The validity of new memory complaints in the elderly

OBJECTIVE: To determine the validity of new subjective memory complaints (MCs) from individuals who previously, when without dementia, denied having MCs. DESIGN: Prospective cohort. SETTING: Longitudinal, community-based study of aging and dementia. PATIENTS: One hundred thirty-three community-dwelling elderly individuals who were part of a registry for the study of conditions related to aging in North Manhattan, NY. Patients were selected if they were initially without dementia and had completed at least 2 successive annual clinical and neuropsychological evaluations and provided their own medical history. MAIN OUTCOME MEASURES: Performance on memory tests--the Buschke Selective Reminding Test and a visual memory task--and global performance on a neuropsychological test battery and clinical evaluation, by which questionable dementia or dementia was diagnosed according to a well-defined paradigm. RESULTS: Fifty-three subjects with MCs at the initial evaluation performed no worse on the memory test than the 80 subjects who denied MCs initially. There was a weak association between MCs and the diagnosis of questionable dementia at baseline (P = .04), but this was nonsignificant after adjusting for age and education. At 1-year follow-up, 21 of the 80 without baseline MCs now reported MCs. At the follow-up evaluation, these 21 subjects performed significantly worse on the memory tests, were 5 times more likely to have significant cognitive impairment, and had shown significantly greater decline over the preceding year on several of the cognitive measures than the 59 who continued to deny MCs. CONCLUSION: New MCs from individuals, who when without dementia recently denied MCs, may suggest the presence of significant impairment of memory or cognition.     

A four year prospective study of age-related cognitive change in adults with Down's syndrome

BACKGROUND: While neuropathological studies indicate a high risk for Alzheimer's disease in adults with Down's syndrome, neuropsychological studies suggest a lower prevalence of dementia. In this study, cognitive deterioration in adults with Down's syndrome was examined prospectively over 4 years to establish rates and profiles of cognitive deterioration. METHODS: Fifty-seven people with Down's syndrome aged 30 years or older were assessed using a battery of neuropsychological tests on five occasions across 50 months. Assessments of domains of cognitive function known to change with the onset of Alzheimer related dementia were employed. These included tests of learning, memory, orientation, agnosia, apraxia and aphasia. The individual growth trajectory methodology was used to analyse change over time. RESULTS: Severe cognitive deterioration, such as acquired, apraxia and agnosia, was evident in 28.3% of those aged over 30 and a higher prevalence of these impairments was associated with older age. The rate of cognitive deterioration also increased with age and degree of pre-existing cognitive impairment. Additionally, deterioration in memory, learning and orientation preceded the acquisition of aphasia, agnosia and apraxia. CONCLUSIONS: The prevalence of cognitive impairments consistent with the presence of Alzheimer's disease is lower than that suggested by neuropathological studies. The pattern of the acquisition of cognitive impairments in adults with Down's syndrome is similar to that seen in individuals with Alzheimer's disease who do not have Down's syndrome.     

Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance

Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities.     

Predictors of longitudinal changes in memory, visuospatial, and verbal functioning in very old demented adults

Longitudinal changes in memory, visuospatial and verbal functioning in a sample of demented persons were examined. The role of several demographic, psychometric, and biological indices in predicting the rate of cognitive deterioration was also investigated. The sample consisted of 31 very old (mean age at entry = 83.5 years, range = 75-95) persons with Alzheimer's disease (n = 22) and vascular dementia (n = 9) from a community-based study. Subjects were tested on two occasions separated by approximately 2.5 years. Results indicated significant longitudinal decline in verbal fluency and visuospatial ability, but only on 1 of 3 measures of episodic memory. Results from regression analyses indicated that a variety of putatively important variables, including age, gender, education, digit span, as well as a number of biological (vitamin B12, TSH), dementia etiology, and psychometric (digit span) indicators, exhibited no relationship to rate of memory, visuospatial, or verbal decline. The results suggest that the rate of cognitive deterioration in dementia is highly variable, and this variability in change appears to include a variety of characteristics. A possible reason thereof may be that the role of individual-difference variables for cognitive functioning in dementia is overshadowed by the pathogenetic process itself.     

Fluency and memory differences between ischemic vascular dementia and Alzheimer's disease.

This study compared 32 patients with ischemic vascular dementia (IVD) to 32 patients with probable Alzheimer's disease (AD) on select language and verbal memory tests. The IVD and AD patients were individually matched on the basis of age, dementia severity, years of education, and gender. The IVD patients had poorer verbal fluency, but better free recall, fewer recall intrusions, and better recognition memory than the AD patients. Relationships between the neuropsychological measures and radiological indexes of cortical and subcortical pathology were also examined. Number of infarcts, white-matter lucency, and ventricular enlargement correlated with some of the neuropsychological measures; cortical atrophy correlated with most of the measures. The findings suggest that neuropsychological deficits in IVD may be related to dysfunction of frontal-subcortical circuits, although an associated degenerative cortical process may also be involved. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use of IQ-Adjusted Norms to Predict Progressive Cognitive Decline in Highly Intelligent Older Individuals.

Identifying high-functioning older individuals in preclinical phases of Alzheimer's disease (AD) may require more sensitive methods than the standard approach. The authors explored the utility of adjusting for premorbid intelligence to predict progressive cognitive decline or Mild Cognitive Impairment (MCI) in 42 highly intelligent older individuals. When scores were adjusted for baseline IQ, 9 participants had executive impairments, 11 had memory impairments, and 22 scored in the normal range. None were impaired according to standard age norms. Three and a half years later, 9 participants with IQ-adjusted memory impairment declined in naming, visuospatial functioning, and memory; 6 convened to MCI. Three participants with normal memory declined. Implications for using IQ-adjusted norms to predict preclinical AD are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia

OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimer's disease; patients with Alzheimer's disease showed more severe anosognosia and disinhibition than patients with Parkinson's disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinson's disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimer's disease. CONCLUSION: There were significant psychiatric differences between patients with Alzheimer's disease and demented patients with Parkinson's disease, but neuropsychological differences were restricted to a single cognitive domain.     

Influences of preclinical dementia and impending death on the magnitude of age-related cognitive deficits.

The authors examined the influence of preclinical dementia and impending death on the cross-sectional relationship between age and performance in tasks assessing episodic memory, visuospatial skill, and verbal fluency. Increasing age was associated with a general decrease in cognitive performance. In addition, those who were to be diagnosed with dementia had died by a 3-year follow-up, were older, and performed at a lower level than the remaining sample across all cognitive tasks at baseline. Nevertheless, removal of the preclinical dementia and impending death groups from the original sample affected the cross-sectional age-cognition relations relatively little. This pattern of findings suggests that the biological aging process exerts negative influences on cognitive functioning beyond those resulting from disease and mortality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glucose effects on cognition in adults with Down's syndrome.

Glucose enhances memory in a variety of individuals, including people with Alzheimer's disease. By 35 years of age, adults with Down's syndrome (DS) develop the characteristic plaques and tangles found in Alzheimer's disease, despite findings indicating that not all older DS individuals meet criteria for dementia. To examine the possibility that glucose enhances memory in adults with DS (mean age?=?35 years, range?=?19–55 years), adults with DS were given a battery of tests specifically designed for individuals with DS in glucose and control conditions. No participant met criteria for dementia, regardless of age. Glucose enhanced performance on tests requiring both long-term memory and auditory processing. In addition, increased age was associated with poorer performance on the majority of tests in the control condition, indicating that cognitive decline with aging may be more prevalent in DS than previously believed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context Processing and Context Maintenance in Healthy Aging and Early Stage Dementia of the Alzheimer's Type.

Declines in the ability to process context information may represent a fundamental mechanism of age-related cognitive changes. Two components of context processing--activation/updating and maintenance--were examined in a sample of healthy younger and older adults, along with individuals suffering from early stage dementia of the Alzheimer's type (DAT). All older adult groups showed context activation/updating impairments, whereas context maintenance was only impaired in the oldest adults (age>75 years) and was further exacerbated in DAT individuals. The results suggest that context processing may be composed of functionally dissociable components and point to the utility of this construct in understanding the timecourse of cognitive decline in healthy and pathological aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low education is a genuine risk factor for accelerated memory decline and dementia

A relatively high prevalence and incidence of dementia have been found in population strata with low levels of education in comparison to population strata with high levels of education. However, doubt remains whether this may be an artifact of education bias in the screening tests used. To investigate this matter, we analyzed results of two Dutch population surveys in which unbiased measures of memory decline were used. In the Longitudinal Aging Study Amsterdam (n = 1774) the percentage of words retained in a verbal learning test was found to be disproportionately low in the oldest age cohort (80-85 years) with less than 11 years of education. The Amsterdam Study of the Elderly (n = 4051) found a "dose-response" relationship between education and dementia prevalence. Cross-sectional and longitudinal results showed that, in less educated people, memory decline is faster and sets in at an earlier age. These findings indicate that the relationship between dementia and education is not just an artifact of case detection methods.     

Effects of sequential neuropsychological testing of an elderly community-based sample

The magnitude and importance of changes in scores of neuropsychological tests on retest in the elderly, especially over long time periods, is not well established. Three neuropsychological tests and one mental status test were initially administered to screen for potential dementia and were readministered to 380 of the surviving individuals 2.4 years later who either failed the screening examination or were an age matched control. Of the 380 women and men aged 65 and older, 56 were diagnosed as having Alzheimer disease (AD), 82 as at risk for developing AD, and 242 as having normal cognition. The present report focuses on changes in test scores between the two visits. In the normal and at risk groups, significant improvements were seen on retest of the Visual Reproduction Test (VRT), the Trails B test, and the Mini-Mental Status examination; verbal fluency decreased, and savings score of the VRT showed small variations. On most tests, scores of the AD group decreased. Practice effects, biases, and other variables may have played a role in the improvements seen in those labeled normal and at risk. If these results are confirmed, savings score of the VRT (which remained stable over time in normals and individuals at risk and decreased in patients with dementia) and verbal fluency (which decreased in all groups) may be better measures of true cognitive performance than the other tests that we evaluated.     

Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study

BACKGROUND: Previous studies suggested a protective effect of smoking on Alzheimer's disease, but most were case-control studies based on prevalent cases. The findings of prospective studies on the association between smoking and the risk of dementia are inconclusive. METHODS: We did a population-based follow-up study of elderly people who were initially free of dementia. 6870 people aged 55 years and older agreed to take part. Smoking history was taken at baseline and participants were classified as never smokers, former smokers, and current smokers. During follow-up, we recorded all incident cases of dementia. We used never smokers as the reference category to calculate relative risks of dementia and Alzheimer's disease by Cox proportional hazards regression, after adjustment for age, sex, education, and alcohol intake. We also examined modification of risk by age, sex, and the apolipoprotein E (APOE) genotype. FINDINGS: During mean follow-up of 2.1 (range 1.5-3.4) years, 146 incident cases of dementia were detected, of which 105 were Alzheimer's disease. Compared with never smokers, smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6]) and Alzheimer's disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for Alzheimer's disease in individuals without the APOEepsilon4 allele (4.6 [1.5-14.2]), but had no effect in participants with this allele (0.6 [0.1-4.8]). INTERPRETATION: Smoking was associated with a doubling of the risk of dementia and Alzheimer's disease. Our finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APOEepsilon4 genotype in the aetiology of Alzheimer's disease.     

Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment.

Objective: Mild cognitive impairment (MCI) has emerged as a classification for a prodromal phase of cognitive decline that may precede the emergence of Alzheimer's disease (AD). Recent research suggests that attention, executive, and working memory deficits may appear much earlier in the progression of AD than traditionally conceptualized, and may be more consistently associated with the later development of AD than memory processing deficits. The present study longitudinally tracked attention, executive and working memory functions in subtypes of MCI. Method: In a longitudinal study, 52 amnestic MCI (a-MCI), 29 nonamnestic MCI (na-MCI), and 25 age- and education-matched controls undertook neuropsychological assessment of visual and verbal memory, attentional processing, executive functioning, working memory capacity, and semantic language at 10 month intervals. Results: Analysis by repeated measures ANOVA indicate that the a-MCI and na-MCI groups displayed a decline in simple sustained attention (ηp2 = .054) with a significant decline on a task of divided attention (ηp2 = .053) being evident in the a-MCI group. Stable deficits were found on other measures of attention, working memory and executive function in the a-MCI and na-MCI groups. The a-MCI group displayed stable impairments to visual and verbal memory. Conclusions: The results indicate that a-MCI and na-MCI display a stable pattern of deficits to attention, working memory, and executive function. The decline in simple sustained attention in a-MCI and n-MCI groups and to divided attention in a-MCI may be early indicators of possible transition to dementia from MCI. However, further research is required to determine this. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Cognitive predictors of incident Alzheimer's disease: A prospective longitudinal study.

The present study examined whether cognitive variables measured at baseline could predict incident cases of Alzheimer's disease (AD) after a 3-year follow-up period. Twenty-six incident AD adults and 179 very old (M?=?83.5 years) adults without dementia participated in a population-based study. Cognitive performance was indexed by the Mini-Mental State Examination (MMSE) and multiple indices of memory and visuospatial and verbal performance. A logistic regression analysis that controlled for age, gender, and education indicated that MMSE scores were reliable indicators of who would develop AD. In addition, recall of organizable words, recognition of faces, and letter fluency were reliable predictors of subsequent dementia status after differences in MMSE performance were partialed out. Thus, although the MMSE is useful in predicting dementia, there is an additional advantage of assessing specific indices of cognitive functioning. Further, supportive episodic memory tasks may be more salient predictors of incident AD than tasks that offer less supportive encoding or retrieval conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association between apolipoprotein E epsilon4 and the rate of cognitive decline in community-dwelling elderly individuals with and without dementia

OBJECTIVE: To determine whether the apolipoprotein E epsilon4 allele (apoE epsilon4) is associated with cognitive decline in individuals with and without dementia, we conducted a 4-year longitudinal study of subjects with a range of cognitive function. SETTING: At baseline, respondents (n=511) were randomly selected according to age and Mini-Mental State Examination score from a community-based study of dementia among noninstitutionalized persons aged 65 to 84 years. Respondents were examined at baseline and followed up in 3 annual visits. At baseline, subjects were classified as having normal cognitive function, minimal dementia, or dementia, according to criteria from the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Of the 511 respondents at baseline, 405 who were examined at least 2 times are included in this analysis. MAIN OUTCOME MEASURES: Cognitive decline was determined by a slope estimating yearly change in score on the neuropsychological test, the CAMCOG (the cognitive section of the CAMDEX), and its sub-scales of memory and nonmemory functions. RESULTS: Among the subjects who had normal cognitive function at baseline, apoE epsilon4 carriers showed a significantly greater decline (P<.001) in score on the CAMCOG compared with noncarriers. Differences in decline on the memory and nonmemory subtests were also significant (P<.001). Rates of cognitive decline were not related to apoE epsilon4 status in the groups with minimal dementia and dementia. CONCLUSIONS: In our community-based sample, apoE epsilon4 was associated with the rate of cognitive decline prior to the clinically symptomatic phase of dementia. Knowing the apoE epsilon4 status of those already symptomatic for dementia may not improve knowledge about a patient's prognosis.     

Comparison of neuropsychological functioning in Alzheimer's disease and frontotemporal dementia

Neuropsychological changes distinguishing mild Alzheimer's disease (AD) from frontotemporal dementia (FTD) have been described, but empirical verification of differential cognitive characteristics is lacking. Archival neuropsychological data on 15 FTD patients, 16 AD patients, and 16 controls were compared. Controls outperformed both patient groups on measures of verbal and nonverbal memory, executive ability, and constructional skill, with AD patients showing more widespread memory decline. No differences were found between the 3 groups in confrontation naming, recognition memory, or basic attention. Patient groups differed only in nonverbal memory, with FTD patients performing significantly better than AD patients. However, patient groups also differed in pattern of performance across executive and memory domains. Specifically, AD patients exhibited significantly greater impairment on memory than executive tasks, whereas the opposite pattern characterized the FTD group. These findings suggest that examination of relative rankings of scores across cognitive domains, in addition to interpretation of individual neuropsychological scores, may be useful in differential diagnosis of FTD versus AD.     

The differentiation of semantic dementia and frontal lobe dementia (temporal and frontal variants of frontotemporal dementia) from early Alzheimer's disease: A comparative neuropsychological study.

The authors compared age-matched groups of patients with the frontal and temporal lobe variants of frontotemporal dementia (FTD; dementia of frontal type [DFT] and semantic dementia), early Alzheimer's disease (AD), and normal controls (n?=?9 per group) on a comprehensive neuropsychological battery. A distinct profile emerged for each group: Those with AD showed a severe deficit in episodic memory with more subtle, but significant, impairments in semantic memory and visuospatial skills; patients with semantic dementia showed the previously documented picture of isolated, but profound, semantic memory breakdown with anomia and surface dyslexia but were indistinguishable from the AD group on a test of story recall; and the DFT group were the least impaired and showed mild deficits in episodic memory and verbal fluency but normal semantic memory. The frontal and temporal presentations of FTD are clearly separable from each other and from early AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling Memory Decline in Older Adults: The Importance of Preclinical Dementia, Attrition, and Chronological Age.

This longitudinal study examined memory loss in a sample of 391 initially nondemented older adults. Analyses decomposed observed memory loss into decline associated with preclinical dementia, study attrition, terminal decline, and chronological age. Measuring memory as a function of only chronological age failed to provide an adequate representation of cognitive change. Disease progression accounted for virtually all of the memory loss in the 25% of the sample that developed diagnosable dementia. In the remainder of the sample, both chronological age and study attrition contributed to observed memory loss. These results suggest that much of memory loss in aging adults may be attributable to the progression of preclinical dementia and other nonnormative aging processes that are not captured by chronological age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of proteins that interact with the IL-2 regulatory region in patients with rheumatic diseases

Bone marrow transplantation (BMT) involves conditioning with cyclophosphamide and, for leukemic patients, total body irradiation (TBI). Based on the concern that this may lead to later neuropsychologic impairment in children, a longitudinal study was conducted. Thirty pediatric bone marrow transplant recipients, treated for leukemia or severe aplastic anemia (SAA), and their sibling donors, were given a neuropsychological examination in 1986 and 1988. A third follow-up study of patients treated before 12 years of age was undertaken in 1990-91. We present longitudinal data on patients treated with BMT when 3-11 (n = 15) and 12-17 (n = 11) years old. No neuropsychological deficits were found in the older group, or among non-irradiated SAA patients. In the first follow-up, children treated with BMT, including TBI at 3-11 years of age, performed less well than donors on tasks involving perceptual and fine-motor speed. In the second follow-up, this group of patients also demonstrated a slight deficit in non-verbal problem solving. An additional relative decline in verbal reasoning was noted in the third follow-up, 5.5-10 years after treatment. Alertness to signs of developmental difficulties in children treated with BMT, including TBI, is recommended.