Verbal Episodic Memory Impairment Research Articles

Exploring language performance in people with mild cognitive impairment and Alzheimer's disease: a prospective longitudinal study

Background/Aims Language changes are the earliest signs and symptoms of mild cognitive impairment and Alzheimer's disease. The aim of this study was to explore the language difference performance between people with mild cognitive impairment, people with Alzheimer's disease and healthy individuals as a control group. To accomplish this aim, the language profile of both mild cognitive impairment and Alzheimer's disease needs to be characterised to determine which feature is more affected by both mild cognitive impairment and Alzheimer's disease among expressive language, receptive language, executive function and memory performance. Methods This case-control prospective study involved 90 participants. The Mini-Mental Status Examination and the Functional Assessment Staging Tool were used to classify the participants into three groups: people with mild cognitive impairment, people with Alzheimer's disease and healthy individuals as a control group. Then, the language performance of patients in the mild cognitive impairment and Alzheimer's disease groups was investigated and compared with those of the control group by using the Barnes Language Assessment. The groups were reassessed 6 months later to see if there was any change in language ability. Results The results showed that the mild cognitive impairment group and Alzheimer's disease group had significant decreases in expressive language (P>0.01), executive function (P>0.01), receptive language (P>0.01) and memory skills (P>0.01) from baseline to the reassessment at 6 months. Conclusions Language deficits, especially expressive language deficits, could appear before impairment in executive function, receptive language and verbal episodic memory in participants with mild cognitive impairment or Alzheimer's disease. Speech and language therapists can use the findings of this study to design and implement treatment programmes.

Normative data for the 12-item Buschke memory task in the Quebec-French population aged 50 and over

Objective The 12-item Buschke memory test is used to assess verbal episodic memory in adults and older adults. However, there is no normative data for this test adjusted to the older Quebec-French population. The aim of the study was to produce normative data for the 12-item Buschke for the Quebec-French population aged 50 and older. Method The normative sample consisted of 172 healthy French-speaking participants aged 50–89 years, from the Province of Quebec (Canada). The influence of age, years of formal education, and sex on five 12-item Buschke scores were analyzed. Based on the distribution of scores, normative data were developed as Z-scores equation, regression equation, and percentiles. Results Age, years of formal education, and sex were all associated with performance. Equations to calculate Z-scores were provided for the free recall trial 1 and the free recall trials 1–3. Stratified percentiles were provided for the delayed free recall and total recall 1–3. Conclusions The normative data for the 12-item Buschke improve the accuracy of clinicians to detect verbal episodic memory impairments in Quebec’s aging population.

Brain single cell transcriptomic profiles in episodic memory phenotypes associated with temporal lobe epilepsy

Memory dysfunction is prevalent in temporal lobe epilepsy (TLE), but little is known about the underlying molecular etiologies. Single-nucleus RNA sequencing technology was used to examine differences in cellular heterogeneity among left (language-dominant) temporal neocortical tissues from patients with TLE with (n = 4) or without (n = 2) impairment in verbal episodic memory. We observed marked cell heterogeneity between memory phenotypes and identified numerous differentially expressed genes across all brain cell types. The most notable differences were observed in glutamatergic (excitatory) and GABAergic (inhibitory) neurons with an overrepresentation of genes associated with long-term potentiation, long-term depression, and MAPK signaling, processes known to be essential for episodic memory formation.

Visual versus Verbal Working Memory in Statistically Determined Patients with Mild Cognitive Impairment: On behalf of the Consortium for Clinical and Epidemiological Neuropsychological Data Analysis (CENDA).

Previous research in mild cognitive impairment (MCI) suggests that visual episodic memory impairment may emerge before analogous verbal episodic memory impairment. The current study examined working memory (WM) test performance in MCI to assess whether patients present with greater visual versus verbal WM impairment. WM performance was also assessed in relation to hippocampal occupancy (HO), a ratio of hippocampal volume to ventricular dilation adjusted for demographic variables and intracranial volume. Jak etal. (2009) (The American Journal of Geriatric Psychiatry, 17, 368-375) and Edmonds, Delano-Wood, Galasko, Salmon, & Bondi (2015) (Journal of Alzheimer's Disease,47(1), 231-242) criteria classify patients into four groups: little to no cognitive impairment (non-MCI); subtle cognitive impairment (SCI); amnestic MCI (aMCI); and a combined mixed/dysexecutive MCI (mixed/dys MCI). WM was assessed using co-normed Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span Backwards and Wechsler Memory Scale-IV (WMS-IV) Symbol Span Z-scores. Between-group analyses found worse WMS-IV Symbol Span and WAIS-IV Digit Span Backwards performance for mixed/dys MCI compared to non-MCI patients. Within-group analyses found no differences for non-MCI patients; however, all other groups scored lower on WMS-IV Symbol Span than WAIS-IV Digit Span Backwards. Regression analysis with HO as the dependent variable was statistically significant for WMS-IV Symbol Span performance. WAIS-IV Digit Span Backwards performance failed to reach statistical significance. Worse WMS-IV Symbol Span performance was observed in patient groups with measurable neuropsychological impairment and better WMS-IV Symbol Span performance was associated with higher HO ratios. These results suggest that visual WM may be particularly sensitive to emergent illness compared to analogous verbal WM tests.

Early second‐line therapy is associated with improved episodic memory in anti‐NMDA receptor encephalitis

ObjectiveTo investigate whether the early administration of intravenous second‐line immunotherapy correlates with improved long‐term cognition and the potential mechanisms via imaging in adult patients with moderate‐to‐severe anti‐N‐methyl‐D‐aspartate (NMDA) receptor encephalitis.MethodsSixteen adult patients with moderate‐to‐severe anti‐NMDA receptor encephalitis past the acute stage and 15 healthy controls (HCs) performed a set of comprehensive neuropsychological tests, and underwent a resting‐state fMRI study to analyze resting state functional connectivity (FC). In addition, correlation analyses were performed between hippocampal FC and cognitive performance. All patients were received intravenous first‐line immunotherapy, and nine of them were also given intravenous second‐line immunotherapy within 3 months of disease onset.ResultsThe patients who only received first‐line immunotherapy showed significant verbal episodic memory impairments compared with HCs and those who received second‐line immunotherapy, while no significant differences were noted between the patients with second‐line immunotherapy and the HCs. In line with the results of neuropsychological tests, significant changes in bilateral hippocampal FC were observed in the patients who only received first‐line immunotherapy compared with both HCs and those who received second‐line immunotherapy. However, no significant differences in hippocampal FC were observed in the patients with second‐line immunotherapy compared with the HCs. Importantly, hippocampal‐medial prefrontal cortex (mPFC) connectivity positively correlated with memory performance.InterpretationIn the long term, early administration of intravenous second‐line immunotherapy may be associated with more favorable verbal episodic memory outcomes in patients with moderate‐to‐severe anti‐NMDA receptor encephalitis. These results may provide some evidence and guidance for the use of immunotherapy in this population.

Longitudinal Follow-Up of a Population with MCI: Predictive Value of the MIS Test with Delayed Recall for Progression to Dementia

Background: Early detection of dementia is currently of great interest and of crucial importance for the implementation of preventive measures and treatment of the disease. Impairment in verbal episodic memory, and in particular in a delayed recall phase, is considered one of the early markers of progression from mild cognitive impairment (MCI) to dementia. Therefore, having cognitive screening instruments with predictive value for progression is of utmost importance. Objective: The purpose of this work is to show the predictive value, sensitivity and specificity of the Memory Impairment Screen with delayed recall (MIS-DR) to predict conversion to dementia in patients with MCI. Methods: In retrospective study 502 patients over 60 years old, evaluated in the Older Adult Functional Evaluation Unit of our hospital for cognitive complaint, were diagnosed with MCI. They were followed up to assess conversion to dementia. Results: During follow up, 144 participants developed dementia (28.6%, 95% CI 24.76 - 32.85) and the average time of progression to dementia were 23 months (SD 13.2). The cut-off point was established below 6 for MIS-DR and it showed a sensitivity of 76% (95% CI 68.77 - 77.84) and a specificity of 56% (95% CI 50.44 - 61.58), with a positive predictive value of 41% (95% CI 34.78 - 47.6) and a negative predictive value of 85% (95% CI 80.53 - 91.11) for predicting progression to dementia. Of those patients who obtained a MIS-DR score below 6, 41% developed dementia, in contrast to 14.53% of those with a score above or equal to 6, OR 4.09 (95% CI 2.64 - 6.34), p < 0.00001. There were no significant differences in terms of gender, education level or vascular risk factors among patients who converted and those who did not convert to dementia. Conclusion: We believe that MIS-DR is a useful and valid test to detect episodic memory impairment and to identify patients at risk of progression to dementia.

Personality factors and cognitive functioning in elderly with Parkinson's disease.

ABSTRACTParkinson's disease (PD) is a chronic and progressive neurological disease, resulting from cell degeneration in the substantia nigra, responsible for the production of dopamine.Objective: This study aimed to characterize the cognitive functioning, personality factors and prevalence of depressive and anxiety symptoms in individuals with Parkinson's disease (PD). Furthermore, this study sought to analyze whether personality factors were predictors of cognitive functioning.Methods: The sample consisted of 30 elderly with PD. Participants completed a sociodemographic data sheet, the NEO-FFI-R (Five Factor Inventory NEO Revised), the Montreal Cognitive Assessment, the Beta-III, the phonemic verbal fluency test and semantics (Animals), the digits span subtest of the Wechsler Intelligence Scale for Adults and the Boston Naming Test and the word list of the CERAD battery, the Geriatric Depression Scale and the Beck Anxiety Inventory. Results: The elderly with PD presented impairment in verbal episodic memory and executive functions. Most of the participants demonstrated low levels of neuroticism. The extraversion factor was positively correlated with executive functions and the openness to experience factor was positively correlated with verbal episodic memory. It was concluded that the elderly with PD presented memory and executive function impairments. The factor that most contributed to performance of the elderly with PD on memory and executive function tasks was the extraversion factor.

Verbal episodic memory profiles in HIV-Associated Neurocognitive Disorders (HAND): A comparison with Huntington's disease and mesial temporal lobe epilepsy

ABSTRACTHIV-associated neurocognitive disorders (HAND) commonly feature verbal episodic memory impairment historically characterized by a retrieval deficit, consistent with a classic “subcortical” presentation; however, there are hints of a subtle shift toward a more “cortical” memory profile characterized by a primary encoding deficit. The current study evaluated this possibility by comparing the pattern of HAND-associated verbal episodic memory deficits to those of traditional “subcortical” (i.e., Huntington’s disease; HD) versus “cortical” (i.e., left temporal lobe epilepsy with mesial temporal sclerosis; L-MTLE) profiles. Seventy-seven individuals with HAND, 47 individuals with HD, 21 individuals with L-MTLE, and 45 healthy participants were administered the California Verbal Learning Test - 2nd Edition (CVLT-II). CVLT-II profiles were classified as reflecting a primary encoding deficit, retrieval deficit, or a normal profile. Among participants with a deficit profile, the HAND group showed the highest rates of retrieval versus encoding profiles (71% vs. 29%), followed by HD (59% vs. 41%), L-MTLE (46% vs. 54%), and healthy (50% vs. 50%) groups. While significant profile heterogeneity was observed across clinical groups, findings suggest that HIV-associated verbal episodic memory impairments are most consistent with a traditional “subcortical,” retrieval deficit profile, consistent with the primary frontostriatal neuropathogenesis of HIV disease.

Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder

The effects of alcoholism on cognitive and motor functioning are heterogeneous. While the role of some factors (patterns of alcohol consumption, eating habits or associated liver disease) has been hypothesized, the origins of this heterogeneity remain difficult to establish. The goals of the present study were thus to identify the clinical and biological risk factors for alcohol-related neuropsychological impairments and to determine the threshold beyond which these risk factors can be considered significant. Thirty alcoholic patients and 15 healthy controls had a blood test and underwent a neuropsychological examination. Alcohol severity measures, and liver, thiamine and malnutrition variables, were included in logistic regression models to determine the risk factors for cognitive and motor impairments (executive functions, visuospatial abilities, verbal episodic memory, ataxia), as well as those related to the severity of patients’ overall neuropsychological profile (moderate or severe impairments). Liver fibrosis was found to be a risk factor for executive impairments and also for ataxia, when it was associated with long-term alcohol misuse and symptoms of withdrawal. Altered thiamine metabolism was solely predictive of verbal episodic memory impairments. This combination of biological abnormalities was associated with a profile of moderate neuropsychological impairments. Malnutrition was associated with a profile of more severe impairments. Malnutrition, altered liver function and thiamine metabolism explain, at least partially, the heterogeneity of alcohol-related neuropsychological impairments. Our findings could allow clinicians to identify patients at particular risk of severe neuropsychological impairments before the onset of irreversible and debilitating neurological complications.

Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies

Objective: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. Methods: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions: Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB.

Les troubles mnésiques dans les gliomes temporaux gauches

Episodic memory disorders are frequent in patients with temporal lesion. Verbal or visuo-spatial memory disorders depend on the location and the lateralization of the lesion. These disorders are well described in temporal epilepsy but rarely in population with cerebral tumor and especially not specifically focus on temporal glioma. The purpose of this study was to describe neuropsychological examination in patient with temporal glioma in the database of the regional memory centre of Besançon. Four patients were identified (all right-handed and with a left temporal glioma). Verbal episodic memory impairment and auditory-verbal short-term memory impairment were observed. One patient had also visual memory disorders. Therefore, further investigations showed an associated Alzheimer's disease. This finding modified the clinical management of this patient. Extensive neuropsychological assessment should be systematic initially to seek an associated pathology, especially in elderly patients, if the cognitive profile is unusual, during the follow-up to better understand cognitive evolution and the effect of therapies on cognition.

“I know your name, but not your number” – Patients with verbal short-term memory deficits are impaired in learning sequences of digits

Studies on verbal learning in patients with impaired verbal short-term memory (vSTM) have revealed dissociations among types of verbal information. Patients with impaired vSTM are able to learn lists of known words but fail to acquire new word forms. This suggests that vSTM is involved in new word learning. The present study assessed both new word learning and the learning of digit sequences in two patients with impaired vSTM. In two experiments, participants were required to learn people's names, ages and professions, or their four digit ‘phone numbers’. The STM patients were impaired on learning unknown family names and phone numbers, but managed to acquire other verbal information. In contrast, a patient with a severe verbal episodic memory impairment was impaired across information types. These results indicate verbal STM involvement in the learning of digit sequences.

Similar verbal memory impairments in schizophrenia and healthy aging. Implications for understanding of neural mechanisms

Memory is impaired in schizophrenia patients but it is not clear whether this is specific to the illness and whether different types of memory (verbal and nonverbal) or memories in different cognitive domains (executive, object recognition) are similarly affected. To study relationships between memory impairments and schizophrenia we compared memory functions in 77 schizophrenia patients, 58 elderly healthy individuals and 41 young healthy individuals. Tests included verbal associative and logical memory and memory in executive and object recognition domains. We compared relationships of memory functions to each other and to other cognitive functions including psychomotor speed and verbal and spatial working memory. Compared to the young healthy group, schizophrenia patients and elderly healthy individuals showed similar severe impairment in logical memory and in the ability to learn new associations (NAL), and similar but less severe impairment in spatial working memory and executive and object memory. Verbal working memory was significantly more impaired in schizophrenia patients than in the healthy elderly. Verbal episodic memory impairment in schizophrenia may share common mechanisms with similar impairment in healthy aging. Impairment in verbal working memory in contrast may reflect mechanisms specific to schizophrenia. Study of verbal explicit memory impairment tapped by the NAL index may advance understanding of abnormal hippocampus dependent mechanisms common to schizophrenia and aging.

Abnormal Long-Term Episodic Memory Profiles in Multiple Sclerosis?

Objective: Various verbal episodic memory impairments have been demonstrated in multiple sclerosis (MS), including encoding, retrieval and storage processes. Our clinical experiment suggests that a subset of MS patients may show another pattern with a distinctive evolution of performances after a 20 minutes delay (short-delay versus long-delay free recall). Methods: The current study assessed performances on the California Verbal Learning Test (CVLT) in MS with a special focus on evolution after delay to identify a subgroup of patients who may show a significant spontaneous improvement of long-delay free recall in comparison with short-delay free recall. Data from 52 MS patients were compared with those from 32 controls. Group analyses were conducted on classical scores. Individual MS performances were also analyzed, according to confidence intervals calculated using control data. Results: From individual analysis, memory comorbidities were frequently observed in a MS patient (17% of MS patients had only one impaired score, 17% had two or three scores, 27% had four or five scores and 38% had six or more). Regarding the evolution after delay, three profiles were highlighted: two classical (stable and worsening, i.e. storage deficit) and a third showing a significant degree of improvement. The improvement was significantly correlated with processing speed, primacy effect and sensitivity to retroactive interference only in this third MS subgroup. This benefit from delay was not related to the effect of semantic clustering. Conclusion: The current study suggests that a subgroup of MS patients might present a previously unreported abnormal long-term memory profile, in which an impaired short-term performance contrasts with a significant spontaneous improvement with delay. Previous studies have demonstrated the relevance of spaced learning in MS rehabilitation. If our results are corroborated in a larger sample, the CVLT may help to select patients that are likely to benefit from this temporal memory care.

Tip-of-the-tongue for proper names in non-amnestic mild cognitive impairment

Abstract Difficulty in recalling people's names is very common in the early stages of Alzheimer's disease and in mild cognitive impairment (MCI). Recent studies using tip-of-the-tongue (TOT) tasks have shown that impaired naming of famous people by amnestic MCI patients is associated with difficulties in accessing the phonological representations of the names, but not with semantic breakdown. The aims of the present study were to investigate, by use of a TOT task, semantic and phonological access to famous people's names in non-amnestic MCI and to test whether impairment in verbal episodic memory and other cognitive domains leads to difficulties in semantic and phonological access. We compared the performance of individuals with multiple domain amnestic MCI with that of individuals with multiple domain non-amnestic MCI and of healthy controls, and we studied the relationships between TOT production and the functioning of verbal episodic memory and other cognitive domains. In the multiple domain MCI groups (amnestic and non-amnestic), the main process affected was phonological access; failure in phonological access was related to deficits in general cognitive functioning and executive functioning. Semantic access was not impaired in either type of MCI. We interpret the findings in light of the transmission deficit hypothesis, as multiple domain MCI involves greater deficit in transmission from semantic to phonological representations than that produced by normal ageing, possibly because of reductions in cognitive resources and executive functions.

Right Temporal Lobe Atrophy: A Neuropsychological and Functional Imagery Study (P03.083)

Objective: This study aimed to clarify the specific neuropsychological and behavioural profile associated with right temporal lobe atrophy (RTLA) and to correlate cerebral hypoperfusion with cognitive and emotional impairments in RTLA patients. Background Clinical data about Right Temporal Lobe Atrophy are relatively limited in the neuropsychological literature. However, this kind of focal atrophy, which occuring in a context of a neurodegenerative disease, seems to have a specific clinical profile. Some authors reported the prevalence of verbal and non-verbal episodic memory impairment, topographical disorientation, progressive prosopagnosia and deterioration of semantic knowledge about famous people (Chan et al. 2009 ; Josephs et al. 2009 ; Gorno-Tempini et al. 2004). Design/Methods: Fourteen patients (five women, and nine men, mean aged 61.1 range=39 to 74), with RTLA on brain MRI, were compared to fourteen control subjects matched for age and sex. Several neuropsychological tests were administrated to patients and behaviour was assessed with questionnaire to participants and caregivers. Besides the patients had ethylcysteinate dimer (ECD) SPECT imagery. Brain perfusion will be correlated to cognitive data using Voxel Based Morphometry (VBM) analysis (with Matlab 7.7 software, SPM5). Results: Our first results showed a deficit in visual recognition memory and a mild impairment in verbal episodic memory. Specific semantic knowledge about famous people was severely impaired, whereas general semantic knowledge was relatively spared. Language, visuo-perceptive and visuo-spatial skills and executive functions were well preserved. RTLA patients were impaired at recognizing emotions from faces, especially fear and disgust. Finally, many patients suffered from depression to the beginning of the disease. Others behavioural manifestations were observed in some patients (apathy, impulsivity, disinhibition, anxiety etc.). At time, SPECT imagery is ongoing for the patients and correlations with perfusion will be presented during the congress. Conclusions: This study will objective the neuropsychological impairments associated with RTLA and precise their brain localization. Disclosure: Dr. Longato has nothing to disclose. Dr. Jung has nothing to disclose. Dr. Noblet has nothing to disclose. Dr. Ehrhardt has nothing to disclose. Dr. Philippi has nothing to disclose. Dr. Hubele has nothing to disclose. Dr. Namer has nothing to disclose. Dr. Blanc has received personal compensation for activities with Biogen Idec, Novartis, Jassens-Cilag,Eisai compensation Bayer Schering Pharma, Teva, Merck, and Sanofi as a consultant, speaker or scientific advisory board member.

Verbal episodic memory in 426 multiple sclerosis patients: impairment in encoding, retrieval or both?

Episodic memory is frequently impaired in multiple sclerosis (MS) patients but the exact nature of the disorder is controversial. It was initially thought to be due to a retrieval deficit but some studies have demonstrated an encoding deficit, which could be linked to a slowing of information processing speed or to a deficit in elaboration of strategies. The main objective of this study is to assess the prevalence and the nature of verbal episodic memory (VEM) impairment in MS patients. We retrieved memory performances of 426 patients [314 F-112 M; mean age: 46.1 years; median Expanded Disability Status Scale (EDSS) score: 3.1] from a neuropsychological data base. VEM was assessed using the 16 words RL-RI 16 test. 66% MS patients present at least one recall impaired in VEM (37.2% from 2 to 5 recall). 14.2% MS patients present an impairment in encoding phase. We observed that 5% of patients presented recognition difficulties. Correlations were observed between VEM performances and EDSS, and disease duration but no group effect (ANOVA) is observed between form of MS and VEM performances. These results confirm the high prevalence of VEM impairment in MS patients. Deficits affect mainly information retrieval in early stage MS patients and are then linked to encoding as disability increases. Storage disorders are infrequent, so cognitive rehabilitation with mental imaging could be effective in MS patients.

P41 Cognitive dysfunction in hospitalised patients prior to discharge following acute exacerbation of COPD

RationaleCognitive impairment is one of the least well-studied COPD comorbidities. It occurs in a proportion of hypoxemic patients, but its presence during acute exacerbation has not been established. We assessed...

Neural bases of verbal episodic memory impairment in behavioural variant FTD and early onset Alzheimer's disease: a 99m Tc-HMPAO-SPEC-T study

Neural bases of verbal episodic memory impairment in behavioural variant FTD and early onset Alzheimer's disease: a 99m Tc-HMPAO-SPEC-T study

Neuropsychological and neurobiological markers of the preclinical stage of Alzheimer’s disease.

Dementia, especially Alzheimer's disease, has a high prevalence in the elderly population. Therefore, identifying individuals who are at a high risk for early diagnosis is crucial to allow both pharmacological and behavioral therapeutic interventions, which in some cases can delay the progression of dementia. This paper describes neuropsychological and neurobiological markers for the early diagnosis of Alzheimer's disease and presents the main risk factors, including neuropathological, neuroanatomical, neurofunctional, genetic, and neuropsychological. The literature shows that the combination of these markers is the best method for predicting Alzheimer's disease, years before its clinical manifestation. The most prevalent neurobiological and neuropsychological risk factors include (1) senile plaques and neurofibrillary tangles in the medial temporal lobe and cortical regions, (2) low concentrations of Aβ1-42 peptide and high concentrations of total tau protein and phosphorylated tau protein in cerebrospinal fluid, (3) reduced global cerebral volume, increased ventricular volume, and atrophy in the hippocampal formation and entorhinal cortex, (4) global reductions in cerebral metabolism and perfusion in the temporoparietal junction, temporal, parietal, and frontal lobes, hippocampal formation, and posterior cingulate cortex, (5) the presence of the apolipoprotein E e4 allele, and (6) verbal anterograde episodic long-term memory impairment and executive dysfunction. The present review discusses the evidence for markers that identify individuals who are at a high risk of developing Alzheimer's disease and the importance of longitudinal studies in this context.