Localizing apraxia in corticobasal syndrome: a morphometric MRI study.

Apraxia localization has relied on voxel-based, lesion-symptom mapping studies in left hemisphere stroke patients. Studies on the neural substrates of different manifestations of apraxia in neurodegenerative disorders are scarce. The primary aim of this study was to look into the neural substrates of different manifestations of apraxia in a cohort of corticobasal syndrome patients (CBS) by use of cortical thickness. Twenty-six CBS patients were included in this cross-sectional study. The Goldenberg apraxia test (GAT) was applied. 3D-T1-weighted images were analyzed via the automated recon-all Freesurfer version 6.0 pipeline. Vertex-based multivariate General Linear Model analysis was applied to correlate GAT scores with cortical thickness. Deficits in imitation of meaningless gestures correlated with bilateral superior parietal atrophy, extending to the angular and supramarginal gyri, particularly on the left. Finger imitation relied predominantly on superior parietal lobes, whereas the left angular and supramarginal gyri, in addition to superior parietal lobes, were critical for hand imitation. The widespread bilateral clusters of atrophy in CBS related to apraxia indicate different pathophysiological mechanisms mediating praxis in neurodegenerative disorders compared to vascular lesions, with implications both for our understanding of praxis and for the rehabilitation approaches of patients with apraxia.

Genetic risk for Alzheimer's disease and adherence to the Mediterranean diet: results from the HELIAD study.

Obejctives: The aim of the current study was to investigate whether genetic risk factors may moderate the association between adherence to the Mediterranean diet and AD incidence.Mehtods: The sample was drawn from the HELIAD study, a longitudinal study with a follow-up interval of 3 years. In total 537 older adults without dementia or AD at baseline were included. Adherence to the Mediterranean diet was assessed at baseline and AD diagnosis was determined at both visits. A Polygenic Index for late onset AD (PGI-AD) was constructed. Cox proportional hazard models adjusted for age, sex, education, baseline Global cognition score and APOE e-4 genotype were employed to evaluate the association between PGI-AD and Mediterranean diet with AD incidence. Next, we examined the association between adherence to the Mediterranean diet and AD risk over time across participants stratified by low and high PGI-AD.Results: Twenty-eight participants developed AD at follow-up. In fully adjusted models both the PGI-AD and the adherence to the Mediterranean diet were associated with AD risk (p < 0.05 for both). In the low PGI-AD group, those with a low adherence had a 10-fold higher risk of developing AD per year of follow-up, than did the participants with a high adherence to the Mediterranean diet (p = 0.011), whereas no such association was found for participants in the high PGI-AD group.Discussion: The association of Mediterranean diet with AD risk is more prominent in the group of older adults with a low polygenic risk for developing AD. Our findings suggest that genetic risk factors should be taken into account when planning interventions aiming to improve cognitive health.

Dopamine transporter SPECT imaging in Parkinson's disease and atypical Parkinsonism: a study of 137 patients.

INTRODUCTION: Differential diagnosis between Parkinson's disease (PD) and multiple system atrophy-parkinsonian type (MSA-P), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), collectively termed atypical Parkinsonism (AP), is challenging. Dopamine transporter density imaging with Ioflupane I123 (DaTscan) is a marker of presynaptic nigrostriatal dysfunction. The primary aim of this study was to investigate the utility of DaTscan in the differential diagnosis of MSA-P, CBD, and PSP. METHODS: Patients examined at Eginition Hospital (2011-2021), with available DaTscan data and a diagnosis of probable AP, clinically established PD, as well as a neurological control (NC) group were included. Mean binding specific index (BSI), BSI of the most affected side, asymmetry index, laterality, and caudate/putamen ratio were recorded. Analyses were performed by Kruskal-Wallis and ANCOVA. RESULTS: 137 patients were included (CBD: [Formula: see text]; MSA-P: [Formula: see text]; PSP: [Formula: see text]; PD: [Formula: see text]; NC: [Formula: see text]). There were significant differences when comparing CBS, PSP, and NC vs. all other groups combined. Pairwise between-group comparisons revealed significant differences between PSP and CBD (mean striatum BSI>1.95; sensitivity 74.1%; specificity 85.0%), CBD and MSA-P (mean striatum BSI>2.04; sensitivity 70.4%; specificity 86.7%), and CBD and PD (mean striatum BSI>2.11; sensitivity 66.7%; specificity 100.0%). There were no differences between PSP, MSA-P, and PD. PSP, MSA-P, and PD differed from NC subjects, with 100% specificity and high sensitivity. Differentiation of NC from CBD was suboptimal. DISCUSSION: CBD patients exhibit relatively mild DaTscan abnormalities. DaTscan may assist in the differentiation of CBD from PSP. DaTscan does not differentiate among PD, MSA-P, and PSP.

CADASIL in Greece: Mutational spectrum and clinical characteristics based on a systematic review and pooled analysis of published cases.

BACKGROUND: Differences have been noted in the clinical presentation and mutational spectrum of CADASIL among various geographical areas. The aim of the present study was to investigate the mode of clinical presentation and genetic mutations reported in Greece. METHODS: After a systematic literature search, we performed a pooled analysis of all published CADASIL cases from Greece. RESULTS: We identified 14 studies that reported data from 14 families comprising 54 patients. Migraine with aura was reported in 39%, ischemic cerebrovascular diseases in 68%, behavioral-psychiatric symptoms in 47% and cognitive decline in 60% of the patients. The mean (±SD) age of onset for migraine with aura, ischemic cerebrovascular diseases, behavioral-psychiatric symptoms and cognitive decline was 26.2 ± 8.7, 49.3 ± 14.6, 47.9 ± 9.4 and 42.9 ± 10.3, respectively; the mean age at disease onset and death was 34.6 ± 12.1 and 60.2 ± 11.2 years. With respect to reported mutations, mutations in exon 4 were the most frequently reported (61.5% of all families), with the R169C mutation being the most common (30.8% of all families and 50% of exon 4 mutations), followed by R182C mutation (15.4% of all families and 25% of exon 4 mutations). CONCLUSIONS: The clinical presentation of CADASIL in Greece is in accordance with the phenotype encountered in Caucasian populations, but differs from the Asian phenotype, which is characterized by a lower prevalence of migraine and psychiatric symptoms. The genotype of Greek CADASIL pedigrees is similar to that of British pedigrees, exhibiting a high prevalence of exon 4 mutations, but differs from Italian and Asian populations, where mutations in exon 11 are frequently encountered.

Dopamine transporter SPECT imaging in corticobasal syndrome: A peak into the underlying pathology?

BACKGROUND: Multiple pathologies may underlie corticobasal syndrome (CBS), including Alzheimer's disease (AD). Dopamine transporter density imaging with Ioflupane 123 I SPECT (DaTscan) may be normal in CBS. No studies to date have examined the relationship between DaTscan status and underlying pathology in CBS. OBJECTIVES: The main objective of the study was to test whether a normal DaTscan in CBS patients is indicative of an underlying AD pathology, as determined by cerebrospinal fluid (CSF) biomarkers. METHODS: Eighteen CBS patients were included. They were divided into patients with an AD and a non-AD disease pathology, based on their cerebrospinal fluid biochemical profile. A typical AD CSF profile was defined as an increase in total and phosphorylated at threonine 181 tau protein in addition to a decrease in amyloid-beta with 42 amino acids. DaTscan data were compared in these two groups. RESULTS: Eight of the 18 CBS patients (44%) had a normal DaTscan. Seven of the 18 CBS patients (39%) had an AD cerebrospinal fluid biochemical profile. Two of seven CBS patients with AD biomarker profile had abnormal DaTscans. Three of 11 CBS patients with a non-AD biomarker profile had normal DaTscans. A normal DaTscan was indicative of AD pathology with suboptimal (~70%) sensitivity and specificity. Semi-quantitative DaTscan analysis did not differentiate between AD from non-AD CSF biomarker profile in CBS. CONCLUSION: A normal DaTscan is indicative of AD in CBS, but the sensitivity and specificity of DaTscan as an in vivo marker of AD pathology is suboptimal.

Initial Data and a Clinical Diagnosis Transition for the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) Study.

Background and Objectives: This article presents data from the ongoing Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study (ALBION) regarding baseline clinical characterizations and CSF biomarker profiles, as well as preliminary longitudinal data on clinical progression. Materials and Methods: As of March 2022, 138 participants who either were cognitively normal (CN, n = 99) or had a diagnosis of mild cognitive impairment (MCI, n = 39) had been recruited at the specialist cognitive disorders outpatient clinic at Aiginition Hospital. Clinical characteristics at baseline were provided. These patients were followed annually to determine progression from CN to MCI or even dementia. CSF biomarker data (amyloid ß1-42, phosphorylated tau at threonine 181, and total tau) collected using automated Elecsys® assays (Roche Diagnostics) were available for 74 patients. These patients were further sorted based on the AT(N) classification model, as determined by CSF Aß42 (A), CSF pTau (T), and CSF tTau (N). Results: Of the 49 CN patients with CSF biomarker data, 21 (43%) were classified as exhibiting "Alzheimer's pathologic change" (A+Τ− (Ν)−) and 6 (12%) as having "Alzheimer's disease" (A+T−(N)+, A+T+(N)−, or A+T+(N)+). Of the 25 MCI patients, 8 (32%) displayed "Alzheimer's pathologic change", and 6 (24%) had "Alzheimer's disease". A total of 66 individuals had a mean follow-up of 2.1 years (SD = 0.9, min = 0.8, max = 3.9), and 15 of those individuals (22%) showed a clinical progression (defined as a worsening clinical classification, i.e., from CN to MCI or dementia or from MCI to dementia). Overall, participants with the "AD continuum" AT(N) biomarker profile (i.e., A+T−(N)−, A+T−(N)+, A+T+(N)−, and A+T+(N)+) were more likely to clinically progress (p = 0.04). Conclusions: A CSF "AD continuum" AT(N) biomarker profile is associated with an increased risk of future clinical decline in CN or MCI subjects.

Silent Pauses and Speech Indices as Biomarkers for Primary Progressive Aphasia.

Background and Objectives: Recent studies highlight the importance of investigating biomarkers for diagnosing and classifying patients with primary progressive aphasia (PPA). Even though there is ongoing research on pathophysiological indices in this field, the use of behavioral variables, and especially speech-derived factors, has drawn little attention in the relevant literature. The present study aims to investigate the possible utility of speech-derived indices, particularly silent pauses, as biomarkers for primary progressive aphasia (PPA). Materials and Methods: We recruited 22 PPA patients and 17 healthy controls, from whom we obtained speech samples based on two elicitation tasks, i.e., cookie theft picture description (CTP) and the patients' personal narration of the disease onset and course. Results: Four main indices were derived from these speech samples: speech rate, articulation rate, pause frequency, and pause duration. In order to investigate whether these indices could be used to discriminate between the four groups of participants (healthy individuals and the three patient subgroups corresponding to the three variants of PPA), we conducted three sets of analyses: a series of ANOVAs, two principal component analyses (PCAs), and two hierarchical cluster analyses (HCAs). The ANOVAs revealed significant differences between the four subgroups for all four variables, with the CTP results being more robust. The subsequent PCAs and HCAs were in accordance with the initial statistical comparisons, revealing that the speech-derived indices for CTP provided a clearer classification and were especially useful for distinguishing the non-fluent variant from healthy participants as well as from the two other PPA taxonomic categories. Conclusions: In sum, we argue that speech-derived indices, and especially silent pauses, could be used as complementary biomarkers to efficiently discriminate between PPA and healthy speakers, as well as between the three variants of the disease.

Lentiform fork sign in a patient with systemic lupus erythematosus.

The "lentiform fork sign" is a rare MRI sign which affects the posterior limb of the internal capsule, the external capsule, and extends posteriorly to form a fork-like appearance. It has been reported exclusively in disorders with metabolic acidosis, such as uremic encephalopathy, mitochondrial disorders, methanol/ethylene glycol intoxication, etc. It is considered to represent vasogenic edema and is often reversible. We describe a 73-year old female with a 2-month history of rapidly deteriorating imbalance, bradykinesia, confusion, and disorientation. At examination, she was encephalopathic. She had a pyramidal and rigid-akinetic parkinsonian syndrome, with signs of polyneuropathy. MRI revealed the "lentiform fork sign". She exhibited a high ANA titer, positive anti-dsDNA, anti-ENA, and anti-ß2GPI-IgM antibodies, as well as positive cerebrospinal fluid IgG and albumin indices. No metabolic acidosis was recorded. A diagnosis of systemic lupus erythematosus (SLE) was established. She was treated initially with methylprednisolone, followed by hydroxychloroquine, with complete remission of her symptoms and disappearance of the "lentiform fork sign". We present a case of a patient with SLE, harboring the "lentiform fork sign", in the absence of metabolic acidosis. Differential diagnosis of the "lentiform fork sign" should be expanded to include autoimmune disorders, even in the absence of metabolic acidosis.

Midbrain morphology in idiopathic normal pressure hydrocephalus: A progressive supranuclear palsy mimic.

INTRODUCTION: Various MRI markers have been applied to support the diagnosis of progressive supranuclear palsy (PSP), such as midbrain diameter and surface, superior cerebellar peduncle (SCP) width, midbrain to pons (m/p) diameter and surface ratio and the Magnetic Resonance Parkinsonism Index (MRPI). These markers provide excellent diagnostic accuracy in discriminating Richardson's syndrome from other causes of Parkinsonism. Idiopathic normal pressure hydrocephalus (iNPH) may mimic Richardson's syndrome, particularly in cases of subtle opthalmokinetic abnormalities. The aim of this study was to compare these MRI markers in PSP and iNPH and examine their diagnostic accuracy. MATERIALS AND METHODS: Forty-three patients with probable PSP, 17 patients with iNPH, and 29 controls were included. Midbrain diameter and surface, SCP width, m/p diameter and surface ratio and the MRPI were recorded. The "hummingbird sign," "morning glory sign" and "mickey mouse sign" were also evaluated. Analysis of covariance, chi-squared test, and ROC curve analysis were used as appropriate. RESULTS: All MRI measurements differed significantly among the three study groups. Comparison of PSP and iNPH patients produced the following significant differences: midbrain diameter (P < .0001), m/p diameter ratio (P < .0001), SCP width (P = .050), and MRPI (P = .049). None of these markers produced combined high (>80%) specificity and sensitivity. Qualitative MRI signs were specific, but lacked sensitivity. DISCUSSION: Midbrain morphology in iNPH may resemble that of PSP. Established MRI markers of midbrain and SCP atrophy cannot confidently differentiate PSP from iNPH. MRI markers do not provide combined high sensitivity and specificity for the differential diagnosis of PSP from iNPH.

In vivo Prevalence of Alzheimer Biomarkers in Dementia with Lewy Bodies.

BACKGROUND: Neuropathological studies indicate concomitant Alzheimer's disease (AD) pathology in patients with dementia with Lewy bodies (DLB). OBJECTIVES: To measure cerebrospinal fluid (CSF) levels of ß-amyloid peptide with 42 amino acids (Aß42), total tau protein (τT), and tau phosphorylated at threonine 181 (τP-181) in 38 patients fulfilling the diagnostic criteria of probable DLB according to the most recent (4th consensus) report. METHODS: Double-sandwich commercial ELISAs (Innotest; Fujirebio, Gent, Belgium) were used for measurements. RESULTS: According to the current cutoff values of our laboratory, 4 biomarker profiles were noted: abnormal levels of Aß42 only (44.7%), full AD profile (39.5%), abnormal levels of τT only (5.3%), and normal levels of all 3 biomarkers (10.5%). AD profile was associated with female sex, older age, lower education, and lower MMSE scores. CONCLUSIONS: Reduction in Αß42 in DLB may be more common (>80% of patients) than previously thought, and ∼40% may have the typical CSF AD biomarker profile. AD biochemistry in DLB may be an evolving process showing increasing frequency with disease progression.

Anti-NMDA receptor encephalitis presenting as isolated aphasia in an adult.

Anti-NMDA receptor (NMDA-r) encephalitis is a relatively rare cause of autoimmune encephalitis with divergent clinical presentations. We report a case of an adult patient with anti-NMDA-r encephalitis presenting with isolated, abrupt-onset aphasia. Her condition remained unaltered over a period of 6 months. The patients' electroencephalogram findings were typical for NMDA-r encephalitis; however, her magnetic resonance imaging and cerebrospinal fluid analysis were normal. She responded well to immunotherapy, and aphasia eventually resolved. The natural course of the present case contradicts the rapidly progressive nature of typical NMDA-r encephalitis. Furthermore, it broadens the clinical spectrum of anti-NMDA-r encephalitis, to incorporate isolated, nonprogressive aphasia.

Simple linear brainstem MRI measurements in the differential diagnosis of progressive supranuclear palsy from the parkinsonian variant of multiple system atrophy.

Differential diagnosis of progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) can be difficult, particularly in atypical cases or early in the disease course. The Magnetic Resonance Parkinsonism Index (MRPI) utilizes linear and surface (planimetry) measurements and has been proposed as a dual MRI biomarker, with high values indicative of PSP and low values of MSA. The aim of this study was to examine the utility of simple linear MRI brainstem measurements, without the use of MRI planimetry, in the diagnosis of patients with Parkinsonism and compare them to the MRPI. A total of 51 patients (PSP: 24, MSA-P: 9, PD: 18) and 15 healthy controls were included. Simple linear MRI distances of brainstem structures were measured. These included midbrain and pons diameters as well as superior cerebellar peduncle (SCP) and middle cerebellar peduncle (MCP) widths. All relevant indices, including ratios and products, were also calculated. The SCP by midbrain product (SCP × midbrain) provided improved sensitivity (100 vs. 91%) and identical specificity (98%) for the diagnosis of PSP, compared to the MRPI. Neither the MRPI nor any of the linear measurements were able to discriminate MSA-P from PD. The SCP by midbrain product is a novel, potent MRI biomarker for PSP.

Recognition of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) in Two Oligosymptomatic Sisters with Low CADASIL Scale Scores and a Venous Dysplasia: Report of a Novel Greek Family.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) due to mutations of the NOTCH3 gene is the most common cause of inherited cerebral small-vessel disease and one of the genetic causes of migraine with aura. The so-called CADASIL scale has been proposed as a clinical screening tool, and a score of 15 or higher seems useful in identifying patients with high probability of carrying NOTCH3 mutations. We studied a novel Greek family with clinical features compatible with CADASIL. Genetic analysis of NOTCH3 in the 2 living patients revealed the R182C mutation. Both patients had low scores (12 and 14) in the CADASIL scale, probably due to their relatively young age (38 and 37 years, respectively) at which cognitive decline and external capsule involvement have not developed yet. Another unusual feature in the second patient was a venous dysplasia in the parietal lobe. Observations presented here add to the notion that the CADASIL scale, although useful, probably needs a revision, taking into account the patient's age at which the score is calculated.

Cerebrospinal Fluid TAR DNA-Binding Protein 43 Combined with Tau Proteins as a Candidate Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Spectrum Disorders.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are nowadays recognized as spectrum disorders with a molecular link, the TAR DNA-binding protein 43 (TDP-43), rendering it a surrogate biomarker for these disorders. METHODS: We measured cerebrospinal fluid (CSF) levels of TDP-43, beta-amyloid peptide with 42 amino acids (Aß42), total tau protein (τT), and tau protein phosphorylated at threonine 181 (τP-181) in 32 patients with ALS, 51 patients with FTD, and 17 healthy controls. Double-sandwich commercial enzyme-linked immunosorbent assays were used for measurements. RESULTS: Both ALS and FTD patients presented with higher TDP-43 and τT levels compared to the control group. The combination of biomarkers in the form of the TDP-43 × τT / τP-181 formula achieved the best discrimination between ALS or FTD and controls, with sensitivities and specificities >0.8. CONCLUSION: Combined analysis of TDP-43, τT, and τP-181 in CSF may be useful for the antemortem diagnosis of ALS and FTD.

Cerebrospinal Fluid Total, Phosphorylated and Oligomeric A-Synuclein in Parkinson's Disease: A Systematic Review, Meta-Analysis and Meta-Regression Study.

Background: The diagnostic accuracy for Parkinson's disease (PD), a synucleinopathy, based on diagnostic criteria is suboptimal. A biomarker for synucleinopathies is pivotal both from a clinical and from a research point of view. CSF a-synuclein has been extensively studied over the past two decades as a candidate biomarker of synucleinopathies. Herein, we present data on studies focusing on total, phosphorylated and oligomeric CSF a-synuclein in PD. Methods: Pubmed, Scopus and Web of Science were searched for studies with >10 PD patients and control subjects, with data (mean, SD) on total, phosphorylated or oligomeric a-synuclein. Cohen's d, as a measure of effect size, was calculated for all a-synuclein forms. Subgroup analysis and meta-regression were performed in an effort to explain between-study heterogeneity. Results: Thirty studies on total, six studies on oligomeric and one study on phosphorylated a-synuclein were included. Total a-synuclein was decreased and oligomeric a-synuclein increased in PD patients vs. controls. The effect size was medium for total and high for oligomeric a-synuclein. A-syn forms provided suboptimal combined sensitivity/specificity for the differentiation of PD from controls. There was significant between-study heterogeneity. The PD cohort characteristics (sex, age, disease duration, UPDRS, H & Y) and study characteristics (study design, healthy vs. neurological controls, control for CSF blood contamination, method of a-syn measurement) could not account for between-study heterogeneity. Publication bias was limited. Conclusions: CSF a-synuclein levels lack sufficient accuracy to be used as biomarkers for PD. The standardization of (pre)analytical variables may improve the discriminatory power of a-synuclein forms in the future.

Cerebrospinal Fluid Total and Phosphorylated Tau Protein in Behavioral Variant Frontotemporal Dementia, Progressive Supranuclear Palsy, Corticobasal Syndrome and Non-Fluent Agrammatic Primary Progressive Aphasia: A Systematic Review and Meta-Analysis.

(1) Background: Frontotemporal lobar degeneration (FTLD) is a generic term which refers to multiple pathologies, including FTLD-tau. The most common FTLD-tau diseases are Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). These diseases share four major syndromes: behavioral variant frontotemporal dementia (bvFD), Richardson syndrome (RS), corticobasal syndrome (CBS) and non-fluent agrammatic primary progressive aphasia (nfa-PPA). The primary aim of this meta-analysis was to examine the diagnostic performance of CSF total (t-tau) and phosphorylated (p-tau) protein in bvFTD, RS, CBS, nfa-PPA and pathologically or genetically defined tauopathy. (2) Methods: A systematic review and meta-analysis was performed on all studies with >10 subjects in a bvFTD/RS/CBS/nfa-PPA group and control group and available data on CSF t-tau or p-tau (mean, SD). Cohen's d was used to quantify the effect size of each study (3) Results: The PSP/tauopathy patients exhibited decreased levels of CSF p-tau compared to the control subjects. The CBS/bvFTD/nfa-PPA cohorts exhibited an increase in t-tau compared to the control groups. (4) Conclusions: Tauopathies may exhibit an inherent decrease in CSF p-tau. The admixture of AD patients in FTD cohorts and high heterogeneity among studies on rare diseases are significant confounding factors in FTLD studies.

In Vivo Prevalence of Beta-Amyloid Pathology and Alzheimer's Disease Co-Pathology in Idiopathic Normal-Pressure Hydrocephalus-Association with Neuropsychological Features.

Idiopathic normal-pressure hydrocephalus (iNPH) is a clinic-radiological neurological syndrome presenting with cognitive deficits, gait disturbances and urinary incontinence. It often coexists with Alzheimer's disease (AD). Due to the reversible nature of iNPH when promptly treated, a lot of studies have focused on possible biomarkers, among which are cerebrospinal fluid (CSF) biomarkers. The aim of the present study was to determine the rate of beta-amyloid pathology and AD co-pathology by measuring AD CSF biomarkers, namely, amyloid beta with 42 and 40 amino acids (Aß42), the Aß42/Aß40 ratio, total Tau protein (t-Tau) and phosphorylated Tau protein at threonine 181 (p-Tau), in a cohort of iNPH patients, as well as to investigate the possible associations among CSF biomarkers and iNPH neuropsychological profiles. Fifty-three patients with iNPH were included in the present study. CSF Aß42, Aß40, t-Tau and p-Tau were measured in duplicate with double-sandwich ELISA assays. The neuropsychological evaluation consisted of the Mini-Mental State Examination, Frontal Assessment Battery, Five-Word Test and CLOX drawing tests 1 and 2. After statistical analysis, we found that amyloid pathology and AD co-pathology are rather common in iNPH patients and that higher values of t-Tau and p-Tau CSF levels, as well as the existence of the AD CSF profile, are associated with more severe memory impairment in the study patients. In conclusion, our study has confirmed that amyloid pathology and AD-co-pathology are rather common in iNPH patients and that CSF markers of AD pathology and t-Tau are associated with a worse memory decline in these patients.