Very Early Decline in Recognition Memory for Odors in Alzheimer’s Disease

When in the progression of Alzheimer’s disease (AD) a decline in detection sensitivity and recognition memory for odors begins, and whether a fast progression in dementia is related to a fast loss in odor sensitivity, was determined by studying 78 patients with probable AD, categorized as very mild, mild, or moderate in degree of dementia, and 78 controls. Taste and vision were studied for comparison. Whereas the earliest decline in odor sensitivity and visual memory was found in mild patients, a decline in odor memory was found in the very mild patients. Similar taste thresholds in the four groups suggest that the poor odor detectability in AD was not related to task demands in threshold testing. A fast progression in dementia was also found to be related to a fast loss in odor sensitivity. The findings imply that memory-based olfactory tests may contribute to early diagnosis of AD.     

Alzheimer's Disease Patients' Cognitive Status and Course Years Prior to Symptom Recognition

This is a prospective examination of the cognitive performance and cognitive course of persons in an asymptomatic “preclinical” phase who eventually developed Alzheimer's disease (AD). We compared performances on the Mayo Cognitive Factor Scales (MCFS) of 20 persons in a neurologically normal cohort who subsequently developed AD to the performances of 60 persons who remained free of dementia symptoms. For the AD patients, exams occurred prior to the appearance of dementia symptoms (an average of 4.2 and 1.5 years prior to symptom onset). Results reveal strong group differences on learning and retention, with eventual AD patients scoring lower than controls years prior to reporting symptoms of the disease. There was no significant interaction effect (group × testing session) for memory retention, suggesting that memory decline in this preclinical period may be too slow to be a useful indicator of future AD. A significant interaction (but no group effect) was seen for verbal comprehension.     

Cognitive Functioning in Aging and Dementia: The Kungsholmen Project

The Kungsholmen Project (KP) is a community-based longitudinal study of aging and dementia targeting the 75+ population. In this article, we review empirical studies with a cognitive focus from the KP. The main findings indicate that (a) there is an age-related decline for some cognitive domains (e.g., episodic memory, verbal fluency, visuoconstructive skill, psychomotor speed), but not for others (e.g., primary memory, visuoperceptive skill, motor-hand coordination), (b) multiple individual-difference variables within demographic (e.g., sex, education) life-style (e.g., activity levels), genetic (e.g., apolipoprotein E genotype), and health-related (e.g., vitamin B deficiency, depression, diabetes) domains are related to late-life cognitive functioning, (c) a potential for improving cognitive performance – a reserve capacity – is present also among very old adults, (d) the 2 most common dementia diseases, Alzheimer’s disease (AD) and vascular dementia (VaD), affect cognition in a strikingly similar manner, (e) the role of individual-difference variables in cognitive functioning is markedly reduced in dementia – the pathogenesis itself may overshadow the influence of other variables, and (f) there is a long preclinical period in dementia during which cognitive deficits are detectable. As is true with the other projects represented in this issue, the KP portrays a rather diversified picture of cognitive aging, although systematic patterns are evident with regard to the variability of late-life cognitive functioning.     

Alzheimer's disease patients' cognitive status and course years prior to symptom recognition

This is a prospective examination of the cognitive performance and cognitive course of persons in an asymptomatic "preclinical" phase who eventually developed Alzheimer's disease (AD). We compared performances on the Mayo Cognitive Factor Scales (MCFS) of 20 persons in a neurologically normal cohort who subsequently developed AD to the performances of 60 persons who remained free of dementia symptoms. For the AD patients, exams occurred prior to the appearance of dementia symptoms (an average of 4.2 and 1.5 years prior to symptom onset). Results reveal strong group differences on learning and retention, with eventual AD patients scoring lower than controls years prior to reporting symptoms of the disease. There was no significant interaction effect (group x testing session) for memory retention, suggesting that memory decline in this preclinical period may be too slow to be a useful indicator of future AD. A significant interaction (but no group effect) was seen for verbal comprehension.     

Lifespan brain activity, β-amyloid, and Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of progressive cognitive decline and dementia in adults. While the amyloid cascade hypothesis of AD posits an initiating role for the β-amyloid (Aβ) protein, there is limited understanding of why Aβ is deposited. A growing body of evidence based on in vitro, animal studies and human imaging work suggests that synaptic activity increases Aβ, which is deposited preferentially in multimodal brain regions that show continuous levels of heightened activation and plasticity across the lifespan. Imaging studies of people with genetic predispositions to AD are consistent with these findings, suggesting a mechanism whereby neural efficiency or cognitive reserve may diminish Aβ deposition. The aggregated findings unify observations from cellular and molecular studies with human cognitive neuroscience to reveal potential mechanisms of AD development.     

The diagnostic role of serum inflammatory and soluble proteins on dementia subtypes: correlation with cognitive and functional decline

In the past years, the possible involvement of inflammation in the pathogenesis of dementia has been the subject of several investigations. However there are restricted data about the profile of the inflammatory and soluble proteins in well evaluated Alzheimer's disease (AD), vascular dementia (VD), mild cognitive impairment (MCI) and healthy controls. There are also no reliable data regarding the relationship between the overlapping protein levels and cognitive or functional decline. We measured levels of IL-1beta, IL-2, IL-6, IL-18, TNF-alpha, beta-Amlyloid 1-40 and alpha1-antichymotrypsin levels in plasma in groups of total 82 subjects with AD, MCI, VD and controls using enzyme-linked immunosorbent assay (ELISA) method. Our study samples showed high levels of proinflammatory cytokine levels (especially IL-18) in all patient groups but only high levels of alpha1-antichymotrypsine in VD patients compared to controls. There is no significant correlation between the laboratory and clinical variables except for a link between IL-1beta and NPI scores of AD. In conclusion, this study yielded evidence of some shared mechanisms underlying AD and VD and thus motivates further studies of inflammatory markers in various types of dementia and MCI.     

The Differential Effects of Alzheimer's Disease and Lewy Body Pathology on Cognitive Performance: a Meta-analysis

Differential diagnosis of Alzheimer’s disease (AD) from normal aging and other dementia etiologies is imperative for disease specific treatment options and long-term care planning. Neuropathological confirmation is the gold standard for neurodegenerative disease diagnosis, yet most published studies examining the use of neuropsychological tests in the differential diagnosis of dementia rely upon clinical diagnostic outcomes. The present study undertook a meta-analytic review of the literature to identify cognitive tests and domains that allow for the differentiation of individuals with AD pathology from individuals with dementia with Lewy Bodies (DLB) pathology and pathology-free individuals. A comprehensive literature search yielded 14 studies that met the inclusion criteria for the present meta-analysis. Six studies comprised 222 decedents with AD compared to 433 normal controls, and eight studies comprised 431 cases of AD compared to 155 decedents with DLB. Results revealed that the effect of having neuropathologically confirmed AD versus DLB lowered performance in the memory domain, and having DLB decreased performance in the visuospatial domain. No single test differed significantly across the AD and DLB groups. For the AD and pathology free comparison, results indicated that that AD was associated with poorer performance on the memory and language domains. With respect to specific cognitive tests, AD produced lower scores on list learning tests, category fluency, and the Digit Symbol substitution test. The limited number of studies meeting inclusion criteria warrants formulation of guidelines for reporting in clinico-pathological studies; suggested guidelines are provided.     

Longitudinal change in language production: effects of aging and dementia on grammatical complexity and propositional content.

Mixed modeling was used to examine longitudinal changes in linguistic ability in healthy older adults and older adults with dementia. Language samples, vocabulary scores, and digit span scores were collected annually from healthy older adults and semiannually from older adults with dementia. The language samples were scored for grammatical complexity and propositional content. For the healthy group, age-related declines in grammatical complexity and propositional content were observed. The declines were most rapid in the mid 70s. For the group with dementia, grammatical complexity and propositional content also declined over time, regardless of age. Rates of decline were uniform across individuals. These analyses reveal how both grammatical complexity and propositional content are related to late-life changes in cognition in healthy older adults aswell as those with dementia. Alzheimer's disease accelerates this decline, regardless of age.     

Monitoring the Changing Status of Semantic Memory in Alzheimer's Disease: An Evaluation of Several Process Measures

The deficits in generating correct words on verbal fluency tasks exhibited by patients with Alzheimer's disease (AD) are accompanied by fewer switching responses, smaller phonemic and semantic cluster sizes, and greater than normal percentages of errors and category labels. On category fluency tasks, patients generate a greater proportion of words that are prototypical of their semantic class. To determine whether any of these supplementary measures of verbal fluency performance might be useful in revealing processes involved in the decline of semantic memory in AD, we studied 219 patients with AD and 115 elderly control participants longitudinally. Previously reported group differences between patients and controls were replicated, but changes in average cluster size, error rates, and prototypicality were not related to changes in overall severity of dementia and test-retest stability was only modest. The change in the percentage of labels generated on the Supermarket task was related to changes in dementia severity, but test-retest stability on this measure was quite low. All of these process measures appear to reflect only the current status of the patient's attention to the task and access to semantic knowledge, but they do not forecast future performance. The numbers of switching responses on the fluency tasks were sensitive to differences between clinically deteriorated and clinically stable patients and showed fairly high test-retest stability. However, the number of switching responses is so highly correlated with the number of correct words that it contributes little to the understanding of the processes involved in the progressive decline in performance on fluency tasks by patients with AD.     

Influence of education on the pattern of cognitive deterioration in AD patients: the cognitive reserve hypothesis

The cognitive reserve hypothesis proposes that a high educational level could delay the clinical expression of Alzheimer's disease (AD) although neuropathologic changes develop in the brain. Therefore, some studies have reported that when the clinical signs of the disease emerge, high-educated patients may decline more rapidly than low-educated patients because the neuropathology is more advanced. However, these studies have only investigated the decline of global cognition or an isolated cognitive process. To study the differential deterioration pattern of several cognitive processes according to education, the performance of 20 AD patients with a high educational level and a low educational level were compared with the performance of 20 control subjects on a neuropsychological battery. The results showed that cognitive deterioration of AD patients is different according to education, although the global performance was similar in AD patients. The high-educated patients exhibited greater impairment of abstract thinking whereas the low-educated patients showed greater impairment of memory and attentional function. This confirms that some cognitive processes, such as abstract thinking, decline more rapidly in high-educated patients whereas others seem to evolve more slowly if compared to low-educated patients. In this latter case, high-educated patients may still benefit from cognitive reserve after the diagnosis of the dementia.     

The generalizability of training gains in dementia: effects of an imagery-based mnemonic on face-name retention duration

The generalizability of the results from a case study on the effects of an imagery mnemonic on face-name recall in dementia was examined (Hill, Evankovich, Sheikh, & Yesavage, 1987). Seven patients with Alzheimer's disease (AD) and 1 patient with multi-infarct dementia (MID) were trained by using the method devised by Hill et al. Application of the mnemonic increased the time during which face-name associations could be held in memory for 1 AD patient, and this improvement was maintained in a 1-month follow-up assessment. However, no training gains were observed for the remaining 7 patients, thus questioning the generalizability of this method in enhancing memory in dementia.     

Category and Attribute Knowledge Deterioration in Alzheimer's Disease

A prevalent theory regarding the deterioration of semantic memory in Alzheimer's disease is that it is a bottom-up process. If this is true, performance on tests of attribute knowledge should decline more rapidly than performance on tests of categorical knowledge as dementia severity increases. In the present study, a convincing pattern of findings to either support or reject the theory failed to emerge. This raised questions regarding the ability to separate attribute and categorical knowledge, and whether one can be tested without influence of the other. Questions also were raised regarding the additional cognitive processes needed to complete tasks of semantic memory.     

Perceptual organization based upon spatial relationships in Alzheimer's disease

Alzheimer's disease (AD) is often accompanied by impaired object recognition, thereby reducing the ability to recognize common objects and familiar faces. Impaired recognition may stem from decreased efficacy in integrating visual information. Studies of perceptual abnormalities in AD indicate an impairment in organizing elements of the visual scene, thereby confusing components of individual forms. This type of impairment is consistent with the characteristics of neural loss, which impact cortical integration. To examine the extent to which perceptual organization is impaired in AD, psychophysical measurements were made of visual perceptual grouping based upon spatial relationships in a group of AD patients and demographically matched elderly control subjects. A comparison was also made between young and elderly control subjects to evaluate the effects of aging on these capacities. Deficits in perceptual organization were found for a subgroup of AD patients, which corresponded to impairment on facial recognition. A less profound functional decline was found for the elderly control group. The degree of impairment for AD subjects did not correlate to level of dementia, but instead appears to be idiosyncratic to individual patients. These results are consistent with impaired integrative function in AD, the degree of which reflects individual differences in the regional distribution of neuropathological changes.     

Pattern of language impairment is different in Alzheimer's disease and multi-infarct dementia.

Language impairment was assessed in 33 patients with Alzheimer's disease (AD), in 52 patients with multi-infarct dementia (MID), and in 86 elderly community residents. The investigation included the D-Test Battery based on the Luria's Neuropsychological Investigation for all subjects. An extended battery of Luria's language items was used for 30 demented patients (11 AD and 19 MID patients) and 86 controls. The changes in language functions in normal subjects could be clearly differentiated from those seen in patients with mild dementia. The patients with different degrees of dementia differed also significantly from each other in regard to language impairment. Moreover, patients with AD and MID appeared to have different patterns of language impairment although the severity of dementia and the levels of orientation, mnestic, and conceptual functions were equal. AD was associated especially with a defect in understanding of grammatical structures and MID with disorders in recognition of words, naming, and repetition. The differential diagnostic capacity of 23 selected language items proved to be 97% between AD, MID, and control subjects. The results indicate that the examination of language functions is valuable in the differential diagnosis of dementia.     

Exercise Training for Persons with Alzheimer's Disease and Caregivers: A Review of Dyadic Exercise Interventions

Alzheimer's disease (AD) is the most common form of dementia and the prevalence will increase dramatically in the next decades. Although exercise has shown benefits for people with dementia due to AD as well as their caregivers, the impact of a dyadic exercise intervention including both groups as study participants remains to be determined. The authors review the current clinical evidence for dyadic exercise interventions, which are exercise regimens applied to both the person with dementia and the caregiver. A total of 4 controlled trials were reviewed. This review shows that dyadic exercise interventions are feasible and may produce a positive effect on functional independence and caregiver burden. However, there was insufficient evidence to support a benefit of dyadic exercise intervention on cognitive performance and on behavioral and neuropsychiatric symptoms in participants with dementia due to AD. A dyadic exercise intervention improves functional independence and caregiver burden. However, there is a need for well-designed randomized controlled clinical trials to confirm these benefits and to investigate several important points such as the effects of a dyadic exercise intervention on cognitive and noncognitive outcomes of AD, the optimal intensity of exercise training, and the cost effectiveness of such a program.     

Gait and risk of falls associated with frontal cognitive functions at different stages of Alzheimer's disease

ABSTRACT The decline in frontal cognitive functions contributes to alterations of gait and increases the risk of falls in patients with dementia, a category which included Alzheimer's disease (AD). The objective of the present study was to compare the gait parameters and the risk of falls among patients at different stages of AD, and to relate these variables with cognitive functions. This is a cross-sectional study with 23 patients with mild and moderate AD. The Clinical Dementia Rating was used to classify the dementia severity. The kinematic parameters of gait (cadence, stride length, and stride speed) were analyzed under two conditions: (a) single task (free gait) and (b) dual task (walking and counting down). The risk of falls was evaluated using the Timed Up-and-Go test. The frontal cognitive functions were evaluated using the Frontal Assessment Battery (FAB), the Clock Drawing Test (CDT) and the Symbol Search Subtest. The patients who were at the moderate stage suffered reduced performance in their stride length and stride speed in the single task and had made more counting errors in the dual task and still had a higher fall risk. Both the mild and the moderate patients exhibited significant decreases in stride length, stride speed and cadence in the dual task. Was detected a significant correlation between CDT, FAB, and stride speed in the dual task condition. We also found a significant correlation between subtest Similarities, FAB and cadence in the dual task condition. The dual task produced changes in the kinematic parameters of gait for the mild and moderate AD patients and the gait alterations are related to frontal cognitive functions, particularly executive functions.     

Functional decline in the early stages of Alzheimer's disease

At present most reports of functional decline in patients with Alzheimer's Disease (AD) are anecdotal, and few studies have objectively documented the course of the disease. This is a report of a 2-year follow-up of 15 AD patients characterized by mild functional impairment, and 22 age-, sex-, and education-matched control subjects. In a previous cross-sectional study of these 37 subjects and 16 AD patients with moderate functional impairment, we found that measures of memory and attention deficits accounted for much of the impairment observed in functional competence. The current longitudinal study found that these same initial assessments could be used to predict functional decline in the 15 mildly impaired patients. These patients were observed to decline to levels similar to those of the 16 moderate patients. In contrast, the control subjects exhibited little decline during the same period. These results both affirm that it is possible to diagnose AD in its mild form and demonstrate the validity of the initial diagnosis.     

Age-associated memory impairment: Definition and psychometric characteristics

Abstract

The basic definition of Age-Associated Memory Impairment (AAMI) is considered, with a particular emphasis on the psychometric features of AAMI. Empirical data are presented concerning the prevalence of AAMI and demonstrating the importance of quantifying both objective age-related decline in secondary memory as well as subjective report of decline relative to young adult years. Failure to include both of these features leads to overestimation of the prevalence of AAMI. Differences in memory test performance and subjective memory ratings are presented for subjects with AAMI and Alzheimer-type dementia relative to age and education matched elderly controls. Finally, modifications to the original AAMI psychometric criteria are suggested. More precise psychometric criteria are provided for differentiation of AAMI, dementia and amnestic disorder.     

Neuropsychological predictors of conversion to probable Alzheimer disease in elderly with mild cognitive impairment

In the field of neuropsychology, it is essential to determine which neuropsychological tests predict Alzheimer's disease (AD) in people with mild cognitive impairment (MCI) and which cut‐off points should be used to identify people at greater risk for converting to dementia. The aim of the present study was to analyse the predictive value of the cognitive tests included in a neuropsychological battery for conversion to AD among MCI participants and to analyse the influence of some sociodemographic variables – sex, age, schooling – and others, such as follow‐up time and emotional state. A total of 105 participants were assessed with a neuropsychological battery at baseline and during a 3‐year follow‐up period. For the present study, the data were analysed at baseline. During the follow‐up period, 24 participants (22.85%) converted to dementia (2.79 ± 1.14 years) and 81 (77.14%) remained as MCI. The logistic regression analysis determined that the long delay cued recall and the performance time of the Rey figure test were the best predictive tests of conversion to dementia after an MCI diagnosis. Concerning the sociodemographic factors, sex had the highest predictive power. The results reveal the relevance of the neuropsychological data obtained in the first assessment. Specifically, the data obtained in the episodic verbal memory tests and tests that assess visuospatial and executive components may help to identify people with MCI who may develop AD in an interval not longer than 4 years, with the masculine gender being an added risk factor.     

Appraisal of Memory Functioning and Memory Performance in Healthy Ageing and Early-Stage Alzheimer's Disease

ABSTRACT

Background/Aims: To compare memory evaluations in healthy older people and people with Alzheimer's disease (AD) and present standardised individual and dyadic methods for classifying degree of memory awareness in the participants with dementia. Methods: Cross-sectional study evaluating awareness of memory functioning and performance and providing normative data for healthy individuals and couples, together with comparison data from people with AD. Results: As a group, older people are reasonably accurate raters of their own memory functioning and performance, although considerable individual differences can be observed, and control dyads show good comparative accuracy. Comparing normative data from the control group to data from participants with AD confirms that significant overestimation is a frequent feature among people with dementia, with approximately two-thirds showing this pattern, although significant under-estimation is also reliably observed in a small proportion of people with dementia. Different types of measure elicit different profiles of memory awareness in participants with dementia. Conclusion: Normative data from older individuals and couples provides useful percentile-based indices for determining level of memory awareness in people with dementia.