, Specificity, and Analysis of the Incorrectly Classified Subjects

In this study, magnetic resonance imaging (MRI) of the hippocampus for the diagnosis of early Alzheimer’s disease (AD) is evaluated. We measured hippocampal volumes and the area of the medial hippocampus with a 1.5 T MR imager in 160 subjects: 55 patients with probable AD according to the NINCDS-ADRDA criteria, 43 subjects fulfilling the NIMH criteria of age-associated memory impairment (AAMI), 42 cognitively normal elderly controls, and 20 controls younger than 50 years. Three methods for normalization were compared. The hippocampi were atrophied in the AD patients, but not in the AAMI subjects or the elderly controls. There was no significant correlation between hippocampal volumes and age in the nondemented subjects. The discrimination based on volumetry resulted in an overall correct classification of 92% of AD patients vs. nondemented elderly subjects, whereas discrimination based on hippocampal area was less accurate, producing a correct classification in 80% of the subjects. We conclude that the hippocampus as assessed by MRI volumetry is atrophied early in AD, and spared by aging or AAMI. A brief critical review of previous studies is in concordance with the presented data: all the previous studies that have used volumetry, have similarly ended up with a good classification, whereas simpler or subjective measurements, subject to various sources of bias, have produced most variable results.

Decline of frontal lobe functions in subjects with age-associated memory impairment.

To assess frontal lobe functions of subjects with age-associated memory impairment (AAMI) and to examine whether performance on neuropsychological tests is correlated with the volume of the frontal lobes in magnetic resonance imaging. Cross-sectional two-group comparison. The Memory Research Clinic of Kuopio University and the Magnetic Resonance Imaging Center of Kuopio University Hospital. Ninety subjects (mean age, 70.5 years), 43 with AAMI diagnosed according to National Institute of Mental Health criteria and 47 age-matched healthy controls. Four neuropsychological tests were used to assess frontal lobe function: Verbal Fluency Test (VFT), Modified Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Stroop Test (ST). A 1.5-T magnetic resonance imager was used for volume measurements. The AAMI subjects scored significantly worse on the WCST, ST, and TMT compared with controls (ANCOVA, adjusted for age and education, p < 0.05). The frontal lobe volumes did not differ between AAMI subjects and controls. AAMI subjects appear to be impaired not only in tests assessing memory but also in tests of executive functions. This finding agrees with previous reports suggesting a central role for frontal dysfunction in memory loss of elderly people.

MR T 2 relaxometry in Alzheimer's disease and age-associated memory impairment

A prolonged MR T 2 relaxation time was proposed to mark the presence and severity of Alzheimer's disease (AD). We studied the value of T 2 relaxometry in diagnosing early AD. T 2 was measured from 54 patients with AD, 25 subjects with age-associated memory impairment (AAMI), 18 elderly and 16 young controls. The AD patients had longer T 2 in the right hippocampal head (104 ± 11 ms) and tail (98 ± 10 ms) than age-matched controls (95 ± 5 and 92 ± 9 ms, respectively). This prolongation was not related to age. In the AD group, the T 2 of the left hippocampal head also correlated with the clinical severity. The T 2 of the amygdala did not differ across the groups. Increased T 2 in the temporal and parietal white matter and the thalamus related to increasing age rather than to the diagnostic category. The AAMI subjects had T 2 comparable with those of age-matched controls. Despite the prolongation of T 2 in the AD group the possible diagnostic value was compromized by a substantial overlap between the study groups. We, thus, conclude that the T 2 relaxometry is not a reliable method for diagnosing early AD.

1H-MRS, MRI-based hippocampal volumetry, and 99mTc-HMPAO-SPECT in normal aging, age-associated memory impairment, and probable Alzheimer's disease.

To better understand how to differentiate the "in vivo" normal aging brain from pathological conditions, namely dementia of the Alzheimer type (DAT), by means of magnetic resonance imaging (MRI), single photon emission computerized tomography (SPECT), and proton magnetic resonance spectroscopy (1H-MRS), to show neuroanatomical, perfusional and neurochemical details, respectively. 1H-MRS, MRI-based hippocampal volumetry and 99mTc-HMPAO SPECT were performed in healthy older subjects as well as patients suffering from age-associated memory impairment (AAMI) and dementia of Alzheimer type (DAT). Eighteen subjects were selected from those referred to an outpatient clinic for diagnostic evaluation of cognitive impairment entered the study. Six patients fulfilled NINCDS-ADRDA diagnostic criteria for DAT, six subjects were affected by AAMI, and six cognitively healthy subjects, selected from among relatives of the patients, were defined as controls. The 1H-MRS and MRI studies were performed on a 1.5 Tesla NMR-imaging system equipped with a spectroscopy research package. SPECT scans were performed on a Gamma 11 computer system. 1H-MRS showed significantly lower N-acetylasparatate concentration in DAT and AAMI compared with controls. Conversely, mean inositol concentration was significantly higher in DAT than in controls, whereas AAMI subjects registered intermediate values. MRI measurements showed significantly reduced volumes of hippocampal formations in DAT and AAMI groups compared with controls. Finally, 99mTc-HMPAO SPECT showed a significant frontal, temporo-parietal, and occipital hypoperfusion in DAT patients only. These findings support the hypothesis of a continuum among the three conditions studied, or at least between AAMI and DAT, where AAMI seems to be an early, monosymptomatic stage of Alzheimer disease. Accepting this view, it would be questionable to maintain the term "age-associated memory impairment" as a discrete entity.

A follow-up study of age-associated memory impairment: neuropsychological predictors of dementia.

To examine the clinical course of age-associated memory impairment (AAMI) and to evaluate the value of neuropsychological tests in predicting cognitive decline in AAMI subjects in a follow-up period of more than 3 years. Prospective cohort study. The outpatient Memory Research Unit of the Department of Neurology at the University of Kuopio in Eastern Finland. A sample of 229 subjects (mean age 71.7 years) identified in two screening studies as having AAMI. A battery of neuropsychological tests and a structured inquiry for health status and subjective memory complaints were performed at baseline and follow-up to diagnose AAMI according to the criteria proposed by a National Institute of Mental Health work group. Of the 229 subjects, 176 (76.9%) participated in the follow-up for, on average, 3.6 years after the baseline. Of the participants, 104 (59.1%) still met the AAMI criteria. Other subjects were classified into five subgroups: (1) subjects showing decline in cognition meeting dementia diagnosis (16, 9.1% (13 of them AD)); (2) subjects with mild cognitive decline meeting neither dementia nor AAMI criteria (13, 7.4%); (3) subjects with memory performance now superior to AAMI criteria (17, 9.7%); (4) subjects having a disease classified as exclusion in the criteria (15, 8.5%); (5) subjects not now reporting subjective memory loss in everyday life (9, 5.1%). Two subjects (1.1%) were not classified because of incomplete data. Neuropsychological tests predicted which subjects would develop dementia during the follow-up period. The best discriminators between these subjects and those who remained AAMI were memory and verbal fluency tests. The study suggests that, in general, AAMI is nonprogressive, but the AAMI population also includes subjects with early dementia and subjects without genuine memory loss. However, these subjects can be differentiated with a more detailed neuropsychological evaluation.

Habituation of auditory N100 correlates with amygdaloid volumes and frontal functions in age-associated memory impairment

We studied the habituation of auditory N100 responses in subjects with age-associated memory impairment (AAMI) and in healthy age-matched volunteers. The findings were correlated with volumes of the amygdala, hippocampus, and frontal lobe measured by magnetic resonance imaging (MRI), as well as with subjects' performance on tests assessing frontal lobe functions and memory. Habituation of N100 did not differ aacros AAMI subjects and controls. However, in AAMI subjects there was a significant correlation between habituation of N100 and volumes of the amygdala; the more reduced habituation, the smaller volume. In addition, decline in habituation of N100 correlated with impaired performance on a visual memory test (Heaton Visual Retention) Test; r = 0.77; p < 0.001) and impairment on tests assessing frontal functions (Verbal Fluency, Trail Making Test, and Stroop). Habituation of N100 was not related to age or sex. To our knowledge this is the first study to demonstrate a relationship between habituation of evoked responses, MRI volumetric measures, and performance on psychometric tests. The results suggest that impaired memory and frontal lobe functions in AAMI subjects may be associated with poor habituation of N100. Since habituation reflects focusing of attention to relevant features of stimuli, impairment of this mechanism and subsequent defective memory trace formation may contribute to the observed deficits on memory tests.

Volumetric MRI analysis of the amygdala and the hippocampus in subjects with age-associated memory impairment: correlation to visual and verbal memory.

Age-associated memory impairment (AAMI) is a common but disputed entity. It is unclear whether AAMI is a phenomenon of normal aging or an early sign of Alzheimer's disease. The present study aimed to identify possible structural abnormalities in the medial temporal lobe of AAMI subjects. We measured volumes of the hippocampus and amygdala by MRI in 16 AAMI subjects and in 16 age- and sex-matched controls and correlated the volumes with subjects' performance on two visual memory tasks (the Benton and the Heaton visual retention tests) and on a verbal memory task (the Buschke-Fuld Selective Reminding Test). The mean hippocampal and amygdaloid volumes normalized for brain size per se did not differ between the two study groups. In controls, but not in AAMI subjects, the right hippocampus was larger than the left. Accordingly, the volumetric asymmetry between the right and left hippocampi was smaller in AAMI subjects than in controls (Student's t test, p < 0.05). The volume of the right hippocampus (r = 0.37, n = 32, p < 0.05) and the magnitude of the asymmetry between the right and left hippocampi (r = 0.38, n = 32, p < 0.05) correlated with total score on the Benton test. We also found significant correlations between the amygdaloid volumes and the performance on visual memory tests but not with score on the verbal memory test.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating immune complexes in sera from patients with Alzheimer's disease and subjects with age-associated memory impairment.

Before, we reported a higher frequency of circulating immune complexes (CIC) in the sera from institutionalized Alzheimer's disease (AD), multi-infarct dementia and Down's syndrome patients than from age-matched controls. In this study, we tested the presence of CIC in the sera from an extended series of hospitalized AD patients, AD patients living in the community, from age-associated memory impairment (AAMI) subjects as well as from nursing home and community controls. We used two methods to measure CIC, C1q binding Elisa (C1qB-Elisa) and conglutinin binding (KgB-Elisa). The AD patients showed the highest frequency of positive findings and differed from the controls in KgB (42% vs. 17%) (Chi-square, p = 0.01) and C1qB (30% vs. 11%) (p < 0.05). In severe AD, 14/19 patients were KgB positive and 11/19 were C1qB positive and differed from controls. The frequency of CIC for the patients with moderate or mild dementia, the AAMI subjects and controls was similar. In the multivariate linear regression analysis, high CIC values of the AD patients significantly associated with a long disease duration and a history of recurrent urinary infections but not with age, sex, hospitalization, or the Mini-Mental Status score. We conclude that AD patients with severe dementia frequently show CIC but those with mild or moderate disease do not. The CIC relate to a long disease duration and a history of recurrent urinary infections.