Memory evaluation in Alzheimer's disease. Caregivers' appraisals and objective testing

OBJECTIVES: To evaluate if caregivers are reliable informants concerning memory deficits in patients with Alzheimer's disease (AD). DESIGN: Responses of caregivers of patients with probable AD and responses of healthy control subjects on a standardized memory questionnaire were compared with objective measures of cognition (Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery) and with clinical estimates of activities of daily living, depression, and psychopathology (Consortium to Establish a Registry for Alzheimer's Disease [CERAD] clinical assessment battery) using the Self-report Memory Questionnaire. SETTING: A federally funded AD research center. SUBJECTS: The referred sample included 117 patients with probable AD, their informants, and 41 healthy control subjects age-matched to the patients. Patients and control subjects were between the ages of 58 and 85 years, had between 9 and 19 years of education, and were in good health. EXCLUSIONS: Patients who did not meet NINCDS-ADRDA criteria of probable AD. MAIN OUTCOME MEASURE: The optimal number of questionnaire items yielding the best combination of sensitivity and specificity. RESULTS: An abbreviated version of the scale, renamed the Short-Memory Questionnaire, had excellent specificity and sensitivity for identifying dementia. Positive and negative predictive values were 63.5% and near 100%, respectively. The Short-Memory Questionnaire showed good reliability, internal consistency, and external validity. Caregiver appraisals of memory deficits significantly correlated with objective measures of memory and also with generalized cognitive dysfunction. CONCLUSIONS: Caregivers of patients with AD are reliable informants of their relatives' deficits. The Short-Memory Questionnaire is an easily administered, informant-based scale that may be useful in clinical settings or epidemiologic studies to screen out persons with memory difficulties.     

Cross-form priming in normal aging and in mild dementia of the Alzheimer type

Twenty patients at early stages of Alzheimer's disease (AD), 20 elderly control subjects and 20 young subjects completed a cross-form priming task, followed by a free recall task. Results show that patients with mild AD display priming effects, and that these priming effects are strictly comparable to those obtained by elderly and young control subjects. Moreover, while the patients' performances are normal in the implicit part of the task, they are massively impaired in the explicit free recall task. These results don't support the hypothesis of a dissociation of performances between identification tasks and generation tasks in Alzheimer's disease, and show that conceptual priming can be observed at early stages of the disease, despite semantic memory impairments.     

Cognitive loss in dementia with Lewy bodies and Alzheimer disease

BACKGROUND: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). OBJECTIVE: To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. METHODS: We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])-Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. RESULTS: Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale-Revised were the best discriminant factors. CONCLUSIONS: The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.     

Discourse analysis of logical memory recall in normal aging and in dementia of the Alzheimer type.

This study examined the nature of errors in prose recall made in dementia compared with normal aging. Responses by 48 young adults, 47 nondemented older adults, and 70 people with very mild or mild Alzheimer's disease to the Logical Memory subtest of the Wechsler Memory Scale were examined in a propositional analysis. Compared with young adults, healthy older adults showed good immediate recall but deficits in retention over a delay. Demented individuals made errors of omission, not commission, at immediate recall. These errors probably reflect difficulty with attentional control rather than memory per se. In terms of clinical implications, veridical scoring of the Logical Memory subtest provides more sensitive detection of very mild dementia of the Alzheimer type than the current standard criteria for scoring. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amnestic mild cognitive impairment: Difference of memory profile in subjects who converted or did not convert to Alzheimer's disease.

Episodic long-term, short-term, and implicit memory were investigated in 79 elderly subjects who fulfilled criteria for the amnestic form of mild cognitive impairment (a-MCI; i.e., by having an idiopathic amnestic disorder with absence of impairment in cognitive areas other than memory and without confounding medical or psychiatric conditions) and who developed Alzheimer's disease (AD) after 2 years as well as in 111 subjects affected by a-MCI who did not develop dementia. Results document a memory profile in a-MCI subjects characterized by preserved short-term and implicit memory and extensive impairment of episodic long-term memory. In virtually all episodic memory indexes examined (learning, forgetting, recognition abilities), a-MCI subjects who converted to AD were more severely impaired than were subjects who did not become demented. This memory profile, which closely resembles that exhibited by amnestic patients with bilateral mesial-temporal lobe lesions, confirms a precocious phase in preclinical AD characterized by selective involvement of mesial-temporal areas and worsening of the memory impairment as atrophic changes progress in hippocampal structures. In this context of pervasive episodic memory impairment, tests assessing the free recall of verbal material following a delay interval demonstrated the greater sensitivity to memory deficits of a-MCI subjects who developed AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

IQ-memory discrepancies in normal and clinical samples.

The potential utility of IQ—Memory Index discrepancy scores derived from the Wechsler Adult Intelligence Scale—Revised (WAIS—R) and the Wechsler Memory Scale—Revised (WMS—R; D. Wechsler, 1987) was examined in a clinical sample, whose scores were then compared to those of subjects from the WMS—R standardization sample. The clinical sample included patients with diagnoses associated with memory deficits. Discrepancy scores between Full-Scale IQ and the Delayed Memory Index differentiated the groups, but material-specific discrepancies between IQ scores and immediate recall memory scores did not. The largest mean discrepancy and the greatest prevalence of scores beyond a criterion score of 15 were found in patients with presumed Alzheimer's disease. Issues related to limitations in the application of such discrepancy scores are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Working memory in mild Alzheimer's disease and early Parkinson's disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) impair working memory (WM). It is unclear, however, whether the deficits seen early in the course of these diseases are similar. To address this issue, the authors compared the performance of 22 patients with mild AD, 20 patients with early PD and without dementia, and 112 control participants on tests of inhibition, short-term memory, and 2 commonly administered tests of WM. The results suggest that although mild AD and early PD both impair WM, the deficits may be related to the interruption of different processes that contribute to WM performance. Early PD disrupted inhibitory processes, whereas mild AD did not. The WM deficits seen in patients with AD may be secondary to deficits in other cognitive capacities, including semantic memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory for gist and detail information in Alzheimer's disease and mild cognitive impairment.

Two experiments examined different forms of gist and detail memory in people with Alzheimer's disease (AD) and those with amnestic mild cognitive impairment (MCI). In Experiment 1, 14 AD, 14 MCI, and 22 control participants were assessed with the Deese-Roediger-McDermott paradigm. Results indicated that false recognition of nonstudied critical lures (gist memory) was diminished in the AD compared with the MCI and control groups; the two latter cohorts performed similarly. In Experiment 2, 14 AD, 20 MCI, and 26 control participants were tested on a text memory task. Results revealed that recall of both macropropositions (gist information) and micropropositions (detail information) decreased significantly in AD and in MCI as compared with control participants. This experiment also revealed that the impairment was comparable between gist and detail memory. In summary, the results were consistent across experiments in the AD but not in the MCI participants. The discrepancy in MCI participants might be explained by differences in the degree of sensitivity of the experimental procedures and/or by the differences in the cognitive processes these procedures assessed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Topographical organization of group II afferent input in the rat spinal cord

Recent data suggest that patients with Alzheimer's disease (AD) are able to show perceptual priming and, to some extent, conceptual priming for material which has preexisting representations in memory, and that normal elderly subjects are able to automatically activate pre-existing representations in both perceptual and conceptual priming tasks. An important question concerns the capacity of showing priming for materials without pre-existing representations in memory in normal and pathological aging. In order to address this issue, 20 patients with mild AD, 20 elderly controls and 20 young controls subjects were assessed with a paradigm of priming for new verbal associations. Neither the patients nor the normal elderly subjects demonstrated priming effects for new associations, while young subjects showed significant priming effects. These results suggest that the absence of priming for new verbal associations is attributable more to an effect of aging than to a specific effect of Alzheimer's disease.     

Feeling-of-knowing in fact retrieval: further evidence for preservation in early Alzheimer's disease

The ability to retrieve and monitor factual information varying in datedness (i.e., dated vs. contemporary) was examined in healthy older adults and patients in an early phase of Alzheimer's disease (AD). Subjects were given free recall and multiple-choice recognition tests of 48 general knowledge questions. For all questions not responded to in recall, subjects made feeling-of-knowing (FOK) judgments. Results indicated dementia-related deficits in both recall and recognition, although both groups showed better recall and recognition with the dated compared with the contemporary questions. Importantly, despite deficits in fact retrieval, the AD patients showed intact monitoring of stored knowledge, as indicated by equivalent FOK accuracy for both groups. In addition, FOK accuracy was similar for the dated and the contemporary information in both groups, suggesting independence between level of general knowledge and the ability to supervise information stored in memory.     

Repetition priming in normal aging and Alzheimer's disease: A review of findings and theories.

On repetition priming tasks, memory is measured indirectly as a change in performance due to recent experience. It is often functionally and neurally dissociated from performance on explicit memory tasks, which directly measure conscious recall or recognition of recent events. Repetition priming has therefore been extensively studied in normal aging and Alzheimer's disease, which feature mild to severe changes in explicit memory. Initial studies indicated that repetition priming was immune to the effects of aging and greatly reduced in Alzheimer's disease (AD). As more studies have been performed, however, these initial conclusions appear less clear than before and, in the case of AD, actually misleading. The purpose of this article is to provide a comprehensive review of this rapidly expanding literature, articulate the issues that are critical to interpreting the empirical results, and discuss what new conclusions are suggested by the overall pattern of findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Enhanced miotic response to topical dilute pilocarpine in patients with Alzheimer's disease

To determine whether miotic response to dilute (0.0625%, two drops) topical pilocarpine could be useful in detecting Alzheimer's disease (AD), we assessed the response in 14 AD patients and 10 control subjects. The miotic response to pilocarpine was significantly greater in AD patients than in control subjects (p < 0.001). In contrast, mydriatic response to the anticholinergic tropicamide (0.01%, one drop) failed to show a difference between the groups (p = 0.54). There was no significant correlation between the miotic and mydriatic responses in individuals. We conclude that dilute pilocarpine could be useful as a diagnostic tool in early AD.     

Episodic remembering in a population-based sample of nonagenarians: Does major depression exacerbate the memory deficits seen in Alzheimer's disease?

Population-based samples of normal old adults and people with major depression (MD), Alzheimer's disease (AD), and coexisting MD and AD (MD + AD) between 90 and 100 years of age were assessed in face recognition, word recall, and object recall. Results indicated a consistent pattern across tasks: no differences between the normal old and the MD participants or between the AD and MD + AD participants in any task, a clear performance decrement in the AD and MD + AD participants in all task variables reflecting long-term episodic memory, and no group differences in those variables reflecting short-term memory. These data suggest that depression in very old age may not exacerbate the episodic memory deficit that accompanies AD. Further, differences between normal old and MD participants in episodic memory tasks appear to be negligible among the oldest old. The general lack of effects of MD may be due to the fact that those symptoms of this disease that are most likely to affect memory functioning (e.g., loss of energy, concentration difficulties) are common in AD as well as in nondepressed people in the 10th decade of life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of aging and Alzheimer's disease on conceptual implicit and explicit memory.

The effects of aging and Alzheimer's disease (AD) on conceptual explicit and implicit memory were examined. Three groups of participants patients with AD; age-matched, older control participants; and younger control participants made deep (semantic) or shallow (nonsemantic) judgments about low-dominant category exemplars. Explicit memory was measured by category cued recall and implicit memory was measured by priming on a category-exemplar generation task. Younger participants had enhanced cued recall and priming following deep, relative to shallow, encoding; this indicated that both memory measures were conceptually driven. Aging reduced explicit, but not implicit, test performance, and it did not reduce conceptually driven processes for either test. In contrast, AD reduced explicit and implicit test performance, and it impaired conceptually driven memory processes for both tests. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Is There a Specific Executive Capacity for Dual Task Coordination? Evidence From Alzheimer's Disease.

Three experiments compared groups of Alzheimer's disease (AD) patients and healthy older and younger participants on visuospatial tracking and digit sequence recall, as single tasks and performed concurrently. In Experiment 1, tasks were performed concurrently with very low demand relative to span. Only the AD patients showed a dual task deficit. In Experiment 2, single task demand was manipulated on each task from below span to above span for each individual. All groups showed the same performance reductions with increasing demand. In Experiment 3, demand on 1 task was constant, whereas demand on the concurrent task was varied. AD patients showed a clear dual task deficit but were no more sensitive than control groups to varying demand. Results suggest an identifiable cognitive resource for dual task coordination within a multiple component working memory system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dysfunctional uterine bleeding

Alzheimer's disease (AD) is characterized by progressive dementia and distinct neuropathology at autopsy. In order to test the relationship between dementia severity and loss of brain volumes, we prospectively documented the neurological/medical health of 26 male and 26 female controls and AD cases, and evaluated a subset of controls and AD cases using the Mini Mental State Examination (MMSE). At autopsy, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria confirmed diagnoses in 33 AD cases and 19 controls, and using unbiased stereology we quantified total volumes of cortical gray matter, subcortical grey matter including white matter, and forebrain. For ages of death between 50 to 100 years, controls showed minor cortical atrophy in the absence of cognitive decline. Cortical atrophy in AD cases was 20 to 25% greater than that in controls; AD patients dying at older ages showed less severe cortical atrophy than those dying at younger ages. Across all AD cases there was a strong correlation between cognitive performance on the Mini Mental State Examination and cortical volume loss. These findings confirm fundamental differences in the temporal patterns of cortical volume loss in aging and AD, and support cortical degeneration as the primary basis for cognitive decline in AD.     

No increased incidence of Alzheimer's disease in elderly schizophrenics

There is currently controversy as to the morphological basis of cognitive impairment in elderly schizophrenics. In contrast to previous findings, recent studies have found no increased frequency of Alzheimer's disease (AD) pathology in elderly schizophrenics. We examined 99 consecutive autopsy cases of patients over the age of 55 years from a psychiatric hospital who met the DSM-III-R and ICD.10 criteria for schizophrenia (mean age 69.5 +/- 8.25 years; mean duration of illness 35.15 +/- 10.1 years), 56% showing moderate to severe dementia. All brains were blindly reviewed for evidence of AD using CERAD criteria and Braak staging of neuritic AD lesions. "Definite" AD (CERAD C, Braak stage V) was seen in 2 cases aged 56 and 67 years, respectively [2% of total or 1/68 (1.4%) of those over age 65]. "Probable" AD (CERAD B, Braak stages IV-V) were seen in 5 cases aged 71-89 years (mean 79 years; 5% of total or 7.3% of those over age 65), and 1 case each with multiple cerebral infarcts and with Parkinson's disease pathology. In addition, 2 females aged 82 and 89 years, respectively, revealed senile dementia with tangles (NIA, CERAD negative; Braak stage IV), 1 with hippocampal sclerosis. The total incidence of definite and probable AD in this cohort was 7.1% or 8.7% for those over age 65. This is in line with other recent studies showing that the frequency of AD in elderly schizophrenics may be equal or even less than in the general population. The reasons for this negative association and the basis of cognitive deficits in elderly schizophrenics--those with dementia usually showing significantly lower brain weight--await further elucidation.     

Influences of cognitive support on episodic remembering: Tracing the process of loss from normal aging to Alzheimer's disease.

Normal older adults, incident Alzheimer's disease (AD) patients, and prevalent AD patients were examined across a 3-year interval in episodic memory tasks that varied in terms of study time, organizability, and retrieval cues. There were marked overall preclinical deficits among the incident AD patients, although these patients were as effective as the normal older adults in utilizing more study time, organizability, and retrieval cues to improve memory at baseline. When these patients were diagnosed with AD at follow-up, they showed negligible gains from increased study time and organizability when memory was assessed with free recall, although they profited from the provision of retrieval cues. This pattern of results was also seen in the prevalent AD patients at both times of measurement. These results indicate that a general impairment of episodic memory may precede reductions in cognitive reserve capacity in the early development of AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)