Implicit memory for music in Alzheimer's disease

Short, unfamiliar melodies were presented to young and older adults and to Alzheimer's disease (AD) patients in an implicit and an explicit memory task. The explicit task was yes-no recognition, and the implicit task was pleasantness ratings, in which memory was shown by higher ratings for old versus new melodies (the mere exposure effect). Young adults showed retention of the melodies in both tasks. Older adults showed little explicit memory but did show the mere exposure effect. The AD patients showed neither. The authors considered and rejected several artifactual reasons for this null effect in the context of the many studies that have shown implicit memory among AD patients. As the previous studies have almost always used the visual modality for presentation, they speculate that auditory presentation, especially of nonverbal material, may be compromised in AD because of neural degeneration in auditory areas in the temporal lobes.     

Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer's disease

In Alzheimer's disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed.     

Changes in sleep theta rhythm are related to episodic memory impairment in early Alzheimer's disease

Impairments have been reported both in sleep structure and episodic memory in Alzheimer's disease [AD]. Our objective was to investigate the relationships between episodic memory deficits and electro-encephalography [EEG] abnormalities occurring during sleep in patients with early AD. Postlearning sleep was recorded in 14 patients with mild to moderate AD, and 14 healthy elderly controls after they performed an episodic memory task derived from the Grober and Buschke's procedure. For each sleep stage, the relative power and mean frequency in each band were analyzed. Relative to agematched controls, AD patients presented faster mean theta frequency in both REM sleep and slow wave sleep [SWS]. In AD patients, a correlative analysis revealed that faster theta frequency during SWS was associated with better delayed episodic recall. We assume that increased theta activity reflects changes in neuronal activity to maintain memory performance, indicating that compensatory mechanisms already described at the waking state could also be engaged during SWS.     

Mis-attribution errors in Alzheimer's disease: the illusory truth effect

Patients with mild Alzheimer's disease (AD) and age-matched controls were compared on a series of tasks designed to measure errors of mis-attribution, the act of attributing a memory or idea to an incorrect source. Mis-attribution was indexed through the illusory truth effect, the tendency for participants to judge previously encountered information to be true. Cognitive theories have suggested that the illusory truth effect reflects the mis-attribution of experimentally produced familiarity (a nonspecific sense that an item has been previously encountered) to the veracity of previously encountered information. Consistent with earlier suggestions that AD impairs both familiarity and recollection (specific memory for contextual details of the study episode), AD patients demonstrated significantly fewer mis-attribution errors under conditions in which the illusory truth effect is thought to rely on relative familiarity (uncued condition), but more mis-attribution errors under conditions thought to rely on relative amounts of contextual recollection (cued condition). These results help further specify the precise nature of memory impairments in AD.     

Inflammatory changes parallel the early stages of Alzheimer disease

Alzheimer disease (AD) is the most prominent cause of dementia in the elderly. To determine changes in the AD brain that may mediate the transition into dementia, the gene expression of approximately 10,000 full-length genes was compared in mild/moderate dementia cases to non-demented controls that exhibited high AD pathology. Including this latter group distinguishes this work from previous studies in that it allows analysis of early cognitive loss. Compared to non-demented high-pathology controls, the hippocampus of AD cases with mild/moderate dementia had increased gene expression of the inflammatory molecule major histocompatibility complex (MHC) II, as assessed with microarray analysis. MHC II protein levels were also increased and inversely correlated with cognitive ability. Interestingly, the mild/moderate AD dementia cases also exhibited decreased number of T cells in the hippocampus and the cortex compared to controls. In conclusion, transition into AD dementia correlates with increased MHC II⁺ microglia-mediated immunity and is paradoxically paralleled by a decrease in T cell number, suggesting immune dysfunction.     

Intact implicit habit learning in Alzheimer's disease

Habit learning refers to the incremental implicit learning of associations. Patients with Alzheimer's disease (AD) exhibit deficits in explicit memory and in conceptual implicit memory tasks that rely on the cortical areas damaged in AD. The authors tested patients with AD and controls on a probabilistic classification task in which participants implicitly acquire cue-outcome associations. Both groups showed evidence of learning across 50 trials, and performance did not differ significantly between the groups. In contrast, patients with AD exhibited a profound impairment in explicit memory for the testing episode. These results are consistent with the idea that habit learning relies on subcortical structures, including the basal ganglia, and is independent of the medial temporal and cortical areas damaged in AD.     

Daytime sleepiness in mild and moderate Alzheimer's disease and its relationship with cognitive impairment

The increased tendency to fall asleep during the daytime together with increased wakefulness during the night has been demonstrated in patients with advanced Alzheimer's disease (AD). The aim of this study was to assess daytime sleep propensity in a cohort of patients with mild/moderate AD and to correlate it with cognitive impairment. Twenty drug-free AD patients meeting the NINCDS-ADRDA criteria for probable AD were evaluated. According to their Clinical Dementia Rating scores, subjects were classified into mild (CDR1; n=11) and moderate (CDR2; n=9) dementia patients. A group of 12 healthy subjects was taken as controls. The subjects were evaluated by the multiple sleep latency test (MSLT) after their nocturnal sleep pattern had been assessed by a polysomnographic recording throughout the night before. Both groups of AD patients showed a higher level of daytime sleepiness, which was statistically significant for mean daytime sleep latency (MDSL) (controls versus CDR1 and versus CDR2, CDR1 versus CDR2) and for 10:00 and 12:00 hour naps (controls versus CDR1, controls versus CDR2). In the entire group of AD patients, MDSL was significantly related with MMSE, De Renzi's Token test, verbal fluency, verbal digit span, story recall, Raven's Progressive Matrices, Weigl test and Benton's three-dimensional test. These data indicate that an increased sleep propensity during daytime occurs also in patients with mild/moderate AD detected by objective neurophysiological techniques.     

Linear width of the medial temporal lobe can discriminate Alzheimer's disease from normal aging: the Sunnybrook dementia study

To discriminate Alzheimer's disease (AD) from healthy controls, the thinnest medial temporal lobe (tMTL) width on 3D-MRI was measured according to a newly developed method at the inter-collicular sulcus (ICS) level with scans aligned to the long axis of the hippocampus in 22 mild, 27 moderate probable AD patients and 41 healthy controls. For comparison, MTL width replicating the technique of Jobst et al. (jMTL) as well as hippocampal and parahippocampal volumes, were also measured. Using logistic regression taking into account age, sex, and education, tMTL width classified mild AD from controls with a sensitivity of 86%, specificity of 95% and accuracy of 92%. Similar values were obtained for moderate or total AD group versus controls. By comparison, jMTL width was only useful in distinguishing moderate AD from controls, and volumetric measures were equally sensitive in classifying mild and moderate AD in our sample. This quick, reliable, and standardized measurement of tMTL can be helpful in differentiating even mild AD from controls with reasonable accuracy.     

Implicit/explicit memory dissociation in Alzheimer's disease: the consequence of inappropriate processing?

Dual-process theories of recognition posit that perceptual fluency contributes to both familiarity-based explicit recognition and perceptual priming. However, the priming-without-recognition dissociation, as observed through the intact mere exposure effect and impaired recognition in patients with Alzheimer's disease (AD), might indicate that familiarity and perceptual priming are functionally distinct. This study investigated whether the AD patients' processing strategies at testing may explain this priming-without-recognition dissociation. First, we replicated the priming-without-recognition effect in 16 patients who exhibited intact exposure effects despite null recognition. Second, we showed that, under identical conditions, inducing a holistic processing strategy during recognition testing increased AD patients' recognition--performance was similar for AD patients and healthy control participants. Furthermore, prompting analytic processing during both priming and recognition tasks decreased AD patients' performance in both tasks. These findings suggest that the extent to which AD patients use perceptual fluency in priming and recognition tasks is contingent on their processing approach. The choice of processing strategy may depend on how difficult patients perceive the task to be.     

Humoral Immunity to Dietary Antigens in Atopic Dermatitis

Enzyme-linked immunosorbent assays (ELISA) employing a biotin-avidin amplification step are described for the quantification of human serum IgG antibodies to the dietary antigens ovalbumin (OA) and beta-lactoglobulin (BLG). The analytical quality of these assays was acceptable. Antibodies were measured in 16 patients with mild or moderate atopic dermatitis (AD), in 31 patients with a history of AD, and in closely matched controls. Levels of serum anti-OA antibodies did not differ in patients and controls, whereas anti-BLG antibodies tended to be higher in patients with mild or moderate AD than in controls (P less than 0.05).     

Clinical implications of quantitative electroencephalography and current source density in patients with Alzheimer's disease

This study examined whether quantitative electroencephalography (qEEG) and current source density (CSD) can be used to evaluate symptom severity in Alzheimer's disease (AD) patients. Thirty AD patients (13 mild and 17 moderate severity) and 30 normal control (NC) subjects were recruited. The Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet and the Global Deterioration Scale were measured. qEEG and CSD data were analyzed in five frequency bands: delta (1-3?Hz), theta (4-7?Hz), alpha (8-12?Hz), beta (13-25?Hz), and gamma (30-50?Hz). Compared with the NC subjects, the moderate AD patients had significantly increased theta and decreased beta power. Compared with the mild AD patients, the moderate AD patients had significantly decreased beta power. In the AD patients, the theta power was significantly correlated with a poor performance for global cognition; however, beta power was positively correlated with a good performance for global cognition, attention, memory, visuospatial function, and executive function. The CSD of the theta band in the superior temporal gyrus, transverse temporal gyrus, insula, postcentral gyrus, cuneus, and lingual gyrus was significantly different between NC subjects and moderate AD patients and between mild and moderate AD patients. The theta CSD of these regions was significantly correlated with a poor performance for global cognition, memory, visuospatial function, execution, and language. The results suggest that qEEG and the CSD of the theta and beta bands are useful biological markers in AD patients.     

Cognitive correlates of alterations in acetylcholinesterase in Alzheimer's disease

We recently reported findings of modest loss of cortical acetylcholinesterase (AChE) activity in patients with overall mild Alzheimer's disease (AD) using N-[11C]methyl-pi-peridin-4-yl propionate ([11C]PMP) AChE positron emission tomography (PET). To determine cognitive correlates of in vivo cortical AChE activity in patients with mild to moderate AD (n=15), and in normal controls (NC, n=12) using [11C]PMP AChE PET imaging. Mean cortical AChE activity in the AD subjects was mildly reduced (-11.1%) compared to the control subjects (P<0.05). Analysis of the cognitive data showed that mean cortical AChE activity was significantly associated with performance on a test of attention and working memory (WAIS-III Digit Span, R=0.46, P=0.01) but not with tests of delayed short or long-term memory functions. Similar findings were present when the analysis was limited to the temporal cortex. Cortical AChE activity is more robustly associated with functions of attention and working memory compared to performance on primary memory tests in AD.     

Numerosity Discrimination in Children With Down Syndrome

Six newly constructed cognitive scales with strong reliability for both Alzheimer's disease (AD) patients and healthy older adults were used to examine the pattern of deficits in AD. The performance of 31 patients with mild to moderate probable AD was impaired on all scales (p < .0005) relative to that of 31 age‐ and education‐matched normal controls. In the AD patients, the scales revealed profound, equivalent deficits in secondary verbal and nonverbal memory. Nonmemory deficits were most severe on a measure of executive function (mazes), which was followed by verbal reasoning, visual‐spatial reasoning and vocabulary. From these results, we hypothesized that primary dysfunction of frontal association areas may exceed that of parietal areas in AD. The relationship of this hypothesis to findings from previous studies of neu‐ropathological changes, cerebral glucose metabolism, and cognitive deficits in AD is discussed.     

Memory-related EEG power and coherence reductions in mild Alzheimer's disease.

OBJECTIVES: To examine memory-related EEG power and coherence over temporal and central recording sites in patients with early Alzheimer's disease (AD) and normal controls. METHOD: EEG was recorded from central (Fz, Cz and Pz) and temporal (T3 and T4) electrodes while ten very mild AD patients and ten controls performed a Sternberg-type memory scanning task with three levels of working memory load. Spectral power in delta (0-3 Hz), theta (3-5 Hz), lower alpha1 (5-7 Hz), lower alpha2 (7-9 Hz), upper alpha (9-11 Hz) and beta (15-30 Hz) was averaged for temporal and central electrodes. Coherence was averaged between central electrodes, between central and right temporal electrodes and between central and left temporal electrodes. RESULTS: While behavioral performance of very mild AD patients did not differ significantly from that of normal controls, findings suggest that normal controls but not AD patients respond to memory demands by increasing upper alpha power over temporal cortex. When compared with normal controls, AD patients had reduced upper alpha coherence between central and right temporal cortex. DISCUSSION: Results are consistent with previous research on the role of upper alpha in semantic memory and suggest that very mild AD may inhibit selective synchronization of upper alpha in temporal lobes. Reduced coherence between central and temporal cortex is discussed in light of a neurological model of AD that hypothesizes reduced electrocortical efficiency and a breakdown of neural network communication to temporal lobes possibly resulting from temporal lobe atrophy.     

Hippocampal Proton MR Spectroscopy in Early Alzheimer��s Disease and Mild Cognitive Impairment

Proton magnetic resonance spectroscopy ((1)H-MRS) studies have previously reported reduced brain N-acetyl aspartate (NAA) and increased myo-inositol (mI) in people with established Alzheimer's disease (AD). The earliest structure affected by AD is the hippocampus but relatively few studies have examined its neuronal integrity by MRS in AD and fewer still in people with amnestic mild cognitive impairment (MCI). We measured the hippocampal concentration of NAA, mI, choline (Cho) and creatine?+?phosphocreatine (Cr?+?PCr) in 39 patients with AD, 21 subjects with MCI and 38 age matched healthy elderly controls. Patients with AD had a significantly lower hippocampal [NAA] than controls, with subjects with MCI intermediate between the other two groups. [NAA] was positively correlated with memory in the impaired groups. Using mean hippocampal [NAA] and [Cr?+?PCr] we correctly classified 72% of people with AD, and 75% of controls. Reductions in [NAA] can be detected in the hippocampi of subjects with MCI and hippocampal [NAA] and [Cr?+?PCr] can distinguish between mild AD and normal elderly controls.     

阿尔茨海默病患者的汉字阅读能力研究

目的:研究汉语文化背景下的阿尔茨海默病患者的阅读能力和失读的特点。方法:正常老人、轻、中、重度AD各20名,性别、年龄和教育程度匹配。4组受试简明精神状态量表(MMSE)总分分别为27.7±2.2分、21.2±2.2分、15.2±2.3分和6.9±2.6分。汉字阅读包括22个记号字、17个音符字和17个义符字。结果:不管是记号字、音符字还是义符字,在正常老人组、轻度AD组和中度AD组之间两两比较没有显著差异(P>0.05),音符字和义符字在中度和重度AD组之间比较有显著差异(P<0.01)。“视觉性错读”在四组之间没有显著差异(P>0.05),表层失读出现在AD早期,并在AD晚期明显加重,好发于声符与其本字的发音不一致的义符字,不能用左侧忽视来解释。深层失读仅出现在AD晚期。组词现象是汉字深层失读的主要类型。结论:可以通过汉字阅读能力的评估判断早期痴呆被试的病前智力。汉字失读的类型与西方语言不同。     

Preliminary data on the effect of culture on the assessment of Alzheimer's disease-related verbal memory impairment with the International Shopping List Test

The International Shopping List Test (ISLT) is a measure of verbal learning and memory, developed specifically for use in people from different cultural and linguistic backgrounds. In this report, we describe two studies that examined the ISLT's ability to detect memory impairment and memory decline in patients with mild Alzheimer's disease (AD) from a range of cultural and linguistic backgrounds. In Study 1, the performance of Australian-English-speaking adults with mild AD was compared with that of native Australian-English- and Korean-speaking patients with mild AD. Compared with controls, patients with AD from both language groups showed large but equivalent impairments in total recall, delayed recall, rate of learning, and primacy and retention-weighted recall (RWR) measures on the ISLT. In Study 2, the rate of deterioration in verbal memory over 1 year was examined in groups of native Canadian-English, French, and Korean speakers with mild AD using the total recall, delayed recall, and RWR measures. Rates of change on all three measures were equivalent across the language groups, although the magnitude of deterioration was most pronounced for the total recall and RWR measures. Taken together, these results suggest that the ISLT is valid and reliable for the assessment of verbal learning and memory impairment and decline in patients with mild AD from diverse language groups.     

Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer's disease

In Alzheimer's disease (AD), brain lesions are marked by severe neuronal loss and retinal degeneration was previously mentioned in affected patients. Mild cognitive impairment (MCI) is a clinical syndrome that could be an early phase of AD. In this study, using optical coherence tomography (OCT), the retinal nerve fiber layer (RNFL) thickness was assessed in patients with mild AD, moderate to severe AD, amnestic MCI and control subjects. The results show that RNFL thickness is statistically reduced in patients with MCI, mild AD or moderate to severe AD compared to controls. In addition, no statistical difference was found between the results in MCI patients and mild AD patients. The RNFL seems to be involved early during the course of amnestic MCI and OCT tests could be carried out in patients with cognitive troubles.     

Executive function deficits in early Alzheimer's disease and their relations with episodic memory.

Previous research suggests that patients with Alzheimer's disease (AD) are impaired on executive function early in the course of disease, but negative findings were reported. To evaluate the performance on executive tasks in early AD and to determine the involvement of memory on the outcome of executive tasks. Thirty-six AD patients were divided into two subgroups on the basis of the MMSE: very mild and mild. The comparison with 17 normal controls shows that very mild AD patients had deficits on visuospatial short-term memory, episodic memory, flexibility and self-monitoring abilities, concept formation and reasoning. The mild AD patients showed additional deficits on the Similarities test. Episodic memory and executive deficits occur in the very early stage of AD and precede impairment in constructional praxis, language and sustained attention. With the progression of the disease, additional deficit is observed in abstract thinking. In mild AD, memory failure is also related to executive impairment.     

Perspective taking to assess self-personality: what's modified in Alzheimer's disease?

Personality changes are frequently described by caregivers of patients with Alzheimer's disease, while they are less often reported by the patients. This relative anosognosia of Alzheimer disease (AD) patients for personality changes might be related to impaired self-judgment and to decreased ability to understand their caregiver's perspective. To investigate this issue, we explored the cerebral correlates of self-assessment and perspective taking in patients with mild AD, elderly and young volunteers. All subjects assessed relevance of personality traits adjectives for self and a relative, taking either their own or their relative's perspective, during a functional imaging experiment. The comparison of subject's and relative's answers provided congruency scores used to assess self-judgment and perspective taking performance. The self-judgment "accuracy" score was diminished in AD, and when patients assessed adjectives for self-relevance, they predominantly activated bilateral intraparietal sulci (IPS). Previous studies associated IPS activation with familiarity judgment, which AD patients would use more than recollection when retrieving information to assess self-personality. When taking a third-person perspective, patients activated prefrontal regions (similarly to young volunteers), while elderly controls recruited visual associative areas (also activated by young volunteers). This suggests that mild AD patients relied more on reasoning processes than on visual imagery of autobiographical memories to take their relative's perspective. This strategy may help AD patients to cope with episodic memory impairment even if it does not prevent them from making some mind-reading errors.