Effect of emotional valence on true and false recognition controlling arousal.

The aim of our experiment was to analyse the effect of the emotional valence (positive, negative, or neutral) on true and false recognition, matching the arousal, frequency, concreteness, and associative strength of the study and recognition words. Fifty younger adults and 46 healthy older adults performed three study tasks (with words of different valence: positive, negative, neutral) and their corresponding recognition tests. Two weeks later, they performed the three recognition tests again. The results show that words with a negative valence produced less true recognition and less false recognition than words with a positive or neutral valence, in both younger and older adults, on the immediate recognition test. This pattern of results was also found in the younger adults on the delayed recognition test, whereas in the older participants, these differences disappeared. Thus, when arousal is controlled, both younger and older adults tend to recognise negative information worse than positive or neutral information, but they also commit fewer errors. Results would suggest that the greater arousal commonly associated with negative stimuli, rather than their own valence, could explain some of the contradictory results found in the literature.

Transcranial Direct Current Stimulation Intervention in Alzheimer's Disease and Its Follow-Up.

BACKGROUND: Alzheimer's disease (AD) stands as the prevailing type of dementia, marked by gradual memory loss and cognitive decline. Transcranial direct current stimulation (tDCS) is a non-invasive method used to regulate cortical brain function and has been explored as a potential treatment for cognitive impairment. OBJECTIVE: This study aimed to compare the effects of daily home-based active or sham tDCS on cognitive function in patients with early-stage AD and its follow-up after one month. METHODS: The study involved a randomized, blinded, and controlled-placebo design, with 18 participants enrolled. The primary outcome measures were general cognitive function, immediate, and delayed recall, and executive function. Participants included in the study were randomly assigned to the anodal and sham tDCS groups. Participants were assessed before and after the intervention and one month after the end of treatment. The home-based intervention was applied for 5 consecutive days, daily. RESULTS: The results showed a significant interaction between the active and sham groups; in particular, improvements in MMSE scores, immediate memory and delayed recall were observed at one-month follow-up in the active group. CONCLUSIONS: The positive effects of tDCS on cognitive function in AD patients observed suggest that tDCS may induce long-term neuroplastic changes, leading to sustained improvements in cognitive abilities.

Study of the diagnostic efficiency of anti-ZnT8 autoantibodies for type 1 diabetes in pediatric patients.

OBJECTIVE: Zinc transporter 8 autoantibodies (ZNt8A) are 1 of the 4 main autoantibodies used for the diagnosis of type 1 diabetes (T1D), with glutamic acid decarboxylase autoantibodies (GADA), islet antigen-2 autoantibodies (IA-2A), and insulin autoantibodies (IAA). The objective of this study is to evaluate the diagnostic efficiency of these autoantibodies for the diagnosis of T1D in pediatric patients. METHODS: A retrospective analysis of patients under 16 years of age with suspected T1D was made between June 2020 and January 2021. A total of 80 patients were included in the study, with 1 sample per patient. Subjects were classified according to diagnosis. RESULTS: Of the subjects included in the study, 50 developed T1D. The diagnostic efficacy was IA-2A (cutoff ≥ 28 U/L) sensitivity 0.26 (95% CI: 0.14-0.38) and specificity 0.97 (95% CI: 0.79-1.0); GADA (cutoff ≥ 17 U/mL) sensitivity 0.40 (95% CI: 0.26-0.54) and specificity 0.87 (95% CI: 0.75-0.99); ZnT8A (cut off ≥ 15 U/L) sensitivity 0.62 (95% CI: 0.49-0.75) and specificity 0.97 (95% CI: 0.90-1.0). ZnT8A obtained the most significantly global diagnostic accuracy (0.75), and GADA with ZnT8A showed the highest correlation. CONCLUSION: The results obtained indicate a higher efficiency of anti-ZnT8 autoantibodies for the diagnosis of T1D in pediatric patients. Clinical efficiency of diabetic autoantibodies is method and assay dependent and influences combined diagnostic strategies.

Genistein effect on cognition in prodromal Alzheimer's disease patients. The GENIAL clinical trial.

BACKGROUND: Delaying the transition from minimal cognitive impairment to Alzheimer's dementia is a major concern in Alzheimer's disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer's dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model. METHODS: In this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer's disease patients. The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T), Clock Drawing Test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test. RESULTS: We report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p = 0.031; dichotomized delayed Centil REY copy p = 0.002 and a tendency to improve in all the rest of them. The amyloid-beta deposition analysis showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878), while placebo-treated did increase it (p = 0.036). We did not observe significant changes in other brain areas studied. CONCLUSIONS: This study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer's dementia in patients with prodromal Alzheimer's disease. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study. TRIAL REGISTRATION: NCT01982578, registered on November 13, 2013.

Enhancing Immediate Memory, Potential Learning, and Working Memory with Transcranial Direct Current Stimulation in Healthy Older Adults.

BACKGROUND: Transcranial direct current stimulation (tDCS) has emerged as a prevention method or minimizer of the normal cognitive deterioration that occurs during the aging process. tDCS can be used to enhance cognitive functions such as immediate memory, learning, or working memory in healthy subjects. The objective of this study was to analyze the effect of two 20-min sessions of anodal transcranial direct stimulation on immediate memory, learning potential, and working memory in healthy older adults. METHODS: A randomized, single-blind, repeated-measures, sham-controlled design was used. The sample is made up of 31 healthy older adults, of whom 16 were in the stimulation group and 15 were in the sham group. The anode was placed on position F7, coinciding with the left dorsolateral prefrontal cortex region, and the cathode was placed on Fp2, the right supraorbital area (rSO). RESULTS: When comparing the results of the treatment group and the sham group, differences were observed in working memory and learning potential; however, no differences in immediate memory were found. CONCLUSION: The results showed that tDCS is a non-invasive and safe tool to enhance cognitive processes in healthy older adults interested in maintaining some cognitive function.

Effectiveness of tDCS at Improving Recognition and Reducing False Memories in Older Adults.

BACKGROUND: False memories tend to increase in healthy and pathological aging, and their reduction could be useful in improving cognitive functioning. The objective of this study was to use an active-placebo method to verify whether the application of transcranial direct current stimulation (tDCS) improved true recognition and reduced false memories in healthy older people. METHOD: Participants were 29 healthy older adults (65-78 years old) that were assigned to either an active or a placebo group; the active group received anodal stimulation at 2 mA for 20 min over F7. An experimental task was used to estimate true and false recognition. The procedure took place in two sessions on two consecutive days. RESULTS: True recognition showed a significant main effect of sessions (p < 0.01), indicating an increase from before treatment to after it. False recognition showed a significant main effect of sessions (p < 0.01), indicating a decrease from before treatment to after it and a significant session × group interaction (p < 0.0001). CONCLUSIONS: Overall, our results show that tDCS was an effective tool for increasing true recognition and reducing false recognition in healthy older people, and suggest that stimulation improved recall by increasing the number of items a participant could recall and reducing the number of memory errors.

Phonological false recognition, recollection, and familiarity in healthy aging and alzheimer's disease / Falso reconocimiento fonológico, recolección y familiaridad en el envejecimiento y la enfermedad de Alzheimer

BACKGROUND: Thirty healthy older people, 20 Alzheimer's disease patients (matched on age and education level) and 33 young people, participated in an experiment to implicitly induce phonological false memories, allowing us to obtain estimates of their recollection, familiarity, and false recognition. METHOD: In the study task, words were selected which used half of the letters in the alphabet. In the recognition test, there were three types of non-studied new words: critical lures using letters from the same half of the alphabet as the study task words; distractors formed using the unused half of the alphabet, and distractors formed using all the letters in the alphabet. RESULTS: Results showed that: (a) in all the samples, critical lures produced more false recognitions than distractors composed of all the letters in the alphabet or distractors composed of the letters not used in the study, showing a significant phonological false recognition effect; (b) both recollection and familiarity declined with age and dementia; (c) phonological false recognition increased with age and Alzheimer's disease. CONCLUSIONS: These results seem to support the idea that estimates of recollection, familiarity, and phonological false recognition can be used as early markers of cognitive impairment

ANTECEDENTES: treinta personas mayores sanas, 20 pacientes con enfermedad de Alzheimer (igualados en edad y nivel educativo) y 33 jóvenes participaron en un experimento para inducirles implícitamente falsas memorias fonológicas, permiténdonos obtener sus estimaciones de recolección, familiaridad y falso reconocimiento. MÉTODO: en la tarea de estudio las palabras estaban formadas por una mitad de las letras del alfabeto. En el test de reconocimiento había tres tipos de palabras nuevas no estudiadas: palabras críticas formadas por las mismas letras de la tarea de estudio, distractores formados por la otra mitad de letras no utilizadas en la tarea de estudio y distractores formados por todas las letras del alfabeto. RESULTADOS: los resultados mostraron que: (a) en las tres muestras las palabras críticas producían más falsos reconocimientos que en ambos tipos de distractores, mostrando un claro efecto significativo de falso reconocimiento fonológico; (b) tanto la recolección como la familiaridad disminuían durante el envejecimiento y la enfermedad de Alzheimer; (c) el falso reconocimiento fonológico aumentaba durante el envejecimiento y la enfermedad de Alzheimer. CONCLUSIONES: nuestros resultados apoyan la idea de que las estimaciones de recolección, familiaridad y falso reconocimiento fonológico pueden ser utililizadas como marcadores tempranos de deterioro cognitivo

Phonological false recognition, recollection, and familiarity in healthy aging and Alzheimer's disease.

BACKGROUND: Thirty healthy older people, 20 Alzheimer's disease patients (matched on age and education level) and 33 young people, participated in an experiment to implicitly induce phonological false memories, allowing us to obtain estimates of their recollection, familiarity, and false recognition. METHOD: In the study task, words were selected which used half of the letters in the alphabet. In the recognition test, there were three types of non-studied new words: critical lures using letters from the same half of the alphabet as the study task words; distractors formed using the unused half of the alphabet, and distractors formed using all the letters in the alphabet. RESULTS: Results showed that: (a) in all the samples, critical lures produced more false recognitions than distractors composed of all the letters in the alphabet or distractors composed of the letters not used in the study, showing a significant phonological false recognition effect; (b) both recollection and familiarity declined with age and dementia; (c) phonological false recognition increased with age and Alzheimer's disease. CONCLUSIONS: These results seem to support the idea that estimates of recollection, familiarity, and phonological false recognition can be used as early markers of cognitive impairment.

Conflict monitoring on an emotional Stroop task. Comparison of healthy older adults and patients with major neurocognitive disorders due to probable AD.

INTRODUCTION: The conflict monitoring system exerts an influence on centers responsible for cognitive control, causing them to intervene more strongly in processing when conflict occurs. These mechanisms are usually investigated through specific tasks where there is an inherent interference elicited by the congruency or incongruency between the stimuli and responses, such as the Stroop task. In studies of emotional conflict, one hypothesis related to the dorsal anterior cingulate cortex (ACC) is that it serves, in part, to signal the appearance of conflicts, thus triggering compensatory adjustments. This study aims to verify whether the conflict monitoring hypothesis is confirmed in a group with Alzheimer's disease and, therefore, whether they exhibit a reduction in their reaction times. METHOD: A group of healthy older adults (HOA) and a group with Major Neurocognitive Disorders due to probable AD were evaluated to test the conflict monitoring hypothesis with an emotional Stroop task. RESULTS: A significant interaction was obtained on the word and faces blocks. In the HOA group, a reduction in reaction times was observed, whereas in the AD groups, no reduction in reaction times was obtained. CONCLUSIONS: Whereas in HOA the conflict monitoring hypothesis is confirmed, in the Major Neurocognitive Disorders due to probable AD group there is no reduction in their reaction times on the high conflict resolution trials (incongruent trials that follow incongruent trials) due to their difficulty in making compensatory adjustments to cognitive control that help them to reduce conflict and improve their success rate.

A cross-sectional and longitudinal study on the protective effect of bilingualism against dementia using brain atrophy and cognitive measures.

BACKGROUND: Evidence from previous studies suggests that bilingualism contributes to cognitive reserve because bilinguals manifest the first symptoms of Alzheimer's disease (AD) up to 5 years later than monolinguals. Other cross-sectional studies demonstrate that bilinguals show greater amounts of brain atrophy and hypometabolism than monolinguals, despite sharing the same diagnosis and suffering from the same symptoms. However, these studies may be biased by possible pre-existing between-group differences. METHODS: In this study, we used global parenchymal measures of atrophy and cognitive tests to investigate the protective effect of bilingualism against dementia cross-sectionally and prospectively, using a sample of bilinguals and monolinguals in the same clinical stage and matched on sociodemographic variables. RESULTS: Our results suggest that the two groups did not differ in their cognitive status at baseline, but bilinguals had less parenchymal volume than monolinguals, especially in areas related to brain atrophy in dementia. In addition, a longitudinal prospective analysis revealed that monolinguals lost more parenchyma and had more cognitive decline than bilinguals in a mean follow-up period of 7 months. CONCLUSION: These results provide the first prospective evidence that bilingualism may act as a neuroprotective factor against dementia and could be considered a factor in cognitive reserve.

Distance disintegration delineates the brain connectivity failure of Alzheimer's disease.

Alzheimer's disease (AD) is associated with brain network dysfunction. Network-based investigations of brain connectivity have mainly focused on alterations in the strength of connectivity; however, the network breakdown in AD spectrum is a complex scenario in which multiple pathways of connectivity are affected. To integrate connectivity changes that occur under AD-related conditions, here we developed a novel metric that computes the connectivity distance between cortical regions at the voxel level (or nodes). We studied 114 individuals with mild cognitive impairment, 24 with AD, and 27 healthy controls. Results showed that areas of the default mode network, salience network, and frontoparietal network display a remarkable network separation, or greater connectivity distances, from the rest of the brain. Furthermore, this greater connectivity distance was associated with lower global cognition. Overall, the investigation of AD-related changes in paths and distances of connectivity provides a novel framework for characterizing subjects with cognitive impairment; a framework that integrates the overall network topology changes of the brain and avoids biases toward unreferenced connectivity effects.

Activity in Memory Brain Networks During Encoding Differentiates Mild Cognitive Impairment Converters from Non-Converters.

Alzheimer's disease (AD) has been associated with memory impairment due to alterations in the medial temporal lobe (MTL) and the precuneus. Therefore, the goal of this study was to investigate the effects of AD on the brain networks associated with the hippocampus and precuneus during an encoding memory task. 68 mild cognitive impairment patients (MCI), 21 AD patients, and 20 healthy controls (HC) were included. Participants were instructed to memorize landscapes while undergoing fMRI scanning, followed by a recognition test. MCI were followed up clinically for 18 months to track conversion status. Independent component analysis (ICA) was performed to investigate AD effects on precuneus and MTL networks during memory encoding. Behavioral analyses indicate that HC had a better performance than MCI converters (MCIc) and AD. ICA showed that MCIc had significantly higher activation in the MTL-associated network than MCI non converters (MCIn) and AD, including bilateral hippocampus, parahippocampus, and fusiform gyrus. Furthermore, the precuneus-associated network fitted the default mode network, showing a negative correlation with behavioral performance. These findings indicate that the hyperactivation of the hippocampal network displayed by MCIc has potential discrimination capacity to distinguish them of MCIn, and could be interpreted as a compensatory mechanism.

Type of memory and emotional valence in healthy aging, mild cognitive impairment, and alzheimer's disease / Tipo de memoria y valencia emocional en adultos mayores sanos, deterioro cognitivo leve y enfermedad de Alzheimer

Background: Autobiographical memory (AM) presents components related to the type of memory and may present an associated emotional valence. Comparing healthy older adults, adults with mild cognitive impairment (MCI), and adults with Alzheimer's disease (AD) gives contradictory results. We examined AM in these groups to analyze differences and provide information that would contribute to the understanding of AM and associated emotional deficits in patients. Method: 31 AD, 32 MCI, and 32 healthy older adults were evaluated using the Autobiographical Memory Test. Taking the number of memories elicited in each category as a dependent variable, an ANOVA of three groups × 3 types of valence was applied (positive, negative, neutral, intrasubject), and another ANOVA of 3 groups × 3 types of memory (specific, general, vague, intrasubject). Results: specific-type responses are reduced with the progression of the pathology and in addition healthy subjects have a positive valence while AD presents a mainly neutral valence. Conclusions: Cognitive problems associated with aging tend to affect the highest level of AM specificity. Healthy subjects and MCI have memories with an emotional valence, whereas the AD group has a significant deterioration in these memories

Antecedentes: la memoria autobiográfica (MA) presenta componentes relacionados con el tipo de recuerdo y una valencia emocional asociada a este. Los resultados al comparar adultos mayores sanos, deterioro cognitivo leve (DCL) y enfermedad de Alzheimer (EA) son contradictorios. Se evaluó la MA de estos grupos para analizar diferencias y ofrecer información que contribuya a la comprensión de la MA y los déficits emocionales asociados a los pacientes. Método: 31 AD, 32 MCI y 32 adultos mayores sanos fueron evaluados con el Test de Memoria Autobiográfica. Tomando como variable dependiente el número de memorias elicitadas en cada categoría se aplicó un ANOVA de tres grupos × 3 tipos de valencia (positiva, negativa, neutra; intrasujeto), y otro ANOVA de 3 grupos × 3 tipos de recuerdo (específico, general, vago; intrasujeto). Resultados: las respuestas específicas se reducen con la progresión de la patología y los sanos presentan mayor recuerdo positivo y los EA principalmente valencias neutras. Conclusiones: los problemas cognitivos asociados con el envejecimiento tienden a afectar el nivel más alto de especificidad de la MA. Los sujetos sanos y DCL presentan recuerdos con valencia emocional, mientras que los EA tiene un deterioro significativo en los recuerdos y su asociación a las emociones

Executive Functions, Episodic Autobiographical Memory, Problem-Solving Capacity, and Depression Proposal for a Structural Equations Model.

The executive functions play an important role in storing and recovering autobiographical memories, especially episodic memories. These types of memories provide information about solutions and experiences from the past that can be utilized as examples in the present when seeking solutions to any problem. In addition, a close relationship between depression and the executive functions has been widely recognized. This study aims to elaborate a structural equations model that empirically supports the relationships among the executive functions, episodic autobiographical memory, and the adaptive capacity to solve problems, taking into account the depressed mood state. In all, 32 healthy elderly people, 32 patients with Parkinson disease, 32 with amnestic mild cognitive impairment, and 32 with Alzheimer disease were evaluated. Structural equation models were estimated to test the effects among the constructs. The final model shows adequate fit indexes, thus revealing that an individual's problem-solving capacity will depend on the capacity to access the episodic autobiographical memory, which in turn will depend on the maintenance of executive functioning. In a parallel way, the mood state, and specifically depression, will play a modulator role because when there is depressive symptomatology, some capacities that depend on executive control can be diminished.

Type of memory and emotional valence in healthy aging, mild cognitive impairment, and Alzheimer's disease.

BACKGROUND: Autobiographical memory (AM) presents components related to the type of memory and may present an associated emotional valence. Comparing healthy older adults, adults with mild cognitive impairment (MCI), and adults with Alzheimer's disease (AD) gives contradictory results. We examined AM in these groups to analyze differences and provide information that would contribute to the understanding of AM and associated emotional deficits in patients. METHOD: 31 AD, 32 MCI, and 32 healthy older adults were evaluated using the Autobiographical Memory Test. Taking the number of memories elicited in each category as a dependent variable, an ANOVA of three groups x 3 types of valence was applied (positive, negative, neutral, intrasubject), and another ANOVA of 3 groups x 3 types of memory (specific, general, vague, intrasubject). RESULTS: Specific-type responses are reduced with the progression of the pathology and in addition healthy subjects have a positive valence while AD presents a mainly neutral valence. CONCLUSIONS: Cognitive problems associated with aging tend to affect the highest level of AM specificity. Healthy subjects and MCI have memories with an emotional valence, whereas the AD group has a significant deterioration in these memories.

Phonological false recognition produced by bottom-up automatic activation in young and older people.

Two experiments explored a new procedure to implicitly induce phonological false memories in young and older people. On the study tasks, half of the words were formed from half of the letters in the alphabet, whereas the remaining words were formed from all the letters in the alphabet. On the recognition tests, there were three types of non-studied new words: critical lures formed from the same half of the letters as the studied words; distractors formed from the other half of the letters not used, and distractors formed from all the letters in the alphabet. In both experiments, the results showed that, in both young and older people, critical lures produced more false recognitions than distractors composed of all the letters in the alphabet, which, in turn, produced more false alarms than distractors composed of the letters not used during the study. These results support the predictions of the activation/monitoring models, which assume that false memories are partly due to activation spreading from items (semantically or phonologically) related to the critical words.

Wellbeing, resilience, and coping: Are there differences between healthy older adults, adults with mild cognitive impairment, and adults with Alzheimer-type dementia?

The changes that occur with cognitive impairment and Alzheimer's disease could affect psychological aspects unrelated to memory. The purpose of this study is to compare 32 healthy older adults, 31 amnestic mild cognitively impaired (aMCI) adults, and 32 patients diagnosed with Alzheimer's disease (AD), in order to determine whether there are differences in their psychological wellbeing, resilience, and coping strategies. Unifactorial MANOVAS and ANOVAS were performed to analyze the between-group differences. The results reveal that the AD group showed lower levels of resilience and orientation toward problem-solving and greater use of religious strategies. In addition, they had significantly lower wellbeing scores than the other groups. The worsening of the pathology impedes the capacity for adaptation and resilience and the application of strategies oriented toward the problem, and it increases the application of strategies based on magical thinking. Moreover, it also produces a reduction in wellbeing.

Motivated forgetting reduces veridical memories but slightly increases false memories in both young and healthy older people.

The aim of the current study is to examine the effects of motivated forgetting and aging on true and false memory. Sixty young and 54 healthy older adults were instructed to study two lists of 18 words each. Each list was composed of three sets of six words associated with three non-presented critical words. After studying list 1, half of the participants received the instruction to forget List 1, whereas the other half received the instruction to remember List 1. Next, all the subjects studied list 2; finally, they were asked to remember the words studied in both lists. The results showed that when participants intended to forget the studied List 1, they were less likely to recall the studied words, but more likely to intrude the critical words. That is, we can intentionally forget something but this can also entail the intrusion of some related false memories.

Effects of Stimuli Repetition and Age in False Recognition.

The aim of the current study is to examine the effects of stimuli repetition and age in false recognition using the Deese-Roediger-McDermott experimental paradigm. Two matched samples of 32 young adults and 32 healthy older adults studied 10 lists of six words associated with three non-presented critical words. On half of the lists, the words were presented once, and on the other five lists, the words were presented three times, always following a same sequential order. After each study list, participants performed a self-paced recognition test containing 12 words: the 6 studied words and 6 other non-studied words (the 3 critical words and 3 distractors). The results show that false recognition increases with age and declines in both samples with repetitions (although more in the young adults than in the older people). Results are discussed in relation to the dual-process theories of (false) memory.

Complexity analysis of cortical surface detects changes in future Alzheimer's disease converters.

Alzheimer's disease (AD) is a neurological disorder that creates neurodegenerative changes at several structural and functional levels in human brain tissue. The fractal dimension (FD) is a quantitative parameter that characterizes the morphometric variability of the human brain. In this study, we investigate spherical harmonic-based FD (SHFD), thickness, and local gyrification index (LGI) to assess whether they identify cortical surface abnormalities toward the conversion to AD. We study 33 AD patients, 122 mild cognitive impairment (MCI) patients (50 MCI converters and 29 MCI nonconverters), and 32 healthy controls (HC). SHFD, thickness, and LGI methodology allowed us to perform not only global level but also local level assessments in each cortical surface vertex. First, we found that global SHFD decreased in AD and future MCI converters compared to HC, and in MCI converters compared to MCI nonconverters. Second, we found that local white matter SHFD was reduced in AD compared to HC and MCI mainly in medial temporal lobe. Third, local white-matter SHFD was significantly reduced in MCI converters compared to MCI nonconverters in distributed areas, including the medial frontal lobe. Thickness and LGI metrics presented a reduction in AD compared to HC. Thickness was significantly reduced in MCI converters compared to healthy controls in entorhinal cortex and lateral temporal. In summary, SHFD was the only surface measure showing differences between MCI individuals that will convert or remain stable in the next 4 years. We suggest that SHFD may be an optimal complement to thickness loss analysis in monitoring longitudinal changes in preclinical and clinical stages of AD. Hum Brain Mapp 38:5905-5918, 2017. © 2017 Wiley Periodicals, Inc.