Jaap Lindeboom

Subjective memory complaints may announce dementia

Article abstract-Whether subjective memory complaints in the absence of objective memory decline can predict future dementia has been investigated only in highly selected clinical and volunteer cohorts. Our study examines this question in a subsample of AMSTEL (Amsterdam Study of the Elderly), a longitudinal population study on cognitive decline and dementia. Subjects (aged 65 to 84 years; n = 357) without dementia or other psychiatric disorders at baseline were followed for 3 years. After this interval, 16 of 203 re-examined patients developed a dementia. Logistic regression analyses indicated that memory complaints at baseline contributed a small but significant amount of diagnostic information. However, the most powerful predictor of future dementia was deficient memory performance. We conclude that subjective memory complaints may predict dementia within 3 years, particularly when there are objective signs of memory deterioration. NEUROLOGY 1996;46: 121-125

Visual association test to detect early dementia of the Alzheimer type

Background: The visual association test (VAT) is a brief learning task based on imagery mnemonics. The test materials consist of six line drawings of pairs of interacting objects or animals—for example, an ape holding an umbrella. The person is asked to name each object and, later, is presented with one object from the pair and asked to name the other. Objective: To verify that the task induces robust incidental or effortless learning (study 1), and to study the efficiency of the test as a discriminator between early dementia of the Alzheimer type (DAT) and non-demented people (study 2) and non-DAT types of dementia (study 3). Methods: Study 1: two groups of elderly volunteers were administered the VAT. The stimuli were presented in the interactive fashion to group A—for example, a monkey carrying an umbrella (n=83)—and side by side to group B—for example, separate pictures of a monkey alone and an umbrella alone (n=79). Group B received learning instructions, but group A did not. Study 2: three groups of subjects were selected from a population based follow up study: incident DAT cases (n=24), cognitively declining subjects not diagnosed with dementia (n=21), and stable non-demented subjects (n=204). Test performance of the non-demented group at baseline was compared with that of patients with DAT at the time of their diagnosis, of patients with DAT a year before their diagnosis, and of non-demented declining subjects at baseline. Study 3: subjects were patients referred for neuropsychological assessment because of suspected dementia. They were diagnosed by consensus criteria of various dementia syndromes. Results: Study 1: recall was more than twice as high in group A as in group B. Thus interactive presentation, even in the absence of learning instructions, enhances learning. Study 2: at a level of 97.5% specificity, the VAT had a sensitivity of 87.5% for DAT cases at the time of diagnosis and 66.7% one year before diagnosis. The cognitively declining group scored significantly lower on the VAT at baseline than the non-demented group. The VAT discriminated more effectively than both the MMSE and the six item picture learning task from the CAMCOG. Study 3: VAT scores were significantly lower in patients with DAT (n=48) than in patients with vascular dementia (n=37), frontotemporal dementia (n=9), or subcortical dementia (n=15), but not lower than in patients with Lewy body dementia (n=7). Mean mini mental state examination scores of these groups were not significantly different. The VAT discriminated patients with DAT from patients with other types of dementia more effectively than a prose recall test. Sensitivity was 79% and specificity 69%. Conclusions: The VAT detects with high specificity a sizeable proportion of patients with DAT a year before the diagnosis, and a low VAT score is relatively uncommon in patients with non-DAT dementia.

Memory Complaints and Memory Impairment in Older Individuals

OBJECTIVE: To examine whether subjective memory complaints, measured with a series of four questions, are associated with performance on cognitive tests.

Visual association encoding activates the medial temporal lobe: a functional magnetic resonance imaging study

The involvement of structures in the medial temporal lobe during the encoding of visual associations was studied with functional magnetic resonance imaging. In 11 out of 12 normal healthy volunteers this task resulted in activation in posterior portions of the parahippocampal region, close to the collateral sulcus. In seven subjects activation was encountered in the hippocampal formation. The visual association task as adapted for this study may provide a sensitive measure to study anterograde amnesia prevalent in Alzheimers disease. Therefore, the present paradigm enables the study of individual changes in learning and memory capacities over time. Hippocampus 1997;7:594–601.

Neuropsychological correlates of a right unilateral lacunar thalamic infarction

OBJECTIVES To report on a patient with a lacunar infarction in the right intralaminar nuclei of the thalamus. The role of the thalamic intralaminar nuclei in cognitive function is as yet insufficiently known. The patient described has shown signs of apathy and loss of initiative, in combination with cognitive deficits, which have persisted essentially unaltered up to the present day since an abrupt onset 17 years ago. METHODS High resolution MRI was performed to show the extent of the lesion; a combination of published and experimental neuropsychological techniques was administered to show the nature of the cognitive defects; Single photon emission computed tomography (SPECT) was employed to obtain a measure of cortical perfusion. RESULTS Brain MRI disclosed an isolated lacunar infarction in the dorsal caudal intralaminar nuclei of the thalamus. Neuropsychological evaluation indicated problems with attention and concentration, executive disturbances, and memory deficits both in the visual and verbal domains. The memory deficits could not be attributed to problems in the early stages of information processing, and are hence regarded as resulting from a failure of retrieval rather than encoding or storage. Brain SPECT disclosed a hypoperfusion of the right frontal cortex. CONCLUSION The data indicate that the cognitive profile is the result of a dysfunction of executive functions. This is corroborated by the finding of decreased blood flow in the right frontal cortex, and by evidence from the neuroanatomical literature. Thus the dysexecutive symptoms are thought to be caused by disconnection of the prefrontal cortex from the brainstem activating nuclei through the strategic localisation of the right thalamic infarction.

Amsterdam short-term memory test: A new procedure for the detection of feigned memory deficits

The validity of two malingering tests, the newly developed Amsterdam Short-Term Memory (ASTM) test and the Distraction test (Baker, Hanley, Jackson, Kimmance, & Slade, 1993) was examined in a group of patients with closed-head injury (CHI), a normal control group, and a control group with instruction to feign memory deficits. Both control groups consisted of first-degree relatives of the patients. The ASTM test is a forced-choice verbal memory test, based on the technique of symptom validity testing. Stimulus material was chosen from category norms and chance level is not transparent. The CHI and normal control groups scored near ceiling on the ASTM test, whereas the feigned deficit group scored significantly worse. The ASTM test classified all subjects correctly. Contrary to expectation, the Distraction test appeared to be invalid. The score profiles of the CHI and feigning groups on conventional memory and concentration tests were indistinguishable from each other. Thus, the ASTM test may be very useful for the detection of malingering and other kinds of less than optimal performance. The test may readily be constructed in any language for which category norms are available.

Early detection of Alzheimer's disease using the Cambridge Cognitive Examination (CAMCOG).

BACKGROUND Dementia screening instruments, such as the Cambridge Cognitive Examination (CAMCOG), measure a variety of cognitive functions. However, memory impairment generally is the first sign of Alzheimers disease (AD). It seems logical, therefore, to use only memory-related items for the early detection of AD. We divided the CAMCOG into a memory section and a non-memory section, and tested the hypothesis that the memory section predicts AD better than the non-memory section. We also provide normative data for both sections. METHODS Normal subjects (N = 169) and patients with incident AD (i.e. satisfying AD criteria between 1 and 3 years from baseline: N = 25) were participants in the Amsterdam Study of the Elderly (AMSTEL), a population-based longitudinal study on cognitive decline and dementia. Patients with prevalent AD (i.e. satisfying AD criteria at baseline: N = 155) were either recruited in a memory clinic or came from AMSTEL. Normal subjects were cognitively intact at baseline and remained so for at least 3 years. The CAMCOG was administered to all subjects. AD was diagnosed by DSM-III-R criteria. RESULTS Logistic regression analysis showed that the memory section was related to prevalent AD, whereas in multivariate analysis the non-memory section was not (after correction for the memory score and demographic characteristics). A similar analysis showed that the memory section predicted incident AD, as did a higher score on the non-memory section. The MMSE did not predict incident AD better than age alone. CONCLUSION For the early detection of AD it is best to use the memory and non-memory sections separately instead of the total CAMCOG score.

Biomarker profiles and their relation to clinical variables in mild cognitive impairment

The aim of the study was to compare clinical variables between MCI patients at different risk for Alzheimer’s disease (AD) according to their biomarker profile. Fifty-four percent out of 39 MCI patients had a low Aβ42 and high tau in cerebrospinal fluid (CSF) (high-risk), 26% either a low CSF Aβ42 or high CSF tau (intermediate-risk) and 20% a normal CSF Aβ42 and tau (low-risk). Both high- and intermediate-risk subjects differed from the low-risk group in episodic memory, executive functions and the preclinical AD scale (PAS), which combines a set of clinical parameters. Subjects at high risk did not differ from subjects with an intermediate risk. Aβ42 levels correlated with the MTA and PAS scores, tau levels with episodic memory. These correlations suggest that the biomarkers are not independent when compared to the other AD markers. Longitudinal studies are necessary to interpret the correlations between biomarkers, imaging, and neuropsychological markers.

Increased risk of mortality in Alzheimer's disease patients with higher education? A replication study

The objective of this study was to replicate findings from an earlier study by Stern et al. of an increased risk of mortality in Alzheimers disease (AD) patients with higher levels of education and to compare this risk with the risk of death in the elderly population. As part of a community-based follow-up study on dementia (Amsterdam Study of the Elderly[AMSTEL]) a cohort of 4,051 noninstitutionalized elderly age 65 to 84 years stratified in four 5-year strata of equal size was screened for dementia using the MMSE (Mini-Mental State Examination). Those suspected of dementia received diagnostic evaluation using the CAMDEX (Cambridge examination for mental disorders in the elderly). Clinical diagnoses of probable AD were made according to NINCDS-ADRDA criteria. Thirty-six prevalent patients were diagnosed as having AD. The suspected subcohort was followed up yearly over a period of 4 years. During the three yearly follow-ups, 30 incident patients received a diagnosis as well. After 6 years mortality data were obtained from municipality records. Cox proportional hazards models adjusted for age and sex were used to estimate the relative risk of death associated with the level of education. Relative risk of death decreased (although not statistically significant) in AD patients as level of education increased (RR= 0.86; 95% CI, 0.63 to 1.19). In the full baseline sample, relative risk of death decreased as level of education increased (RR = 0.86; 95% CI, 0.89 to 0.97). In this study we could not replicate the findings of Stern et al. of an increased risk of death in more highly educated AD patients. Several major differences between the two studies, among which difference in populations used is considered to be most important, are discussed that might explain the conflicting results. We conclude that higher education is not associated with increased risk of mortality in AD patients.

Late-life depressive disorder in the community, early onset and the decrease of vulnerability with increasing age

This study examined reports of a history of psychiatric illness related to age and depression in 4051 community residents aged 65-84. Depression was twice as common among subjects with a history of psychiatric illness before age 65. 78% of depressed subjects reported no history. The rate of reported history was inversely proportionate to the subjects actual age. This did not appear to be due to recollection bias but it did match the proportions previously reported to result from excess mortality of individuals with a psychiatric history. A psychiatric history may be an important risk factor for late-life depression but in the aging process after age 65 it may become increasingly uncommon.