Early Alzheimer's Dementia Research Articles

Genetic factors of early Alzheimer's dementia

Alzheimer's disease (AD) is classified as a neurodegenerative disorder that alters the memory and cognitive capacity of the affected individual, in addition to causing behavioral changes and other neuropsychiatric symptoms. In this work, genes involved in the metabolism of this neurodegenerative disorder were reported, as well as their positioning on their chromosomes with an emphasis on the human genome. The following research sources were used to collect data and results: scientific articles, books and websites specializing in this subject regarding AD and the human genome. The result of this investigation indicated that the genes studied are located on chromosomes 1, 14, 17, 19 and 21 in the human genome, and associated with early AD disease in humans. Therefore, the identification of genes related to AD is necessary for a better understanding of AD genetics and also for the development of molecular markers of therapeutic targets for the diagnosis and treatment of this dementia.

Letter to Our Colleagues Family Practitioners, Geriatricians, and Radiologists to Increase Awareness Regarding Idiopathic Normal Pressure Hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) affects elderly individuals and is characterized by a progressive deterioration of gait, urinary continence, and cognition. In most cases, it is reversible with treatment. INPH is not uncommonly an unrecognized cause of dementia. We wish to raise awareness of iNPH among primary care providers who are seeing these patients first. We reviewed the current epidemiological data regarding iNPH as well as epidemiological data regarding Alzheimer disease. We searched for the most sensitive radiological screening test for iNPH. Alzheimer disease comprises 60%-70% of all dementia cases, in 2023 is affecting 6.7 million Americans, about 10.7% of people 65 and older. Epidemiological data from the Scandinavian countries confirmed that 3.7% of people older than 65 have iNPH. Surgical studies confirmed the presence of early Alzheimer's pathology in about 25% of operated patients with iNPH. Useful radiological findings of iNPH include an Evans Index greater than 0.30, and a disproportionally enlarged subarachnoid space hydrocephalus (DESH). However, the callosal angle is thought to represent the best tool to discriminate iNPH from its mimics. According to the available epidemiological data iNPH is underdiagnosed. We strongly encourage the primary care physicians and geriatricians to ask the radiologist to measure the callosal angle on the initial brain computed tomography (or magnetic resonance) image. If the callosal angle is ≤71°, it is appropriate to refer the patient to neurosurgery for further diagnostic work-up.

Low-Dose Whole Brain Radiation Therapy for Alzheimer's Dementia: Results From a Pilot Trial in Humans

We report neurocognitive, imaging, ophthalmologic, and safety outcomes following low-dose whole brain radiation therapy (LD-WBRT) for patients with early Alzheimer dementia (eAD) treated in a pilot trial. Trial-enrolled patients were at least 55 years of age, had eAD meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) Alzheimer's Criteria with confirmatory fluorodeoxyglucose and florbetapir positron emission tomography findings; had the capacity to complete neurocognitive function, psychological function, and quality-of-life assessments; had a Rosen modified Hachinski score ≤4; and had estimated survival >12 months. Five patients were treated with LD-WBRT (2 Gy × 5 over 1 week; 3 female; mean age, 73.2 years [range, 69-77]). Four of 5 patients had improved (n = 3) or stable (n = 1) Mini-Mental State Examination (second edition) T-scores at 1 year. The posttreatment scores of all 3 patients who improved increased to the average range. There were additional findings of stability of naming and other cognitive skills as well as stability to possible improvement in imaging findings. No safety issues were encountered. The only side effect was temporary epilation with satisfactory hair regrowth. Our results from 5 patients with eAD treated with LD-WBRT (10 Gy in 5 fractions) demonstrate a positive safety profile and provide preliminary, hypothesis-generating data to suggest that this treatment stabilizes or improves cognition. These findings will require further evaluation in larger, definitive, randomized trials.

Cognitive decline and hippocampal functional connectivity within older Black adults.

While there has been a proliferation of neuroimaging studies on cognitive decline in older non‐Hispanic White adults, there is a dearth of knowledge regarding neuroimaging correlates of cognitive decline in Black adults. Resting‐state functional neuroimaging approaches may be particularly sensitive to early cognitive decline, but there are no studies that we know of that apply this approach to examining associations of brain function to cognition in older Black adults. We investigated the association of cognitive decline with whole‐brain voxel‐wise functional connectivity to the hippocampus, a key brain region functionally implicated in early Alzheimer's dementia, in 132 older Black adults without dementia participating in the Minority Aging Research Study and Rush Memory and Aging Project, two longitudinal studies of aging that include harmonized annual cognitive assessments and magnetic resonance imaging brain imaging. In models adjusted for demographic factors (age, education, sex), global cognitive decline was associated with functional connectivity of the hippocampus to three clusters in the right and left frontal regions of the dorsolateral prefrontal cortex. In domain‐specific analyses, decline in semantic memory was associated with functional connectivity of the hippocampus to bilateral clusters in the precentral gyrus, and decline in perceptual speed was inversely associated with connectivity of the hippocampus to the bilateral intracalcarine cortex and the right fusiform gyrus. These findings elucidate neurobiological mechanisms underlying cognitive decline in older Black adults and may point to specific targets of intervention for Alzheimer's disease.

Moving in Semantic Space in Prodromal and Very Early Alzheimer's Disease: An Item-Level Characterization of the Semantic Fluency Task.

The semantic fluency task is a widely used clinical tool in the diagnostic process of Alzheimer's disease. The task requires efficient mapping of the semantic space to produce as many items as possible within a semantic category. We examined whether healthy volunteers (n = 42) and patients with early Alzheimer's disease (24 diagnosed with amnestic Mild Cognitive Impairment and 18 with early Alzheimer's dementia) take advantage of and travel in the semantic space differently. With focus on the animal fluency task, we sought to emulate the detailed structure of the multidimensional semantic space by utilizing word2vec-method from the natural language processing domain. To render the resulting multidimensional semantic space visually comprehensible, we applied a dimensionality reduction algorithm (t-SNE), which enabled a straightforward division of the semantic space into sub-categories. Moving in semantic space was quantified with the number of items created, sub-categories visited, and switches and returns to these sub-categories. Multinomial logistic regression models were used to predict the diagnostic group with these independent variables. We found that returning to a sub-category provided additional information, besides the number of words produced in the task, to differentiate patients with Alzheimer's dementia from both amnestic Mild Cognitive Impairment patients and healthy controls. The results suggest that the frequency of returning to a sub-category may serve as an additional aid for clinicians in diagnosing early Alzheimer's disease. Moreover, our results imply that the combination of word2vec and subsequent t-SNE-visualization may offer a valuable tool for examining the semantic space and its sub-categories.

Validation of Picture Free and Cued Selective Reminding Test for Illiteracy in Lima, Peru.

Dementia in Latin America is a crucial public health problem. Identifying brief cognitive screening (BCS) tools for the primary care setting is crucial, particularly for illiterate individuals. We evaluated tool performance characteristics and validated the free and total recall sections of the Free and Cued Selective Reminding Test-Picture version (FCSRT-Picture) to discriminate between 63 patients with early Alzheimer's disease dementia (ADD), 60 amnestic mild cognitive impairment (aMCI) and 64 cognitively healthy Peruvian individuals with illiteracy from an urban area. Clinical, functional, and cognitive assessments were performed. FCSRT-Picture performance was assessed using receiver operating characteristic curve analyses. The mean ± standard deviation scores were 7.7 ± 1.0 in ADD, 11.8 ± 1.6 in aMCI, and 29.5 ± 1.8 in controls. The FCSRT-Picture had better performance characteristics for distinguishing controls from aMCI compared with several other BCS tools, but similar characteristics between controls and early ADD. The FCSRT-Picture is a reliable BCS tool for illiteracy in Peru.

Longitudinal Cognitive Profiles by Anxiety and Depressive Symptoms in American Older Adults With Subjective Cognitive Decline.

The objective of this study was to determine how anxiety and/or depressive symptoms differentially affect specific cognitive domains over time in persons with subjective cognitive decline (SCD). A longitudinal, observational study was conducted using data from the National Alzheimer's Coordinating Center-Uniform Data Set. Mean follow-up was 4.1±2.4years. Using information from a total of 1401 participants (age 74.0±8.2years), linear mixed-effects regression models were used to assess longitudinal changes in global cognition, episodic memory, attention, language, and executive function by baseline psychological (anxiety [A] and/or depressive [D]) symptoms in individuals with SCD. Reference was the group having no symptoms (A-/D-). The A+/D- group was not associated with any cognitive changes. The A-/D+ group was associated with a greater decline in episodic memory and executive function. The A+/D+ group had a greater decline in attention. Changes in global cognition and language were not predicted by any psychological symptoms. Depressive symptoms predicted lower episodic memory and executive function. Nurses need to pay attention to depressive symptoms in older adults with SCD because managing depressive symptoms may help protect against cognitive decline more typical of early Alzheimer's dementia.

Association of Digital Clock Drawing With PET Amyloid and Tau Pathology in Normal Older Adults.

To determine whether a digital clock-drawing test, DCTclock, improves upon standard cognitive assessments for discriminating diagnostic groups and for detecting biomarker evidence of amyloid and tau pathology in clinically normal older adults (CN). Participants from the Harvard Aging Brain Study and the PET laboratory at Massachusetts General Hospital were recruited to undergo the DCTclock, standard neuropsychological assessments including the Preclinical Alzheimer Cognitive Composite (PACC), and amyloid/tau PET imaging. Receiver operating curve analyses were used to assess diagnostic and biomarker discriminability. Logistic regression and partial correlations were used to assess DCTclock performance in relation to PACC and PET biomarkers. A total of 300 participants were studied. Among the 264 CN participants, 143 had amyloid and tau PET imaging (Clinical Dementia Rating [CDR] 0, Mini-Mental State Examination [MMSE] 28.9 ± 1.2). An additional 36 participants with a diagnosis of mild cognitive impairment or early Alzheimer dementia (CDR 0.5, MMSE 25.2 ± 3.9) were added to assess diagnostic discriminability. DCTclock showed excellent discrimination between diagnostic groups (area under the receiver operating characteristic curve 0.86). Among CN participants with biomarkers, the DCTclock summary score and spatial reasoning subscores were associated with greater amyloid and tau burden and showed better discrimination (Cohen d = 0.76) between Aβ± groups than the PACC (d = 0.30). DCTclock discriminates between diagnostic groups and improves upon traditional cognitive tests for detecting biomarkers of amyloid and tau pathology in CN older adults. The validation of such digitized measures has the potential of providing an efficient tool for detecting early cognitive changes along the AD trajectory. This study provides Class II evidence that DCTclock results were associated with amyloid and tau burden in CN older adults.

Does resting state functional connectivity differ between mild cognitive impairment and early Alzheimer's dementia?

PurposeThis study aimed to investigate differences in functional connectivity (FC) among different resting state networks (RSN) in clinically non-progressive mild cognitive impairment (MCI) and Alzheimer's disease (AD). MethodsUsing 3T MRI acquired resting-state functional MRI (rs-fMRI), we attempted identification of different RSN using independent component analysis (ICA) in amnestic-MCI, convertors to early AD and age-matched cognitively normal healthy controls. Regions of interest (ROI) that showed significant differences in connectivity on group ICA were selected as seeds for seed-voxel analysis. Group differences in FC for each network-connectivity map were entered into a general linear model with age, gender and total intra-cranial volume (TIV) as covariates. ResultsIn this cross-sectional design 31 HC, 30 MCI and 30 MCI-convertors to early AD were evaluated. Seed-based analysis between AD and controls revealed reduced posterior connectivity within the default mode (DMN), dorsal attention (DAN) and antero-posterior connectivity with sensori-motor (SMN) networks. Reduced cerebellar connectivity of DMN and posterior connectivity within the frontal parietal network (FPN) separated AD from MCI. MCI-control comparisons revealed differences only on ICA. Positive correlation was observed between FC in DMN network clusters with verbal list-learning (r = 0.50) and recall scores (r = 0.51) in AD, the latter additionally demonstrating correlation with SMN clusters (r = 0.50). ConclusionsWidespread network hypo-connectivity is apparent in AD as opposed to MCI non-convertors in comparison to controls, along with positive correlation with memory scores. Reduced connectivity involving DMN and FPN helps to differentiate between AD and MCI-nonconvertors to dementia. Longitudinal studies are required into utility of these measures.

Promising outcome measures of early Alzheimer's dementia in adults with Down syndrome.

IntroductionAdults with Down syndrome (DS) are at high risk for developing Alzheimer's disease (AD) and its associated dementia, warranting the development of strategies to improve early detection when prevention is possible.MethodsUsing a broad battery of neuropsychological assessments, informant interviews, and clinical record review, we evaluated the psychometrics of measures in a large sample of 561 adults with DS. We tracked longitudinal stability or decline in functioning in a subsample of 269 participants over a period of 3 years, all initially without indications of clinically significant aging‐related decline.ResultsResults identified an array of objective measures that demonstrated sensitivity in distinguishing individuals with incident “mild cognitive impairment” (MCI‐DS) as well as subsequent declines occurring with incident dementia.DiscussionSeveral instruments showed clear promise for use as outcome measures for future clinical trials and for informing diagnosis of individuals suspected of experiencing early signs and symptoms of a progressive dementia process.

Attentional ERPs distinguish aging and early Alzheimer's dementia.

The early detection of Alzheimer's disease requires our distinguishing it from cognitive aging. Here, we test whether spatial attentional changes might support that distinction. We engaged young normal (YN), older normal (ON), and patients with early Alzheimer's dementia (EAD) in an attentionally cued, self-movement heading discrimination task while we recorded push-button response times and event related potentials. YNs and ONs show the behavioral effects of attentional shifts from the cue to the target, whereas EAD patients did not (p < 0.001). YNs and ONs also show the shifting lateralization of a newly described attentional event related potentials component, whereas EAD patients did not (p < 0.001). Our findings suggest that spatial inattention in EAD patients may contribute to heading direction processing impairments that distinguish them from ONs and undermine their navigational capacity and driving safety.

Cognitive correlates of α4β2 nicotinic acetylcholine receptors in mild Alzheimer's dementia.

In early Alzheimer's dementia, there is a need for PET biomarkers of disease progression with close associations to cognitive dysfunction that may aid to predict further cognitive decline and neurodegeneration. Amyloid biomarkers are not suitable for that purpose. The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) are widely abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as attention, learning and memory. Post-mortem studies reported lower expression of α4β2-nAChRs in more advanced Alzheimer's dementia. However, there is ongoing controversy whether α4β2-nAChRs are reduced in early Alzheimer's dementia. Therefore, using the recently developed α4β2-nAChR-specific radioligand (-)-18F-flubatine and PET, we aimed to quantify the α4β2-nAChR availability and its relationship to specific cognitive dysfunction in mild Alzheimer's dementia. Fourteen non-smoking patients with mild Alzheimer's dementia, drug-naïve for cholinesterase therapy, were compared with 15 non-smoking healthy controls matched for age, sex and education by applying (-)-18F-flubatine PET together with a neuropsychological test battery. The one-tissue compartment model and Logan plot method with arterial input function were used for kinetic analysis to obtain the total distribution volume (VT) as the primary, and the specific binding part of the distribution volume (VS) as the secondary quantitative outcome measure of α4β2-nAChR availability. VS was determined by using a pseudo-reference region. Correlations between VT within relevant brain regions and Z-scores of five cognitive functions (episodic memory, executive function/working memory, attention, language, visuospatial function) were calculated. VT (and VS) were applied for between-group comparisons. Volume of interest and statistical parametric mapping analyses were carried out. Analyses revealed that in patients with mild Alzheimer's dementia compared to healthy controls, there was significantly lower VT, especially within the hippocampus, fronto-temporal cortices, and basal forebrain, which was similar to comparisons of VS. VT decline in Alzheimer's dementia was associated with distinct domains of impaired cognitive functioning, especially episodic memory and executive function/working memory. Using (-)-18F-flubatine PET in patients with mild Alzheimer's dementia, we show for the first time a cholinergic α4β2-nAChR deficiency mainly present within the basal forebrain-cortical and septohippocampal cholinergic projections and a relationship between lower α4β2-nAChR availability and impairment of distinct cognitive domains, notably episodic memory and executive function/working memory. This shows the potential of (-)-18F-flubatine as PET biomarker of cholinergic α4β2-nAChR dysfunction and specific cognitive decline. Thus, if validated by longitudinal PET studies, (-)-18F-flubatine might become a PET biomarker of progression of neurodegeneration in Alzheimer's dementia.

Memory Alteration Test to Detect Amnestic Mild Cognitive Impairment and Early Alzheimer's Dementia in Population with Low Educational Level.

Background/Aims: Short tests to early detection of the cognitive impairment are necessary in primary care setting, particularly in populations with low educational level. The aim of this study was to assess the performance of Memory Alteration Test (M@T) to discriminate controls, patients with amnestic Mild Cognitive Impairment (aMCI) and patients with early Alzheimer’s Dementia (AD) in a sample of individuals with low level of education.Methods: Cross-sectional study to assess the performance of the M@T (study test), compared to the neuropsychological evaluation (gold standard test) scores in 247 elderly subjects with low education level from Lima-Peru. The cognitive evaluation included three sequential stages: (1) screening (to detect cases with cognitive impairment); (2) nosological diagnosis (to determinate specific disease); and (3) classification (to differentiate disease subtypes). The subjects with negative results for all stages were considered as cognitively normal (controls). The test performance was assessed by means of area under the receiver operating characteristic (ROC) curve. We calculated validity measures (sensitivity, specificity and correctly classified percentage), the internal consistency (Cronbach’s alpha coefficient), and concurrent validity (Pearson’s ratio coefficient between the M@T and Clinical Dementia Rating (CDR) scores).Results: The Cronbach’s alpha coefficient was 0.79 and Pearson’s ratio coefficient was 0.79 (p < 0.01). The AUC of M@T to discriminate between early AD and aMCI was 99.60% (sensitivity = 100.00%, specificity = 97.53% and correctly classified = 98.41%) and to discriminate between aMCI and controls was 99.56% (sensitivity = 99.17%, specificity = 91.11%, and correctly classified = 96.99%).Conclusions: The M@T is a short test with a good performance to discriminate controls, aMCI and early AD in individuals with low level of education from urban settings.

DIFFERENTIAL EFFECT OF GLUCOSE METABOLISM AND INTRINSIC FUNCTIONAL CONNECTIVITY ON MEMORY PERFORMANCE OVER THE SPECTRUM OF ALZHEIMER'S DISEASE

While alterations in glucose metabolism are a well-established feature of Alzheimer's disease and linked to cognitive decline, aberrant patterns of spontaneous neural activity at rest are increasingly recognized as a characteristic of the disorder and are also evident in preclinical stages. The regional interrelationship of glucose consumption and resting-state activity and the differential contributions of these measures to memory function are still not well understood. The aim of the present study was to characterize this relationship and to assess the individual effects of the two modalities on memory function. Patients with subjective memory complaints (n=11), mild cognitive impairment (MCI) due to Alzheimer's disease (n=9), and early stage Alzheimer's dementia (n=10) were included in the analysis. We simultaneously acquired resting-state functional MRI (rs-fMRI) and [18F]fluorodeoxyglucose (FDG) PET data using a hybrid PET-MRI scanner. Independent component analysis was used to decompose rs-fMRI data into 75 spatially independent components of temporally synchronized neural activity. Using a combination of automated methods, we selected two default mode network components for the subsequent analysis. We performed voxel-wise regression analysis of intrinsic network connectivity and [18F]FDG uptake in the selected networks, correcting for voxelwise effects of gray matter volume. Mean values for both modalities were extracted from brain regions showing a significant effect of glucose consumption on intrinsic functional connectivity (p < 0.05 FWE-corrected) and entered into multiple regression models to estimate their effect on verbal memory performance (delayed recall of Logical Memory). Within the whole group, glucose uptake was significantly positively correlated with intrinsic connectivity in the ventral default mode network. Crucially, intrinsic connectivity but not glucose uptake predicted memory performance in patients with Alzheimer's disease (in the combined group of MCI and early stage dementia patients, as well in the early stage dementia group only). While glucose metabolism and intrinsic functional connectivity of resting state networks are closely interrelated, the disruption of functional connectivity in the default mode network better predicts memory performance. These results contribute to the development of rs-fMRI changes as a diagnostic marker and potential therapeutic target for Alzheimer's disease.

노래를 통한 초기 알츠하이머 치매환자의 자서전적 기억

노래를 통한 초기 알츠하이머 치매환자의 자서전적 기억

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer's Dementia.

Neurofibrillary pathology in Alzheimer's dementia (AD) is associated with cognitive impairments and cortical thinning, and begins in medial perirhinal cortex (mPRC) before entering entorhinal cortex (ERC). Thus, mPRC dysfunction (e.g., semantic object memory impairments) may predate or accompany ERC (i.e., episodic memory) dysfunction in the preclinical course of typical AD. We developed formulae estimating mPRC and ERC integrity (i.e., cortical thickness) using common neuropsychological tests in 31 healthy individuals and 58 early AD patients. These formulae estimated the longitudinal courses of mPRC and ERC functioning in independent groups of 28 optimally healthy individuals who developed AD (NC-AD) over 2.8-13.4 years and 28 pairwise-matched, stable, healthy individuals (NC-NC). Mixed models demonstrated significantly worse NC-AD than NC-NC estimated mPRC and ERC functioning at the earliest observation, 12 years preceding diagnosis, and a significant decline 4 years preceding the AD diagnosis. These findings demonstrate that specific neuropsychological impairments occur early in the course of preclinical AD and that tasks measuring mPRC functioning may serve as additional, powerful markers of preclinical AD.

Impact of the A2V Mutation on the Heterozygous and Homozygous Aβ1-40 Dimer Structures from Atomistic Simulations.

The A2V mutation was reported to protect from Alzheimer's disease in its heterozygous form and cause an early Alzheimer's disease type dementia in its homozygous form. Experiments showed that the aggregation rate follows the order A2V > WT (wild-type) > A2V-WT. To understand the impact of this mutation, we carried out replica exchange molecular dynamics simulations of Aβ1-40 WT-A2V and A2V-A2V dimers and compared to the WT dimer. Our atomistic simulations reveal that the mean secondary structure remains constant, but there are substantial differences in the intramolecular and intermolecular conformations upon single and double A2V mutation. Upon single mutation, the intrinsic disorder is reduced, the intermolecular potential energies are reduced, the population of intramolecular three-stranded β-sheets is increased, and the number of all α dimer topologies is decreased. Taken together, these results offer an explanation for the reduced aggregation rate of the Aβ1-40 A2V-WT peptides and the protective effect of A2V in heterozygotes.

A Study of Cortical Excitability, Central Motor Conduction, and Cortical Inhibition Using Single Pulse Transcranial Magnetic Stimulation in Patients with Early Frontotemporal and Alzheimer's Dementia.

Introduction:Degenerative cortical dementias affect several million people worldwide. Early diagnosis and categorization are essential for initiating appropriate pharmacological and nonpharmacological treatment so that deterioration can be postponed, and disability adjusted life years can be saved both for the patient and for the caregiver. Therefore, an early, simple, noninvasive biomarker will serve as a boon.Patients and Methods:Patients who satisfied probable Alzheimer's disease (AD) or frontotemporal dementia (FTD) using international consensus criteria for FTD and National Institute of Neurological Disorders and Stroke-AD and Related Disorders Association criteria for AD were evaluated using single pulse transcranial magnetic stimulation with figure of eight coil and motor evoked potential from right first dorsal interossei. Resting threshold (MT), central motor conduction time (CMCT), and silent period (SP) were evaluated.Results:Resting MT and SP are reduced in patients with Alzheimer's disease whereas CMCT is prolonged in patients with FTD and SP is in the lower limit of normal in both conditions.Conclusion:The patterns of central motor conduction and MT are distinctly different in patients with early Alzheimer's disease (AD) and FTD.

Cortical thinning of parahippocampal subregions in very early Alzheimer's disease

The stereotypical pattern of neurofibrillary tangle spreading in the earliest stages of typical Alzheimer's dementia (AD) predicts that medial perirhinal cortex (mPRC) atrophy precedes entorhinal cortex (ERC) atrophy, whereas the status of the parahippocampal cortex (PHC) remains unclear. Atrophy studies have focused on more advanced rather than early AD patients, and usually segment the entire PRC as opposed to the mPRC versus lateral PRC (lPRC). The present study therefore determined the extent of ERC, mPRC, lPRC, and PHC atrophy in very early AD (mean Mini-Mental State Examination score = 26) patients and its presumed prodrome amnestic mild cognitive impairment (mean Mini-Mental State Examination score = 28) compared to demographically matched controls. PHG structures were manually segmented (blinded rater) and cortical thicknesses extracted. ERC and mPRC were similarly atrophied in both patient groups. The lPRC was atrophied in the AD group only. Thus, atrophic changes in very early AD broadly map onto the pattern of neurofibrillary tangle spreading and suggest that mPRC, ERC, and lPRC, but not PHC-associated functional impairments, characterize very early-stage AD.

Association of the apolipoprotein E genotype with memory performance and executive functioning in cognitively intact elderly.

To test for a possible effect of the apolipoprotein E epsilon 4 (APOE ε4) allele on memory performance and executive functioning (EF) in cognitively intact elderly. The authors studied 202 randomly selected and cognitively intact older adults (65+ years) of the Leipzig Research Center for Civilization Diseases Health Care Study. Intact global cognitive functioning was defined using a Mini-Mental Status Examination (MMSE) score ≥ 28. Performance in memory was assessed with the CERAD Word List and Constructional Praxis Recall, performance in EF with the Trail Making Test Part B (TMT-B). Multivariable linear regressions were used to evaluate the association between cognitive performance and APOE status, controlled for covariates. Among the cognitively intact older adults, 21.3% (n = 43) were carriers of the APOE ε4 allele. Carriers did not differ significantly from noncarriers in terms of age, gender, intelligence level, or performance in memory but showed a significantly lower TMT-B performance as a measure of EF (TMT-B M time/SD = 105.6/36.2 vs. 91.9/32.7 s; Mann-Whitney U = 4,313.000; p = .009). The association between lower TMT-B performance and APOE ε4 genotype remained significant in multivariable linear regression analysis. Similar findings were found for the subsample of those 78 elderly, who reached a perfect MMSE-score of 30. A lower EF performance in cognitively intact older APOE ε4 allele carriers might be related to an early Alzheimer's dementia (AD) prodrome. In this case, a stronger focus on first subtle changes in EF may help to improve early AD detection in those being at genetic risk.