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

• Keywords
• Alzheimer’s disease, challenging tests, free and cued verbal memory, medial temporal lobe atrophy, mild cognitive impairment, semantic memory binding, subjective cognitive decline,
• MeSH
• Dementia * diagnosis   MeSH
• Hippocampus MeSH
• Cognition MeSH
• Memory, Short-Term MeSH
• Humans MeSH
• Mental Recall * MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Memory impairment has been considered as one of the earliest clinical hallmarks of Alzheimer's disease. This paper summarizes recent progress in the assessment of memory impairment in predementia stages. New promising approaches of memory assessment include evaluation of longitudinal cognitive changes, assessment of long-term memory loss, evaluation of subjective cognitive concerns and testing of other memory modalities, such as spatial memory. In addition, we describe new challenging memory tests based on memory binding paradigms that have been recently developed and are currently being validated.

• Keywords
• Alzheimer's disease, Elderly, memory binding, memory impairment, mild cognitive impairment, neuropsychological assessment, spatial memory, subjective cognitive decline.,
• MeSH
• Alzheimer Disease complications   diagnosis   MeSH
• Early Diagnosis * MeSH
• Humans MeSH
• Memory Disorders diagnosis   etiology   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

OBJECTIVE: The present study aims to examine whether declarative memory dysfunction relates to impaired core memory mechanisms or attentional and executive dysfunction in idiopathic REM Sleep Behavior Disorder (iRBD). METHOD: In this observational, cross-sectional study, were enrolled 82 individuals with the diagnosis of iRBD according to the International Classification of Sleep Disorders and 49-matched healthy controls fulfilling inclusion criteria. All participants underwent two memory tasks, namely the Rey Auditory Verbal Learning Test (RAVLT) and Memory Binding Test (MBT), which include conditions of varying degrees of dependence on executive functioning, as well as different indicators of core memory processes (e.g., learning, retention, relational binding). RESULTS: We used Bayesian multivariate generalized linear model analysis to evaluate the effect of iRBD on memory performance controlled for effects of age and sex. Individuals with iRBD displayed worse memory performance in the delayed free recall task (b = -0.37, 95% PPI [-0.69, -0.05]), but not on delayed recognition of the same material. Their performance in cued recall tasks both in immediate and delayed conditions was in comparison to controls relatively spared. Moreover, the deficit in delayed free recall was mediated by attention/processing speed. CONCLUSIONS: In iRBD, we replicated findings of reduced free recall based on inefficient retrieval (retrieval deficit), which was small in terms of effect size. Importantly, the memory profile across measures does not support the presence of core memory dysfunction, such as poor learning, retention or associative binding.

• Keywords
• RBD (rapid eye movement (REM) sleep behavior disorder), cued recall, free recall, iRBD (idiopathic rapid eye movement (REM) sleep behavior disorder), memory binding, memory impairment,
• MeSH
• Bayes Theorem MeSH
• Cognitive Dysfunction * diagnosis   MeSH
• Humans MeSH
• Neuropsychological Tests MeSH
• REM Sleep Behavior Disorder * complications   MeSH
• Memory Disorders diagnosis   MeSH
• Cross-Sectional Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

Prenatal exposure to caffeine can cause developmental problems. This study determined chronic influence of prenatal caffeine at relatively higher doses on cognitive functions in the rat offspring. Pregnant Sprague-Dawley rats (4-month-old) were exposed to caffeine (20 mg/kg, twice a day) for whole pregnancy from gestational day 4. Fetal and offspring body and brain weight was measured. Learning and memory were tested in adult offspring with Morris water maze. Learning and memory-related receptors were measured. The exposure to prenatal caffeine not only caused fetal growth restriction, but also showed long-term effects on learning and memory in the offspring. The caffeine offspring exhibited longer escape latency and path length in navigation testing. The number of passing the target was significantly reduced in those offspring. The expression of adenosine A(1) and A(2A) receptors, nuclear PKA C(alpha), C(beta) subunits, and pCREB were significantly increased in the fetal and neonatal brain, and suppressed in the hippocampus of the adult offspring. The expression of BDNF and TrkB were reduced regardless of various ages. The results suggest that intrauterine programming dysfunction of adenosine receptors and the down-stream of cAMP/PKA/pCREB system may play an important role in prenatal caffeine induced cognition disorders in the adult offspring.

• MeSH
• Maze Learning drug effects   physiology   MeSH
• Caffeine toxicity   MeSH
• Rats MeSH
• Brain-Derived Neurotrophic Factor metabolism   MeSH
• Memory drug effects   physiology   MeSH
• Memory Disorders chemically induced   diagnosis   metabolism   MeSH
• Rats, Sprague-Dawley MeSH
• Cyclic AMP Response Element-Binding Protein metabolism   MeSH
• Cyclic AMP-Dependent Protein Kinases metabolism   MeSH
• Receptors, Purinergic P1 metabolism   MeSH
• Signal Transduction drug effects   physiology   MeSH
• Pregnancy MeSH
• Prenatal Exposure Delayed Effects chemically induced   diagnosis   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bdnf protein, rat MeSH Browser
• Creb1 protein, rat MeSH Browser
• Caffeine MeSH
• Brain-Derived Neurotrophic Factor MeSH
• Cyclic AMP Response Element-Binding Protein MeSH
• Cyclic AMP-Dependent Protein Kinases MeSH
• Receptors, Purinergic P1 MeSH

In an attempt to compare effects of different neurotrophic factors on impaired memory function, young adult naive rats were trained to find the hidden platform in the Morris water maze (3 consecutive days, eight trials/day). The fimbria-fornix was unilaterally removed by aspiration and nerve growth factor (NGF) (11 micrograms/ml and 0.5 microgram/ml; groups NGF and ngf, respectively) or basic fibroblast growth factor (bFGF) (0.2 microgram/ml, group FGF) were applied via intra-cerebroventricular infusion by the osmotic minipump (flow rate 0.5 microliter/h, 14 days). Nootropic drug Cerebrolysin (EBEWE Arzneitmittel; 2.5 ml/kg/day, group CER) was applied via intraperitoneal injection (14 days). One group was formed by the rats treated with NGF (11 micrograms/ml) and Cerebrolysin (group NGFCER). Non-lesioned and lesioned only rats served as controls (groups INT and LES). After a 14-day treatment, rats were tested using the retention test (1 day, four trials). On the next day, the rats were tested using transfer test (3 days, eight trials/day). Escape latency and length of trajectory was recorded. Groups NGF, ngf, FGF and LES were similarly impaired in their ability to retrieve the old position of the platform (retention test), as well as in their ability to navigate to the new position of the platform (transfer test). In the latter, NGF group significantly differed from lesioned animals. Groups CER and NGFCER were comparable to group INT in the retention or transfer test. It is concluded that anterograde amnesia elicited by fimbria-fornix lesion can be abbreviated by NGF and/or CER, while retrograde amnesia is absent only in rats treated by CER. No short-term influence of bFGF was found. It is suggested that biochemical systems other than the cholinergic one are involved.

• MeSH
• Amino Acids pharmacology   MeSH
• Maze Learning drug effects   MeSH
• Fibroblast Growth Factor 2 pharmacology   MeSH
• Hippocampus cytology   physiology   MeSH
• Rats MeSH
• Nerve Growth Factors pharmacology   MeSH
• Nootropic Agents pharmacology   MeSH
• Parasympathetic Nervous System cytology   drug effects   MeSH
• Memory Disorders drug therapy   psychology   MeSH
• Cell Survival drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amino Acids MeSH
• cerebrolysin MeSH Browser
• Fibroblast Growth Factor 2 MeSH
• Nerve Growth Factors MeSH
• Nootropic Agents MeSH

Frontotemporal lobar degeneration with transactive response DNA-binding protein 43 (FTLD-TDP) and progressive supranuclear palsy (PSP) are distinct neurodegenerations with different clinical presentations. We report two cases with FTLD-TDP and PSP in comorbidity: a patient with amnestic dementia developing frontal lobe dementia, Parkinsonism and supranuclear gaze palsy and a patient with cerebellar ataxia and nystagmus developing akinesia, rigidity, and subcortical dementia. Neuropathological examination revealed neuronal and glial tau pathology together with ubiquitin, and phospho-TDP-43-immunoreactivities in the hippocampus, striatum, mesencephalon, and frontal and temporal cortices. Clinical and neuropathological correlations in atypical neurodegenerations are crucial to describe new entities of overlapping syndromes.

• Keywords
• Progressive supranuclear palsy, TDP-43 inclusions, dementia, frontotemporal lobar degeneration, tauopathy,
• MeSH
• DNA-Binding Proteins metabolism   MeSH
• Frontotemporal Dementia complications   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain diagnostic imaging   metabolism   MeSH
• Neuropsychological Tests MeSH
• Supranuclear Palsy, Progressive complications   diagnostic imaging   pathology   MeSH
• Ubiquitin metabolism   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• DNA-Binding Proteins MeSH
• TARDBP protein, human MeSH Browser
• Ubiquitin MeSH

TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically diagnosed with Alzheimer's disease and a positive family history of ALS. We did not observe enrichment of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFκB induction. Of 3 common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13-1.9]; p-value 0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS cohorts.

• Keywords
• Early onset Alzheimer's disease, Frontotemporal dementia, Loss-of-function, RNA sequencing, TBK1,
• MeSH
• Alleles MeSH
• Alzheimer Disease genetics   MeSH
• Amyotrophic Lateral Sclerosis genetics   MeSH
• Frontotemporal Dementia genetics   MeSH
• Genetic Variation genetics   MeSH
• Genetic Association Studies * MeSH
• Heterozygote MeSH
• Homozygote MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Loss of Function Mutation genetics   MeSH
• Protein Serine-Threonine Kinases genetics   MeSH
• Risk MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• Protein Serine-Threonine Kinases MeSH
• TBK1 protein, human MeSH Browser