Cognitive deficits and course of recovery in transient global amnesia: a systematic review.

OBJECTIVE: Published evidence suggests that cognitive impairment during a TGA (transient global amnesia) spell may not be confined to episodic memory. We undertook a systematic review to determine the pattern of cognitive deficits during a TGA episode. As a secondary objective, we aimed to delineate the course of cognitive recovery. METHODS: MEDLINE, EMBASE, CENTRAL, and Google scholar were systematically searched up to October 2023. Observational controlled studies including 10 or more TGA patients (Hodges and Warlow criteria) were retrieved. Data from case-control, cross-sectional, and cohort studies were reviewed and qualitatively synthesized. RESULTS: Literature search yielded 1302 articles. After the screening of titles and abstracts, 115 full texts were retrieved and 17 of them were included in the present systematic review. During the acute phase, spatiotemporal disorientation, dense anterograde and variable retrograde amnesia, semantic memory retrieval difficulties, and working memory deficits comprised the neuropsychological profile of patients with TGA. Visuospatial abilities, attention and psychomotor speed, semantic memory, confrontation naming, and other measures of executive function (apart from semantic fluency and working memory) were consistently found normal. In the course of recovery, after the resolution of repetitive questioning, the restoration of spatiotemporal orientation follows, working memory and semantic memory retrieval ensue, while episodic memory impairment persists for longer. Meticulous evaluations may reveal subtle residual memory (especially recognition) deficits even after 24 h. CONCLUSIONS: Μemory impairment, spatiotemporal disorientation, and working memory deficits constitute the pattern of cognitive impairment during a TGA spell. Residual memory deficits may persist even after 24 h.

The impact of genetic factors on the response to migraine therapy.

Migraine is a multidimensional disease affecting a large portion of the human population presenting with a variety of symptoms. In the era of personalized medicine, successful migraine treatment presents a challenge, as several studies have shown the impact of a patient's genetic profile on therapy response. However, with the emergence of contemporary treatment options, there is promise for improved outcomes. A literature search was conducted in PubMed and Scopus, in order to obtain studies investigating the impact of genetic factors on migraine therapy outcome. Overall, 23 studies were included in the current review, exhibiting diversity in the treatments used and the genetic variants investigated. Divergent genes were assessed for each category of migraine treatment. Several genetic factors were identified to contribute to the heterogeneous response to treatment. SNPs related to pharmacodynamic receptors, pharmacogenetics and migraine susceptibility loci were the most investigated variants, revealing some interesting significant results. To date, various associations have been recorded correlating the impact of genetic factors on migraine treatment responses. More extensive research needs to take place with the aim of shedding light on the labyrinthine effects of genetic variations on migraine treatment, and, consequently, these findings can promptly affect migraine treatment and improve migraine patients' life quality in the vision of precise medicine.

Neurocognitive Impairment in Long COVID: A Systematic Review.

OBJECTIVE: Although Coronavirus disease 2019 (COVID-19) is primarily a respiratory infectious disease, it has also been associated with a wide range of other clinical manifestations. It is widely accepted in the scientific community that many patients after recovery continue to experience COVID-19-related symptoms, including cognitive impairment. The aim of this systematic review was to investigate the cognitive profile of patients with long-COVID syndrome. METHODS: A systematic search of empirical studies was conducted through the PubMed/Medline and Scopus electronic databases. Cross-sectional and longitudinal studies published between 2020 and 2023 were included. RESULTS: Of the 516 studies assessed for eligibility, 36 studies met the inclusion criteria. All included studies support the presence of persistent cognitive changes after COVID-19 disease. Executive function, memory, attention, and processing speed appear to be the cognitive domains that are predominantly associated with long-COVID syndrome, whereas language is an area that has not been sufficiently investigated. CONCLUSIONS: In this review, the high frequency of cognitive impairment after COVID-19 is evident. If we consider that cognitive functioning affects our ability to live independently and is a key determinant of our quality of life, it is imperative to precisely define those factors that may induce cognitive impairment in COVID-19 survivors, with the ultimate goal of early diagnosis of cognitive changes and, consequently, the development of targeted rehabilitation interventions to address them.

Cognitive trajectories preluding the onset of different dementia entities: a descriptive longitudinal study using the NACC database.

OBJECTIVE: To describe the 10-year preclinical cognitive trajectories of older, non-demented individuals towards the onset of the four most prevalent types of dementia, i.e., Alzheimer's disease(AD), Lewy body(LBD), vascular(VD) and frontotemporal dementia(FTD). METHODS: Our analysis focused on data from older (≥ 60years) NACC (National Alzheimer's Coordinating Center) participants. Four distinct presymptomatic dementia groups (AD-LBD-VD-FTD) and a comparison group of cognitively unimpaired(CU) participants were formed. Comprehensive cognitive assessments involving verbal episodic memory, semantic verbal fluency, confrontation naming, mental processing speed - attention and executive function - cognitive flexibility were conducted at baseline and on an approximately yearly basis. Descriptive analyses (adjusted general linear models) were performed to determine and compare the yearly cognitive scores of each group throughout the follow-up. Exploratory analyses were conducted to estimate the rates of cognitive decline. RESULTS: There were 3343 participants who developed AD, 247 LBD, 108 FTD, 155 VD and 3398 composed the CU group. Participants with AD performed worse on episodic memory than those with VD and LBD for about 3 to 4 years prior to dementia onset (the FTD group documented an intermediate course). Presymptomatic verbal fluency and confrontation naming trajectories differentiated quite well between the FTD group and the remaining dementia entities. Participants with incident LBD and VD performed worse than those with AD on executive functions and mental processing speed-attention since about 5 years prior to the onset of dementia, and worse than those with FTD more proximally to the diagnosis of the disorder. CONCLUSIONS: Heterogeneous cognitive trajectories characterize the presymptomatic courses of the most prevalent dementia entities.

Neuropsychiatric symptoms and white matter hyperintensities in older adults without dementia.

OBJECTIVE: We aimed to examine associations between neuropsychiatric symptoms (NPS) and white matter hyperintensities (WMH) status in older adults without dementia under the hypothesis that WMH increased the odds of having NPS. DESIGN: Longitudinal analysis of data acquired from the National Alzheimer's Coordinating Center Uniform Data Set. SETTINGS: Data were derived from 46 National Institute on Aging - funded Alzheimer's Disease Research Centers. PARTICIPANTS: NACC participants aged ≥50 years with available data on WMH severity with a diagnosis of mild cognitive impairment (MCI) or who were cognitively unimpaired (CU) were studied. Among 4617 CU participants, 376 had moderate and 54 extensive WMH. Among 3170 participants with MCI, 471 had moderate and 88 had extensive WMH. MEASUREMENTS: Using Cardiovascular Health Study (CHS) scores, WMH were coded as no to mild (CHS score: 0-4), moderate (score: 5-6) or extensive (score: 7-8). NPS were quantified on the Neuropsychiatric Inventory Questionnaire. Binary logistic regression models estimated the odds of reporting each of 12 NPS by WMH status separately for individuals with MCI or who were CU. RESULTS: Compared to CU individuals with no to mild WMH, the odds of having elation [9.87, (2.63-37.10)], disinhibition [4.42, (1.28-15.32)], agitation [3.51, (1.29-9.54)] or anxiety [2.74, (1.28-5.88)] were higher for the extensive WMH group, whereas the odds of having disinhibition were higher for the moderate WMH group [1.94, (1.05-3.61)]. In the MCI group, he odds of NPS did not vary by WMH status. CONCLUSIONS: Extensive WMH were associated with higher odds of NPS in CU older adults but not in those with MCI.

Language and Communication Interventions in People with Alzheimer's Disease: A Systematic Review.

Although language impairment is frequently observed in patients with Alzheimer's disease (pwAD), targeted language rehabilitation is often overlooked. The present study reviews published evidence on the impact of language training, either alone or in combination with cognitive training, on cognitive outcomes in pwAD. A systematic search of PubMed, Google Scholar, and Cochrane was carried out, including studies published from inception to November 2023. A total of eight research articles (four randomized controlled trials and four observational studies) met the inclusion criteria: six assessed language training combined with cognitive training and two evaluated language rehabilitation alone. Regarding language and non-language (mainly memory, attention, and executive functions) outcomes, there was a consensus among studies that language rehabilitation (alone or in combination with cognitive training) yields positive results. Some of the articles also explored the impact on patients' and their caregivers' quality of life, with all but one showing improvement. Consequently, the combination of language and cognitive training leads to improvements across various cognitive domains. However, limited evidence supports the value of sole language rehabilitation. This conclusion is influenced by heterogeneity among studies (different types and duration of interventions, small participant sets, various assessment tools), and, thus, further research is warranted.

Neurocognitive Impairment and Social Cognition in Parkinson's Disease Patients.

In addition to motor symptoms, neurocognitive impairment (NCI) affects patients with prodromal Parkinson's disease (PD). NCI in PD ranges from subjective cognitive complaints to dementia. The purpose of this review is to present the available evidence of NCI in PD and highlight the heterogeneity of NCI phenotypes as well as the range of factors that contribute to NCI onset and progression. A review of publications related to NCI in PD up to March 2023 was performed using PubMed/Medline. There is an interconnection between the neurocognitive and motor symptoms of the disease, suggesting a common underlying pathophysiology as well as an interconnection between NCI and non-motor symptoms, such as mood disorders, which may contribute to confounding NCI. Motor and non-motor symptom evaluation could be used prognostically for NCI onset and progression in combination with imaging, laboratory, and genetic data. Additionally, the implications of NCI on the social cognition of afflicted patients warrant its prompt management. The etiology of NCI onset and its progression in PD is multifactorial and its effects are equally grave as the motor effects. This review highlights the importance of the prompt identification of subjective cognitive complaints in PD patients and NCI management.

Longitudinal Cognitive Trajectories in Older Adults with Restless Legs Syndrome or Willis-Ekbom Disease.

Background: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) has occasionally but not consistently been associated with cognitive and most notably language and executive impairment. The present study was conducted to investigate the cognitive trajectories of older individuals with RLS/WED. Methods: Participants were drawn from the randomly selected, older (>64 years), population-based HELIAD cohort. Individuals without dementia and with available neuropsychological evaluations at baseline and follow-up were considered for potential eligibility. A comprehensive assessment examining five principal components of cognition (memory, visuo-spatial ability, attention, executive function, and language) was administered to the participants. Generalized estimating equation analyses were used to examine the unadjusted and adjusted (for critical factors and covariates) effects of RLS/WED on cognition over time. Results: A total of 1003 predominantly female (59.5%), older (72.9 ± 4.9 years) participants with follow-up evaluations after a mean of 3.09 ± 0.85 years and without dementia at baseline and follow-up were included in the present study. Among them, 81 were diagnosed with RLS/WED at baseline. Global cognition, memory, attention, and executive and visuo-perceptual skills did not differ between those with and without RLS/WED. However, the RLS/WED group performed worse on language at baseline by a standard deviation of 0.249, while demonstrating a mitigated language decline over time, by a standard deviation of 0.063. The unadjusted models yielded similar results. Conclusions: Our findings were indicative of a baseline language disadvantage among older individuals with RLS/WED, but the initial discrepancy tends to dissolve over time.

The Contribution of Functional Near-Infrared Spectroscopy (fNIRS) to the Study of Neurodegenerative Disorders: A Narrative Review.

Functional near-infrared spectroscopy (fNIRS) is an innovative neuroimaging method that offers several advantages over other commonly used modalities. This narrative review investigated the potential contribution of this method to the study of neurodegenerative disorders. Thirty-four studies involving patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), frontotemporal dementia (FTD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) and healthy controls were reviewed. Overall, it was revealed that the prefrontal cortex of individuals with MCI may engage compensatory mechanisms to support declining brain functions. A rightward shift was suggested to compensate for the loss of the left prefrontal capacity in the course of cognitive decline. In parallel, some studies reported the failure of compensatory mechanisms in MCI and early AD; this lack of appropriate hemodynamic responses may serve as an early biomarker of neurodegeneration. One article assessing FTD demonstrated a heterogeneous cortical activation pattern compared to AD, indicating that fNIRS may contribute to the challenging distinction of these conditions. Regarding PD, there was evidence that cognitive resources (especially executive function) were recruited to compensate for locomotor impairments. As for ALS, fNIRS data support the involvement of extra-motor networks in ALS, even in the absence of measurable cognitive impairment.

Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review.

In this narrative review, we delved into the intricate interplay between Apolipoprotein E (APOE) alleles (typically associated with Alzheimer's disease-AD) and alpha-synucleinopathies (aS-pathies), involving Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple-system atrophy (MSA). First, in-vitro, animal, and human-based data on the exacerbating effect of APOE4 on LB pathology were summarized. We found robust evidence that APOE4 carriage constitutes a risk factor for PDD-APOE2, and APOE3 may not alter the risk of developing PDD. We confirmed that APOE4 copies confer an increased hazard towards DLB, as well. Again APOE2 and APOE3 appear unrelated to the risk of conversion. Of note, in individuals with DLB APOE4, carriage appears to be intermediately prevalent between AD and PDD-PD (AD > DLB > PDD > PD). Less consistency existed when it came to PD; APOE-PD associations tended to be markedly modified by ethnicity. Finally, we failed to establish an association between the APOE gene and MSA. Phenotypic associations (age of disease onset, survival, cognitive-neuropsychiatric- motor-, and sleep-related manifestations) between APOE alleles, and each of the aforementioned conditions were also outlined. Finally, a synopsis of literature gaps was provided followed by suggestions for future research.

Exploring Verbal Fluency Strategies among Individuals with Normal Cognition, Amnestic and Non-Amnestic Mild Cognitive Impairment, and Alzheimer's Disease.

Background and Objectives: The present study explored the utilization of verbal fluency (VF) cognitive strategies, including clustering, switching, intrusions, and perseverations, within both semantic (SVF) and phonemic (PVF) conditions, across a continuum of neurocognitive decline, spanning from normal cognitive ageing (NC) to mild cognitive impairment (MCI) and its subtypes, amnestic (aMCI) and non-amnestic (naMCI), as well as AD. Materials and Methods: The study sample was derived from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. The sample included 1607 NC individuals, 146 with aMCI (46 single-domain and 100 multi-domain), 92 with naMCI (41 single-domain and 51 multi-domain), and 79 with AD. Statistical analyses, adjusting for sex, age, and education, employed multivariate general linear models to probe differences among these groups. Results: Results showed that AD patients exhibited poorer performance in switching in both VF tasks and SVF clustering compared to NC. Similarly, the aMCI group performed worse than the NC in switching and clustering in both tasks, with aMCI performing similarly to AD, except for SVF switching. In contrast, the naMCI subgroup performed similarly to those with NC across most strategies, surpassing AD patients. Notably, the aMCI subgroup's poor performance in SVF switching was mainly due to the subpar performance of the multi-domain aMCI subgroup. This subgroup was outperformed in switching in both VF tasks by the single-domain naMCI, who also performed better than the multi-domain naMCI in SVF switching. No significant differences emerged in terms of perseverations and intrusions. Conclusions: Overall, these findings suggest a continuum of declining switching ability in the SVF task, with NC surpassing both aMCI and AD, and aMCI outperforming those with AD. The challenges in SVF switching suggest executive function impairment associated with multi-domain MCI, particularly driven by the multi-domain aMCI.

Objective Physical Function in the Alzheimer's Disease Continuum: Association with Cerebrospinal Fluid Biomarkers in the ALBION Study.

Cognitive and physical decline, both indicators of aging, seem to be associated with each other. The aim of the present study was to investigate whether physical function parameters (walking time and handgrip strength) are related to cerebrospinal fluid (CSF) biomarkers (amyloid-beta Aß42, Tau, PhTau) in individuals in the Alzheimer's disease (AD) continuum. The sample was drawn from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study, comprising 163 individuals aged 40-75 years: 112 cognitively normal (CN) and 51 with mild cognitive impairment (MCI). Physical function parameters were measured at baseline, a lumbar puncture was performed the same day and CSF biomarkers were analyzed using automated methods. The association between walking time, handgrip strength and CSF biomarkers was evaluated by linear correlation, followed by multivariate linear regression models adjusted for age, sex, education and APOEe4 genotype. Walking time was inversely related to CSF Aß42 (lower CSF values correspond to increased brain deposition) in all participants (p < 0.05). Subgroup analysis showed that this association was stronger in individuals with MCI and participants older than 60 years old, a result which remained statistically significant after adjustment for the aforementioned confounding factors. These findings may open new perspectives regarding the role of mobility in the AD continuum.

Lack of Association between CD33 rs3865444 and Amyotrophic Lateral Sclerosis: A Case-Control Study.

BACKGROUND: Microglial activation is considered to assume a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). To date, the relationship between ALS and the rs3865444 polymorphism of the cluster of differentiation 33 (CD33) has not been explored. The current report aimed to investigate the potential connection between CD33 rs3865444 and ALS. METHODS: Patients diagnosed with sporadic ALS according to the revised El Escorial criteria, as well as age and sex matched community controls, were enrolled. Two evenly numbered, age and sex matched groups of 155 participants each were genotyped. RESULTS: No association was found between rs3865444 and ALS [log-additive odds ratio (OR) = 0.83 (0.57, 1.22), over-dominant OR = 0.86 (0.55, 1.36), recessive OR = 0.73 (0.25, 2.17), dominant OR = 0.82 (0.52, 1.29), co-dominant OR1 = 0.68 (0.23, 2.05) and co-dominant OR2 = 0.84 (0.53, 1.33)]. Moreover, no relationship was established between rs3865444 and the age of ALS onset based on both unadjusted and sex adjusted Cox-proportional hazards models. Finally, no association between rs3865444 and ALS was found in subgroup analyses based on the site of ALS onset (bulbar or spinal) and sex. CONCLUSIONS: The current analysis is the first to report that rs3865444 is not linked to ALS. Larger multi-racial studies are required to confirm these findings.

Pesticides and tremor: An overview of association, mechanisms and confounders.

Pesticides are a heterogeneous class of chemicals mainly used for the protection of crops from pests. Because of their very widespread use, acute or/and chronic exposure to these chemicals can lead to a plethora of sequelae inflicting diseases, many of which involve the nervous system. Tremor has been associated with pesticide exposure in human and animal studies. This review is aimed at assessing the studies currently available on the association between the various types of pesticides/insecticides and tremor, while also accounting for potential confounding factors. To our knowledge, this is the first coherent review on the subject. After appraising the available evidence, we call for more intensive research on this topic, as well as intonate the need of implementing future preventive measures to protect the exposed populations and to reduce potential disabilities and social drawbacks.

Longitudinal episodic memory trajectories in older adults with normal cognition.

OBJECTIVE: To determine the longitudinal trajectories and normative standards of episodic memory in older adults. METHODS: Participants were drawn from the cognitively normal(CN) subgroup of the population-based HELIAD cohort, a fairly representative cohort of the older Greek population. Verbal and non-verbal memory were assessed using the Greek Verbal Learning Test and Medical College of Georgia-Complex Figure Test. Baseline and longitudinal associations of memory performance with age, sex and formal education were explored with linear regression analysis and generalized estimated equations. RESULTS: A total of 1607 predominantly female (60%) individuals (73.82 ± 5.43 years), with a mean educational attainment of 8.17(±4.86) years were CN at baseline. Baseline analysis revealed a continuum of memory decline with aging and lower educational attainment. Women performed better in composite and verbal memory measures, while men performed better in non-verbal memory tasks. A subgroup of 761 participants with available assessments after 3.07(±0.82) years remained CN at follow-up. Composite memory scores yearly diminished by an additional 0.007 of a SD for each additional year of age at baseline. Regarding verbal learning, immediate free verbal recall, delayed free verbal recall and delayed cued verbal recall, an additional yearly decrease of 0.107, 0.043, 0.036 and 0.026 words were respectively recorded at follow-up, for each additional year of age at baseline. Women underwent steeper yearly decreases of 0.227 words in delayed cued verbal recall. No significant longitudinal associations emerged for immediate non-verbal memory, delayed non-verbal memory and immediate cued verbal recall. CONCLUSIONS: In the present study, aging (but not educational attainment) was consistently associated with steeper verbal memory decline.Supplemental data for this article is available online at https://doi.org/10.1080/13854046.2022.2059011 .

Evaluation of the Efficacy and Feasibility of a Telerehabilitation Program Using Language and Cognitive Exercises in Multi-Domain Amnestic Mild Cognitive Impairment.

OBJECTIVE: The aim of the present study was to investigate the efficacy and feasibility of a telerehabilitation program in multi-domain amnestic Mild Cognitive Impairment (md-aMCI). The study sample consisted of 30 patients with md-aMCI and aged 60-80 years. METHODS: The participants were randomly divided into two groups. The Training Group (TG), which received cognitive training by using the RehaCom software as well as paper-pencil language training and the Control Group (CG) which received standard clinical care (e.g., psychotherapy or/and physiotherapy). Duration of the telerehabilitation intervention was 15 weeks (twice a week for 60 min/session). RESULTS: Our results revealed that the neuropsychological performance of the TG group after the telerehabilitation intervention improved on a statistically significant level on the domains of delayed and working memory, confrontation naming, verbal fluency, and global cognition. Comparison between the TG and CG revealed a significant impact of the telerehabilitation program on the domains of memory (delay and working) and language (naming and verbal fluency) as well as global cognition performance. CONCLUSION: The findings of the study are promising in that the telerehabilitation intervention appears to be a useful method in improving or stabilizing cognitive decline in md-aMCI individuals and was a particularly effective alternative approach during the period of the pandemic lockdown. Specifically, the beneficial impact of the telerehabilitation intervention on episodic memory (which is one of the first domains to show impairment in md-aMCI patients) provides us with hope and evidence that these types of interventions may be applied with similar success using face-to-face interventions.

Language performance as a prognostic factor for developing Alzheimer's clinical syndrome and mild cognitive impairment: Results from the population-based HELIAD cohort.

OBJECTIVES: There is limited research on the prognostic value of language tasks regarding mild cognitive impairment (MCI) and Alzheimer's clinical syndrome (ACS) development in the cognitively normal (CN) elderly, as well as MCI to ACS conversion. METHODS: Participants were drawn from the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. Language performance was evaluated via verbal fluency [semantic (SVF) and phonemic (PVF)], confrontation naming [Boston Naming Test short form (BNTsf)], verbal comprehension, and repetition tasks. An additional language index was estimated using both verbal fluency tasks: SVF-PVF discrepancy. Cox proportional hazards analyses adjusted for important sociodemographic parameters (age, sex, education, main occupation, and socioeconomic status) and global cognitive status [Mini Mental State Examination score (MMSE)] were performed. RESULTS: A total of 959 CN and 118 MCI older (>64 years) individuals had follow-up investigations after a mean of ∼3 years. Regarding the CN group, each standard deviation increase in the composite language score reduced the risk of ACS and MCI by 49% (8-72%) and 32% (8-50%), respectively; better SVF and BNTsf performance were also independently associated with reduced risk of ACS and MCI. On the other hand, using the smaller MCI participant set, no language measurement was related to the risk of MCI to ACS conversion. CONCLUSIONS: Impaired language performance is associated with elevated risk of ACS and MCI development. Better SVF and BNTsf performance are associated with reduced risk of ACS and MCI in CN individuals, independent of age, sex, education, main occupation, socioeconomic status, and MMSE scores at baseline.

Language Differences Among Individuals with Normal Cognition, Amnestic and Non-Amnestic MCI, and Alzheimer's Disease.

OBJECTIVE: To investigate differences in language performance among older adults with normal cognition (CN), mild cognitive impairment (MCI), and Alzheimer's disease (ad). Owing to the conflicting literature concerning MCI, discrepancies between amnestic (aMCI) and non-amnestic MCI (naMCI) were explored in greater detail. METHOD: The study sample was drawn from the older (>64 years) HELIAD cohort. Language performance was assessed via semantic and phonemic fluency, confrontation naming, verbal comprehension, verbal repetition as well as a composite language index. Age, sex, and education adjusted general linear models were used to quantify potential pairwise differences in language performance. RESULTS: The present analysis involved 1607 participants with CN, 146 with aMCI [46 single and 100 multi-domain aMCI], 92 with naMCI [41 single and 51 multi-domain naMCI], and 79 with ad. The mean age and education of our predominantly female (60%) participants were 73.82 (±5.43) and 7.98 (±4.93) years, respectively. MCI individuals performed between those with CN and ad, whereas participants with aMCI performed worse compared to those with naMCI, especially in the semantic fluency and verbal comprehension tasks. Discrepancies between the aMCI and naMCI groups were driven by the exquisitely poor performance of multi-domain aMCI subgroup. CONCLUSIONS: Overall, individuals could be hierarchically arranged in a continuum of language impairment with the CN individuals constituting the healthy reference and naMCI, aMCI, ad patients representing gradually declining classes in terms of language performance. Exploration of language performance via separation of single from multi-domain naMCI provided a potential explanation for the conflicting evidence of previous research.

Cognitive trajectories preluding the imminent onset of Alzheimer's disease dementia in individuals with normal cognition: results from the HELIAD cohort.

BACKGROUND: The cognitive trajectories of cognitively normal (CN) individuals rapidly progressing to Alzheimer's disease dementia (AD) have not been investigated. AIM: To explore the preclinical pattern of cognitive performance heralding the rapid progression from normal cognition to AD. METHODS: The HELIAD cohort underwent comprehensive neuropsychological assessments (memory, language, attention, executive and visuo-perceptual functions) at baseline and after approximately 3-year intervals. The cognitive trajectories of those with normal cognition at baseline were explored according to the follow-up diagnosis using adjusted generalised estimating equations analyses. RESULTS: A total of 932 predominantly female (61%), older (72.9 ± 4.9), CN participants were followed for 3.09 (± 0.83) years. Among them, 761 individuals remained CN, 29 progressed to AD and 142 developed MCI (33 single-domain amnestic, 41 multidomain amnestic, 37 single-domain non-amnestic and 31 multidomain non-amnestic). Those progressing to AD were already performing worse than the healthy reference in every single cognitive domain at baseline. Cognitive deficits ranged between ~ 0.5SD (attention, executive function and language) and ~ 1.0SD (memory and visuo-perceptual skills). Throughout the 3-year follow-up, memory constantly exhibited the most prominent impairment compared to the remaining cognitive domains while executive function diminished in the most abrupt fashion (~ 0.19SD yearly) separating from the remaining three cognitive functions before the development of full-blown AD. Heterogeneous patterns of cognitive decline clearly differentiated those progressing to MCI from those rapidly converting to AD, as well. DISCUSSION: Poor performance in every cognitive domain may characterise cognitively normal individuals at high risk of fast progression to AD. CONCLUSION: Strict neuropsychological cut-offs fail to detect a considerable number of individuals at high risk of rapid progression to AD.