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Background and Objectives Sleep disorders often predict or co-occur with cognitive decline. Yet, little is known about how the relationship unfolds among older adults at risk for cognitive decline. To examine the associations of sleep disorders with cognitive decline in older adults with unimpaired cognition or impaired cognition (mild cognitive impairment and dementia). Research Design and Methods A total of 5,822 participants (M age = 70) of the National Alzheimer's Coordinating Center database with unimpaired or impaired cognition were followed for 3 subsequent waves. Four types of clinician-diagnosed sleep disorders were reported: sleep apnea, hyposomnia/insomnia, REM sleep behavior disorder, or "other." Cognition over time was measured by the Montreal Cognitive Assessment (MoCA) or an estimate of general cognitive ability (GCA) derived from scores based on 12 neuropsychological tests. Growth curve models were estimated adjusting for covariates. Results In participants with impaired cognition, baseline sleep apnea was related to better baseline MoCA performance (b  = 0.65, 95% confidence interval [95% CI] = [0.07, 1.23]) and less decline in GCA over time (b  = 0.06, 95% CI = [0.001, 0.12]). Baseline insomnia was related to better baseline MoCA (b  = 1.54, 95% CI = [0.88, 2.21]) and less decline in MoCA over time (b  = 0.56, 95% CI = [0.20, 0.92]). Furthermore, having more sleep disorders (across the 4 types) at baseline predicted better baseline MoCA and GCA, and less decline in MoCA and GCA over time. These results were only found in those with impaired cognition and generally consistent when using self-reported symptoms of sleep apnea or insomnia. Discussion and Implications Participants with sleep disorder diagnoses may have better access to healthcare, which may help maintain cognition through improved sleep. [ABSTRACT FROM AUTHOR]

Background To examine cross-sectional differences and longitudinal changes in cognitive performance based on the presence of mild behavioral impairment (MBI) among older adults who are cognitively healthy or have mild cognitive impairment (MCI). Methods Secondary data analysis of participants (n = 17 291) who were cognitively healthy (n = 11 771) or diagnosed with MCI (n = 5 520) from the National Alzheimer's Coordinating Center database. Overall, 24.7% of the sample met the criteria for MBI. Cognition was examined through a neuropsychological battery that assessed attention, episodic memory, executive function, language, visuospatial ability, and processing speed. Results Older adults with MBI, regardless of whether they were cognitively healthy or diagnosed with MCI, performed significantly worse at baseline on tasks for attention, episodic memory, executive function, language, and processing speed and exhibited greater longitudinal declines on tasks of attention, episodic memory, language, and processing speed. Cognitively healthy older adults with MBI performed significantly worse than those who were cognitively healthy without MBI on tasks of visuospatial ability at baseline and on tasks of processing speed across time. Older adults with MCI and MBI performed significantly worse than those with only MCI on executive function at baseline and visuospatial ability and processing speed tasks across time. Conclusions This study found evidence that MBI is related to poorer cognitive performance cross-sectionally and longitudinally. Additionally, those with MBI and MCI performed worse across multiple tasks of cognition both cross-sectionally and across time. These results provide support for MBI being uniquely associated with different aspects of cognition. [ABSTRACT FROM AUTHOR]

Innovative memory paradigms have been introduced to capture subtle memory changes in early Alzheimer's disease (AD). We aimed to examine the associations between different indexes of the challenging Memory Binding Test (MBT) and hippocampal volume (HV) in a sample of individuals with subjective cognitive decline (SCD; n = 50), amnestic mild cognitive impairment (aMCI) due to AD (n = 31), and cognitively normal (CN) older adults (n = 29) recruited from the Czech Brain Aging Study, in contrast to traditional verbal memory tests. Both MBT free and cued recall scores in immediate and delayed recall conditions were associated with lower HV in both SCD and aMCI due to AD, whereas in traditional verbal memory tests only delayed recall scores were associated with lower HV. In SCD, the associations with lower HV in the immediate recall covered specific cued recall indexes only. In conclusion, the MBT is a promising test for detecting subtle hippocampal-associated memory decline during the predementia continuum. [ABSTRACT FROM AUTHOR]

Background: Memory tests using controlled encoding and cued recall paradigm (CECR) have been shown to identify prodromal Alzheimer's disease (AD), but information about the effectiveness of CECR compared to other memory tests in predicting clinical progression is missing.Objective: The aim was to examine the predictive ability of a memory test based on the CECR paradigm in comparison to other memory/non-memory tests for conversion to dementia in patients with amnestic mild cognitive impairment (aMCI).Methods: 270 aMCI patients from the clinical-based Czech Brain Aging Study underwent a comprehensive neuropsychological assessment including the Enhanced Cued Recall test (ECR), a memory test with CECR, two verbal memory tests without controlled encoding: the Auditory Verbal Learning Test (AVLT) and Logical memory test (LM), a visuospatial memory test: the Rey-Osterrieth Complex Figure test, and cognitive testing based on the Uniform Data Set battery. The patients were followed prospectively. Conversion to dementia as a function of cognitive performance was examined using Cox proportional hazard models.Results: 144 (53%) patients converted to dementia. Most converters (89%) developed dementia due to AD or mixed (AD and vascular) dementia. Comparing the four memory tests, the delayed recall scores on AVLT and LM best predicted conversion to dementia. Adjusted hazard ratios (HR) of immediate recall scores on ECR, AVLT, and LM were similar to the HR of categorical verbal fluency.Conclusion: Using the CECR memory paradigm in assessment of aMCI patients has no superiority over verbal and non-verbal memory tests without cued recall in predicting conversion to dementia. [ABSTRACT FROM AUTHOR]

Background: There is currently no therapeutic that can stop or reverse the progressive memory impairment of Alzheimer's disease (AD). However, we recently published that 2 months of daily, in-home transcranial electromagnetic treatment (TEMT) reversed the cognitive impairment in eight mild/moderate AD subjects. These cognitive enhancements were accompanied by predicted changes in AD markers within both the blood and cerebrospinal fluid (CSF). Methods: In view of these encouraging findings, the initial clinical study was extended twice to encompass a period of 2½ years. The present study reports on the resulting long-term safety, cognitive assessments, and AD marker evaluations from the five subjects who received long-term treatment. Results: TEMT administration was completely safe over the 2½-year period, with no deleterious side effects. In six cognitive/functional tasks (including the ADAS-cog13, Rey AVLT, MMSE, and ADL), no decline in any measure occurred over this 2½-year period. Long-term TEMT induced reductions in the CSF levels of C-reactive protein, p-tau217, Aβ1-40, and Aβ1-42 while modulating CSF oligomeric Aβ levels. In the plasma, long-term TEMT modulated/rebalanced levels of both p-tau217 and total tau. Conclusions: Although only a limited number of AD patients were involved in this study, the results suggest that TEMT can stop the cognitive decline of AD over a period of at least 2½ years and can do so with no safety issues. [ABSTRACT FROM AUTHOR]

Background: The ability to understand emotions is often disturbed in patients with cognitive impairments. Right temporal lobe structures play a crucial role in emotional processing, especially the amygdala, temporal pole (TP), superior temporal sulcus (STS), and anterior cingulate (AC). Those regions are affected in early stages of Alzheimer´s disease (AD). The aim of our study was to evaluate emotional prosody recognition (EPR) in participants with amnestic mild cognitive impairment (aMCI) due to AD, AD dementia patients, and cognitively healthy controls and to measure volumes or thickness of the brain structures involved in this process. In addition, we correlated EPR score to cognitive impairment as measured by MMSE. The receiver operating characteristic (ROC) analysis was used to assess the ability of EPR tests to differentiate the control group from the aMCI and dementia groups. Methods: Eighty-nine participants from the Czech Brain Aging Study: 43 aMCI due to AD, 36 AD dementia, and 23 controls, underwent Prosody Emotional Recognition Test. This experimental test included the playback of 25 sentences with neutral meaning each recorded with different emotional prosody (happiness, sadness, fear, disgust, anger). Volume of the amygdala and thickness of the TP, STS, and rostral and caudal parts of AC (RAC and CAC) were measured using FreeSurfer algorithm software. ANCOVA was used to evaluate EPR score differences. ROC analysis was used to assess the ability of EPR test to differentiate the control group from the aMCI and dementia groups. The Pearson's correlation coefficients were calculated to explore relationships between EPR scores, structural brain measures, and MMSE. Results: EPR was lower in the dementia and aMCI groups compared with controls. EPR total score had high sensitivity in distinguishing between not only controls and patients, but also controls and aMCI, controls and dementia, and aMCI and dementia. EPR decreased with disease severity as it correlated with MMSE. There was a significant positive correlation of EPR and thickness of the right TP, STS, and bilateral RAC. Conclusions: EPR is impaired in AD dementia and aMCI due to AD. These data suggest that the broad range of AD symptoms may include specific deficits in the emotional sphere which further complicate the patient's quality of life. [ABSTRACT FROM AUTHOR]

Cognitive reserve (CR) may reduce the risk of dementia. We summarized the effect of CR on progression to mild cognitive impairment (MCI) or dementia in studies accounting for Alzheimer's disease (AD)-related structural pathology and biomarkers. Literature search was conducted in Web of Science, PubMed, Embase, and PsycINFO. Relevant articles were longitudinal, in English, and investigating MCI or dementia incidence. Meta-analysis was conducted on nine articles, four measuring CR as cognitive residual of neuropathology and five as composite psychosocial proxies (e.g., education). High CR was related to a 47% reduced relative risk of MCI or dementia (pooled-hazard ratio: 0.53 [0.35, 0.81]), with residual-based CR reducing risk by 62% and proxy-based CR by 48%. CR protects against MCI and dementia progression above and beyond the effect of AD-related structural pathology and biomarkers. The finding that proxy-based measures of CR rivaled residual-based measures in terms of effect on dementia incidence underscores the importance of early- and mid-life factors in preventing dementia later. [ABSTRACT FROM AUTHOR]

Background: The apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory and spatial navigation deficits. The brain-derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment in APOEɛ4 carriers but its role in APOEɛ4-related spatial navigation deficits has not been established.Objective: We examined influence of APOE and BDNF Val66Met polymorphism combination on spatial navigation and volumes of selected navigation-related brain regions in cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (aMCI).Methods: 187 participants (aMCI [n = 116] and CU [n = 71]) from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4-/BDNFVal/Val, ɛ4-/BDNFMet, ɛ4+/BDNFVal/Val, and ɛ4+/BDNFMet. The participants underwent comprehensive neuropsychological examination, brain MRI, and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real-space human analogue of the Morris water maze.Results: Among the aMCI participants, the ɛ4+/BDNFMet group had the least accurate egocentric navigation performance (p < 0.05) and lower verbal memory performance than the ɛ4-/BDNFVal/Val group (p = 0.007). The ɛ4+/BDNFMet group had smaller hippocampal and entorhinal cortical volumes than the ɛ4-/BDNFVal/Val (p≤0.019) and ɛ4-/BDNFMet (p≤0.020) groups. Among the CU participants, the ɛ4+/BDNFMet group had less accurate allocentric and allocentric delayed navigation performance than the ɛ4-/BDNFVal/Val group (p < 0.05).Conclusion: The combination of APOEɛ4 and BDNF Met polymorphisms is associated with more pronounced egocentric navigation impairment and atrophy of the medial temporal lobe regions in individuals with aMCI and less accurate allocentric navigation in CU older adults. [ABSTRACT FROM AUTHOR]

Background: The hippocampus, entorhinal cortex, and basal forebrain are among the first brain structures affected by Alzheimer's disease (AD). They play an essential role in spatial pattern separation, a process critical for accurate encoding of similar spatial information.Objective: Our aim was to examine spatial pattern separation and its association with volumetric changes of the hippocampus, entorhinal cortex, and basal forebrain nuclei projecting to the hippocampus (the medial septal nuclei and vertical limb of the diagonal band of Broca - Ch1-2 nuclei) in the biomarker-defined early clinical stages of AD.Methods: A total of 98 older adults were recruited from the Czech Brain Aging Study cohort. The participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 44), mild AD dementia (n = 31), and cognitively normal older adults (CN; n = 23) underwent spatial pattern separation testing, comprehensive cognitive assessment, and MRI brain volumetry.Results: Spatial pattern separation accuracy was lower in the early clinical stages of AD compared to the CN group (p < 0.001) and decreased with disease severity (CN > aMCI due to AD > AD dementia). Controlling for general memory and cognitive performance, demographic characteristics and psychological factors did not change the results. Hippocampal and Ch1-2 volumes were directly associated with spatial pattern separation performance while the entorhinal cortex operated on pattern separation indirectly through the hippocampus.Conclusion: Smaller volumes of the hippocampus, entorhinal cortex, and basal forebrain Ch1-2 nuclei are linked to spatial pattern separation impairment in biomarker-defined early clinical AD and may contribute to AD-related spatial memory deficits. [ABSTRACT FROM AUTHOR]

Apolipoprotein (APOE) ɛ4 is a well-known risk factor for late-onset Alzheimer's disease (AD), but other AD-related gene polymorphisms might also be important, such as the polymorphism within the brain-derived neurotrophic factor (BDNF) gene. Carriage of BDNF Val66Met has been associated with faster cognitive decline and greater hippocampal atrophy in cognitively normal elderly. Thus, we examined the effects of the concurrent presence of APOE and BDNF polymorphisms on cognitive functions and brain morphometry in amnestic mild cognitive impairment (aMCI) patients. 107 aMCI patients (mean age = 72.2) were recruited from the Czech Brain Aging Study and, based on APOE and BDNF genes polymorphisms, were divided into four groups: ɛ4-BDNFVal/Val (n = 37), ɛ4-BDNFMet (n = 19), ɛ4+BDNFVal/Val (n = 35), and ɛ4+BDNFMet (n = 16). All patients underwent clinical examination, magnetic resonance imaging, and complex neuropsychological battery. The combination of APOEɛ4+ and BDNF Met was associated with significantly worse memory performance in immediate and delayed recall compared to other polymorphism groups. We did not observe increased atrophy in areas related to memory function in the ɛ4+BDNFMet group. Our findings suggest that carriage of ɛ4+BDNFMet is associated with more pronounced memory dysfunction, a typical feature of early AD, but not with structural brain changes in aMCI patients. These findings suggest that in APOEɛ4/BDNF Met carriers, synaptic dysfunction affecting memory may precede pronounced structural changes. [ABSTRACT FROM AUTHOR]

Background: Small aggregates (oligomers) of the toxic proteins amyloid-β (Aβ) and phospho-tau (p-tau) are essential contributors to Alzheimer's disease (AD). In mouse models for AD or human AD brain extracts, Transcranial Electromagnetic Treatment (TEMT) disaggregates both Aβ and p-tau oligomers, and induces brain mitochondrial enhancement. These apparent "disease-modifying" actions of TEMT both prevent and reverse memory impairment in AD transgenic mice.Objective: To evaluate the safety and initial clinical efficacy of TEMT against AD, a comprehensive open-label clinical trial was performed.Methods: Eight mild/moderate AD patients were treated with TEMT in-home by their caregivers for 2 months utilizing a unique head device. TEMT was given for two 1-hour periods each day, with subjects primarily evaluated at baseline, end-of-treatment, and 2 weeks following treatment completion.Results: No deleterious behavioral effects, discomfort, or physiologic changes resulted from 2 months of TEMT, as well as no evidence of tumor or microhemorrhage induction. TEMT induced clinically important and statistically significant improvements in ADAS-cog, as well as in the Rey AVLT. TEMT also produced increases in cerebrospinal fluid (CSF) levels of soluble Aβ1-40 and Aβ1-42, cognition-related changes in CSF oligomeric Aβ, a decreased CSF p-tau/Aβ1-42 ratio, and reduced levels of oligomeric Aβ in plasma. Pre- versus post-treatment FDG-PET brain scans revealed stable cerebral glucose utilization, with several subjects exhibiting enhanced glucose utilization. Evaluation of diffusion tensor imaging (fractional anisotropy) scans in individual subjects provided support for TEMT-induced increases in functional connectivity within the cognitively-important cingulate cortex/cingulum.Conclusion: TEMT administration to AD subjects appears to be safe, while providing cognitive enhancement, changes to CSF/blood AD markers, and evidence of stable/enhanced brain connectivity. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive complaints (SCCs) may be an early marker of prodromal Alzheimer's disease.Objectives: Using a 10-item yes/no SCCs questionnaire (Le Questionnaire de Plainte Cognitive [QPC]), we evaluated the prevalence and distribution of SCCs in cognitively healthy Czech older adults and examined total score and specific QPC items in relation to depressive symptomology and cognitive performance.Methods: A sample of 340 cognitively healthy older community-dwelling volunteers aged 60 or older from the third wave of the longitudinal project National Normative Study of Cognitive Determinants of Healthy Aging, who underwent a comprehensive neuropsychological assessment and completed the QPC and the 15-item Geriatric Depression Scale (GDS-15). Regression analysis was controlled for age when GDS-15 was the outcome and for age and GDS-15 with cognitive domains as the outcome.Results: 71% reported 1 + SCCs, with prevalence of individual complaints ranging from 4% to 40%. The number of SCCs was associated with GDS-15 (p < 0.001). Personality change (p < 0.001) and Limitation in daily activities (p = 0.002) were significantly associated with higher GDS-15 score and Spatial orientation difficulties (p = 0.019) and Impression of worse memory in comparison to peers (p = 0.012) were significantly associated with lower memory performance.Conclusions: We identified some cognitive complaints that were very common in our sample. Overall, a higher number of SCCs in well cognitively functioning individuals was most closely related to depressive symptomatology, while some specific complaints reflected lower memory performance and should be considered when screening for people at risk of cognitive decline. [ABSTRACT FROM AUTHOR]

Spatial navigation (SN) impairment is present early in Alzheimer's disease (AD). We tested whether SN performance, self-centered (egocentric) and world-centered (allocentric), was distinguishable from performance on established cognitive functions—verbal and nonverbal memory, executive and visuospatial function, attention/working memory, and language function. 108 older adults (53 cognitively normal [CN] and 55 with amnestic mild cognitive impairment [aMCI]) underwent neuropsychological examination and real-space navigation testing. Subset (n = 63) had automated hippocampal volumetry. In a factor analysis, allocentric and egocentric navigation tasks loaded highly onto the same factor with low loadings on other factors comprising other cognitive functions. In linear regression, performance on other cognitive functions was not, or was only marginally, associated with spatial navigation performance in CN or aMCI groups. After adjustment for age, gender, and education, right hippocampal volume explained 26% of the variance in allocentric navigation in aMCI group. In conclusion, spatial navigation, a known cognitive marker of early AD, may be distinguished from other cognitive functions. Therefore, its assessment along with other major cognitive functions may be highly beneficial in terms of obtaining a comprehensive neuropsychological profile. [ABSTRACT FROM AUTHOR]

Background: High plasma homocysteine (Hcy) level is related to higher risk of Alzheimer's disease (AD) and lower cognitive performance in older adults.Objective: To assess the association between plasma Hcy level and real-space navigation performance and the role of vascular risk and protective factors, APOE status, and white matter lesions (WML) on this association.Methods: Ninety-two non-demented older adults (29 with amnestic mild cognitive impairment, 46 with subjective cognitive decline, and 17 cognitively normal older adults) underwent spatial navigation testing of egocentric, allocentric, and mixed navigation in a real-space analogue of the Morris water maze, neuropsychological examination, blood collection, and MRI brain scan with evaluation of WML.Results: In the regression analyses controlling for age, gender, education, and depressive symptoms, higher plasma Hcy level was related to worse mixed and egocentric (β= 0.31; p = 0.003 and β= 0.23; p = 0.017) but not allocentric (p > 0.05) navigation performance. Additional controlling for vascular risk and protective factors, WML, and APOE status did not modify the results. High total cholesterol and low vitamin B12 and folate levels increased the adverse effect of Hcy on egocentric and mixed navigation. WML did not explain the association between plasma Hcy level and navigation performance.Conclusion: Elevated plasma Hcy level may affect real-space navigation performance above and beyond vascular brain changes. This association may be magnified in the presence of high total cholesterol and low folate or vitamin B12 levels. Attention to the level of plasma Hcy may be a viable intervention strategy to prevent decline in spatial navigation in non-demented older adults. [ABSTRACT FROM AUTHOR]

The very long (VL) poly-T variant at rs10524523 (“523”) of the TOMM40 gene may hasten the onset of late-onset Alzheimer’s disease (LOAD) and induce more profound cognitive impairment compared with the short (S) poly-T variant. We examined the influence of TOMM40 “523” polymorphism on spatial navigation and its brain structural correlates. Participants were apolipoprotein E (APOE) ε3/ε3 homozygotes with amnestic mild cognitive impairment (aMCI). The homozygotes were chosen because APOE ε3/ε3 variant is considered “neutral” with respect to LOAD risk. The participants were stratified according to poly-T length polymorphisms at “523” into homozygous for S (S/S; n = 16), homozygous for VL (VL/VL; n = 15) TOMM40 poly-T variant, and heterozygous (S/VL; n = 28) groups. Neuropsychological examination and testing in real-space human analog of the Morris Water Maze were administered. Both self-centered (egocentric) and world-centered (allocentric) spatial navigation was assessed. Brain magnetic resonance imaging scans were analyzed using FreeSurfer software. The S/S group, although similar to S/VL and VL/VL groups in demographic and neuropsychological profiles, performed better on allocentric navigation ( p ≤ 0.004) and allocentric delayed recall ( p ≤ 0.014), but not on egocentric navigation. Both S/VL and VL/VL groups had thinner right entorhinal cortex ( p ≤ 0.043) than the S/S group, whereas only the VL/VL group had thinner left entorhinal cortex ( p = 0.043) and left posterior cingulate cortex ( p = 0.024) than the S/S group. In conclusion, TOMM40 “523” VL variants are related to impairment in allocentric spatial navigation and reduced cortical thickness of specific brain regions among aMCI individuals with (LOAD neutral) APOE ε3/ε3 genotype. This may reflect a specific role of TOMM40 “523” in the pathogenesis of LOAD. [ABSTRACT FROM AUTHOR]

Older age is associated with changes in the brain, including the medial temporal lobe, which may result in mild spatial navigation deficits, especially in allocentric navigation. The aim of the study was to characterize the profile of real-space allocentric (world-centered, hippocampus-dependent) and egocentric (body-centered, parietal lobe dependent) navigation and learning in young vs. older adults, and to assess a possible influence of gender. We recruited healthy participants without cognitive deficits on standard neuropsychological testing, white matter lesions or pronounced hippocampal atrophy: 24 young participants (18-26 years old) and 44 older participants stratified as participants 60-70 years old (n = 24) and participants 71-84 years old (n = 20). All underwent spatial navigation testing in the real-space human analog of the MorrisWater Maze, which has the advantage of assessing separately allocentric and egocentric navigation and learning. Of the eight consecutive trials, trials 2-8 were used to reduce bias by a rebound effect (more dramatic changes in performance between trials 1 and 2 relative to subsequent trials). The participants who were 71-84 years old (p < 0.001), but not those 60-70 years old, showed deficits in allocentric navigation compared to the young participants. There were no differences in egocentric navigation. All three groups showed spatial learning effect (p' s ⩽ 0.01). There were no gender differences in spatial navigation and learning. Linear regression limited to older participants showed linear (β = 0.30, p = 0.045) and quadratic (β = 0.30, p = 0.046) effect of age on allocentric navigation.There was no effect of age on egocentric navigation. These results demonstrate that navigation deficits in older age may be limited to allocentric navigation, whereas egocentric navigation and learning may remain preserved. This specific pattern of spatial navigation impairment may help differentiate normal aging from prodromal Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = -0.62, P < 0.001) and virtual (β = -0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present. [ABSTRACT FROM AUTHOR]

Background: The effect of APOE ε4 allele (ε4) on spatial navigation in amnestic mild cognitive impairment (aMCI) is unknown. Objective: Our purpose was to examine the characteristics of spatial navigation impairment in ε4-positive (ε4+) and ε4-negative (ε4-) aMCI subgroups. Methods: Blood samples were collected to determine the APOE genotype. A total of 34 aMCI patients were stratified into aMCI-ε4- (n = 23) and aMCI-ε4+ (n = 11) groups. Control (n = 28) and mild Alzheimer's disease (AD; n = 16) groups were also used. We used a human analogue of the Morris water maze (enclosed arena 2.9 m in diameter) to examine body-centered (egocentric) and world-centered (allocentric) spatial navigation. Results: The aMCI-ε4+ group performed poorer on spatial navigation than the aMCI-ε4- group in both egocentric and allocentric tasks even though these 2 groups did not differ in global cognitive functioning or neuropsychological tests. The aMCI-ε4+ and mild AD groups performed similarly on all Morris Water Maze tasks and were outperformed by the aMCI-ε4- group, which also resembled the control group in performance on the egocentric tasks. The aMCI groups showed poor spatial navigation learning regardless of their ε4 positivity. Conclusion: We found more profound deficits in spatial navigation in aMCI-ε4+ relative to aMCI-ε4- patients. The aMCI-ε4+ group resembled the mild AD group in spatial navigation performance. Although the ε4 genotype was indicative of spatial navigation performance, it was not indicative of the aMCI patients' ability to learn the tasks. Spatial navigation testing represents a promising area with respect to identifying individuals at higher risk for AD among the heterogeneous MCI population. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. We examined the association between extremely low-frequency magnetic fields (EMF) and the risk of dementia and Alzheimer’s disease using all 9,508 individuals from the Study of Dementia in Swedish Twins (HARMONY) with valid occupational and diagnostic data. Methods. Dementia diagnoses were based on telephone screening followed by in-person clinical workup. Main lifetime occupation was coded according to an established EMF exposure matrix. Covariates were age, gender, education, vascular risk factors, and complexity of work. Based on previous research, data were also analyzed separately for cases with disease onset by age 75 years versus later, men versus women, and those with manual versus nonmanual main occupation. We used generalized estimating equations with the entire sample (to adjust for the inclusion of complete twin pairs) and conditional logistic regression with complete twin pairs only. Results. Level of EMF exposure was not significantly associated with dementia or Alzheimer’s disease. However, in stratified analyses, medium and high levels of EMF exposure were associated with increased dementia risk compared with low level in cases with onset by age 75 years (odds ratio: 1.94, 95% confidence interval: 1.07–3.65 for medium, odds ratio: 2.01, 95% confidence interval: 1.10–3.65 for high) and in participants with manual occupations (odds ratio: 1.81, 95% confidence interval: 1.06–3.09 for medium, odds ratio: 1.75, 95% confidence interval: 1.00–3.05 for high). Results with 42 twin pairs discordant for dementia did not reach statistical significance. Conclusions. Occupational EMF exposure appears relevant primarily to dementia with an earlier onset and among former manual workers. [ABSTRACT FROM PUBLISHER]

We examined the association between risk of dementia or Alzheimer's disease (AD) and occupation by using measures of complexity of work with data, people, and things. The study included 10,079 members of the population-based Swedish Twin Registry who were participants in the HARMONY study. We diagnosed dementia by means of a two-stage procedure—cognitive impairment screening followed by full clinical evaluation. We analyzed data with case-control and cotwin control designs. The cotwin control design provides control over genetic and familial factors. In the case-control study, controlling for age, gender, and level of education, we found that more complex work with people was associated with reduced risk of AD. Greater complexity of work with people and data was protective in twin pairs discordant for AD. Findings suggest that greater complexity of work, and particularly complex work with people, may reduce the risk of AD. [ABSTRACT FROM AUTHOR]

Reports on a study by researchers in Sweden, which suggest that greater engagement in leisure activities during early and middle adulthood may protect against Alzheimer's disease and dementia in general. Limitations and strength of the study; Effects of greater intellectual ability on the types of activities that people participate.

Background Evaluation of patients for Alzheimer's disease often compares an individual's performance on cognitive tests to established norms. The purpose of this study was to compare performance on the CERAD Word List Memory tasks in normal controls from an Alzheimer's disease registry and in community volunteers. Methods Scores on Word List Memory tasks were evaluated in cognitively intact participants enrolled in a university-based Alzheimer's disease registry (n =103) and in a sample of community volunteers (n =51). Scores for the two samples were also compared with previously published data from registry-based normal controls and from a representative community-based sample. Results University-based participants outperformed community volunteers, with most marked differences on Delayed Recall and on a Savings score that contrasted immediate to delayed recall. University-based participants performed similarly to previously published scores for normal controls from another university-based Alzheimer's disease registry, while community volunteers were consistent with published scores available from a representative community sample. Conclusions Accurate neuropsychological assessment of Alzheimer's disease may require consideration of potentially subtle differences between older adults tested at university centers and those tested in the community. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Three experiments examined the role of visual feedback on the performance of a fine motor task, namely the rotary pursuit, in patients with Alzheimer's disease (AD) and healthy older adults. After extensive practice tracking a fully visible target, participants in Experiments 1 and 2 were tested under restricted vision (RV) conditions. In both experiments, the two groups showed a drop in performance when vision was restricted, with AD patients showing a significantly larger decline. Tracking improved significantly in normal controls, but not AD patients across the RV trials after the initial drop. When difficulty of the rotary pursuit task was manipulated in Experiment 3 without restricting vision, AD patients and normal controls showed identical patterns of performance. Consequently, it could be concluded that AD patients in the first two experiments were relying more heavily on visual information for accurate performance of the tracking task than their healthy peers. [ABSTRACT FROM AUTHOR]

This study examined the acquisition, retention, and transfer of a gross motor skill, namely, tossing, in 84 moderate-to-severely demented patients with Alzheimer’s disease (AD) and 72 healthy elderly controls. To identify optimal learning strategies, participants received 10 weeks of training under 1 of 5 practice conditions: constant, variable-parameter, variable-program, variable-combined, or no training. Constant practice was the only training condition that significantly enhanced learning and near transfer in AD patients. In comparison, all 4 types of training facilitated acquisition and near transfer in the healthy controls, with variable-combined practice being the most beneficial. The superiority of the variable practice conditions in the healthy controls supports both Schmidt’s (1975) variability of practice hypothesis and contextual interference theory. The inability of AD patients to benefit from variable forms of practice suggests that these impaired individuals may have difficulty accessing and/or forming motor schemas. [ABSTRACT FROM AUTHOR]

Perspective taking is the ability to imagine what a scene looks like from a different viewpoint, which has been reported to be impaired in Alzheimer's disease (AD). This study compared overhead and first-person view perspective taking abilities in patients with mild cognitive impairment (MCI) and AD. A newly developed Arena Perspective Taking Task (APTT), using an environment of a circular arena, was used to compare 23 AD patients and 38 amnestic MCI patients with 18 healthy controls. The results were contrasted with a published perspective taking test (Standardized Road-Map Test of Direction Sense, RMTDS). The AD group was impaired in both overhead and first-person view APTT versions, but the impairment in the overhead view version applied specifically to women. Patients with aMCI were impaired in the first-person view but not in the overhead view version. Substantial sexual differences were found in the overhead but not in the first-person view APTT version. The RMTDS resembled both APTT versions: patients with aMCI were impaired in this test and also women in both patient groups were less accurate than men. Using the receiver operating characteristic analysis, the highest predictive power for MCI and AD patients diagnosis versus controls was observed for their success rate in the first-person view version. The results suggest distinction between overhead and first-person view perspective taking in the impairment of aMCI patients and the sex differences. The first-person view perspective taking is a potentially important candidate psychological marker for AD. [ABSTRACT FROM AUTHOR]

Background Olfactory identification impairment in amnestic mild cognitive impairment (aMCI) patients is well documented and considered to be caused by underlying Alzheimer's disease (AD) pathology, contrasting with less clear evidence in non-amnestic MCI (naMCI). The aim was to (a) compare the degree of olfactory identification dysfunction in aMCI, naMCI, controls and mild AD dementia and (b) assess the relation between olfactory identification and cognitive performance in aMCI compared to naMCI. Methods 75 patients with aMCI and 32 with naMCI, 26 patients with mild AD and 27 controls underwent the multiple choice olfactory identification Motol Hospital Smell Test with 18 different odors together with a comprehensive neuropsychological examination. Results Controlling for age and gender, patients with aMCI and naMCI did not differ significantly in olfactory identification and both performed significantly worse than controls (p < 0.001), albeit also better than patients with mild AD (p < .001). In the aMCI group, higher scores on MMSE, verbal and non-verbal memory and visuospatial tests were significantly related to better olfactory identification ability. Conversely, no cognitive measure was significantly related to olfactory performance in naMCI. Conclusion Olfactory identification is similarly impaired in aMCI and naMCI. Olfactory impairment is proportional to cognitive impairment in aMCI but not in naMCI. [ABSTRACT FROM AUTHOR]

Abstract: The hippocampus is essential for consolidation of declarative information and spatial navigation. Alzheimer''s disease (AD) diagnosis tends to be preceded by a long prodromal period and mild cognitive impairment (MCI). Our goal was to test whether amnestic MCI comprises two different subgroups, with hippocampal and non-hippocampal memory impairment, that vary with respect to spatial navigation ability. A total of 52 patients were classified into two subgroups: non-amnestic MCI (naMCI) (n =10) and amnestic MCI (aMCI) (n =42). The aMCI subgroup was further stratified into memory impairment of hippocampal type—hippocampal aMCI (HaMCI) (n =10) (potential preclinical AD) and isolated retrieval impairment—non-hippocampal (NHaMCI) (n =32). Results were compared to control (n =28) and AD (n =21) groups. We used the Hidden Goal Task, a human analogue of the Morris Water Maze, to examine spatial navigation either dependent (egocentric) or independent of individual''s position (allocentric). Overall, the HaMCI group performed poorer on spatial navigation than the NHaMCI group, especially in the latter trials when the HaMCI group exhibited limited capacity to learn and the NHaMCI group exhibited a learning effect. Finally, the HaMCI group performed almost identically as the AD group. Spatial navigation deficit is particularly pronounced in individuals with hippocampus-related memory impairment and may signal preclinical AD. [Copyright &y& Elsevier]