Selective Reminding Test Research Articles

Differentiating between Alzheimer's Disease and Vascular Cognitive Impairment: Is the "Memory Versus Executive Function" Contrast Still Relevant?

The contrast between memory versus executive function impairments is commonly used to differentiate between neurocognitive disorders (NCDs) due to Alzheimer's disease (AD) and vascular cognitive impairment (VCI). We reconsidered this question because of the current use of AD biomarkers and the recent revision of the criteria for AD, VCI, and dysexecutive syndrome. To establish and compare the neuropsychological profiles in AD (i.e., with positive CSF biomarkers) and in VCI. We included 62 patients with mild or major NCDs due to pure AD (with positive CSF biomarker assays), and 174 patients (from the GRECogVASC cohort) with pure VCI. The neuropsychological profiles were compared after stratification for disease severity (mild or major NCD). We defined a memory-executive function index (the mean z score for the third free recall and the delayed free recall in the Free and Cued Selective Reminding Test minus the mean z score for category fluency and the completion time in the Trail Making Test part B) and determined its diagnostic accuracy. Compared with VCI patients, patients with AD had significantly greater memory impairments (p = 0.001). Executive function was impaired to a similar extent in the two groups (p = 0.11). Behavioral executive disorders were more prominent in the AD group (p = 0.001). Although the two groups differed significant with regard to the memory-executive function index (p < 0.001), the latter's diagnostic accuracy was only moderate (sensitivity: 63%, specificity: 87%). Although the contrast between memory and executive function impairments was supported at the group level it does not reliably discriminate between AD and VCI at the individual level.

Relationship between Hippocampal Subfields and Category Cued Recall in AD and PDD: A Multimodal MRI Study

Alzheimer’s disease (AD) and Parkinson’s disease with dementia (PDD) are characterized by a different mnesic failure, particularly in memory cued recall. Although hippocampal involvement has been shown in both these diseases, it remains unknown whether a selective damage of specific subfields within the hippocampus may be responsible for the peculiar mnesic profile observed in AD and PDD. To explore this topic, we combined a multimodal 3 T-MRI hippocampal evaluation (whole-brain T1-weighted and diffusion tensor imaging) with a hippocampal-targeted neuropsychological assessment (Free and Cued Selective Reminding Test [FCSRT]) in 22 AD subjects, 18 PDD and 17 healthy controls. Macro- and microstructural features (volume; shape; mean diffusivity [MD]; fractional anisotropy [FA]) of bilateral hippocampi (whole and subfields) were obtained. Correlations between MRI-derived parameters and neuropsychological evaluations were performed.In the comparison between AD and PDD, the multimodal analysis allowed us to identify that subiculum, CA1 and CA4-DG were differently involved in these diseases and correlated with immediate and delayed total recall items of FCSRT. Moreover, compared to controls, AD showed a reduction in almost all subfields, with a MD increase in the same regions, whereas PDD displayed a volume loss, less severe than AD, more evident in the CA2-3 and presubiculum subfields.Our study provides new evidence that hippocampal subregions had different vulnerability to damage related to AD and PDD. The combination of the in vivo analysis of hippocampal subfields with the FCSRT paradigm provided important insights into whether changes within specific hippocampal subfields are related to the different mnesic profile in AD and PDD patients.

Neuroanatomical Comparison of the "Word" and "Picture" Versions of the Free and Cued Selective Reminding Test in Alzheimer's Disease.

Episodic memory tests with cued recall, such as the Free and Cued Selective Reminding Test (FCSRT), allow for the delineation of hippocampal and prefrontal atrophy contributions to memory performance in Alzheimer's disease (AD). Both Word and Picture versions of the test exist but show different profiles, with the Picture version usually scoring higher across different cohorts. One possible explanation for this divergent performance between the different modality versions of the test might be that they rely on different sets of neural correlates. The current study explores this by contrasting the neural correlates of the Word and Picture versions of the FCSRT with voxel-based morphometry (VBM) in AD and healthy subjects. We predicted that the Picture version would be associated with different cortical regions than the Word version, which might be more hippocampal-centric. When comparing 35 AD patients and 34 controls, AD patients exhibited impairments on both versions of the FCSRT and both groups performed higher in the Picture version. A region of interest analysis based on prior work revealed significant correlations between free recall of either version with atrophy of the temporal pole and hippocampal regions. Thus, contrary to expectations, performance on both the Word and the Picture version of the FCSRT is associated with largely overlapping networks. Free recall is associated with hippocampal volume and might be properly considered as an indicator of hippocampal structural integrity.

Cognitive impairment and quality of life of people with epilepsy and neurocysticercosis in Zambia

Cognitive impairment and quality of life (Qol) are important to assess the burden of epilepsy and neurocysticercosis (NCC), which are common but neglected in Sub-Saharan Africa (SSA). The aims of this study were to assess cognitive performance and Qol of people with epilepsy (PWE) in Zambia and to explore differences in PWE with and without NCC.In this community based, cross-sectional case-control-study, 47 PWE and 50 healthy controls completed five neuropsychological tests (Mini Mental State Examination (MMSE), Digit Span, Selective Reminding Test (SRT), Spatial Recall Test (SPART), Test Battery of Attentional Performance (TAP)) and a World Health Organization (WHO) questionnaire of Qol. Comparisons were made between PWE (n=47) and healthy controls (n=50) and between PWE with NCC (n=28) and without NCC (n=19), respectively, using Analysis of Covariance (ANCOVA) and Linear Models (LMs) while correcting for confounders such as age, sex, and schooling years, and adjusting for multiplicity.Working memory, spatial memory, verbal memory, verbal learning, orientation, speech and language reception, visuoconstructive ability, and attentional performance were significantly reduced in PWE compared with healthy controls (ANCOVA and LM, p<0.05). Quality of life of PWE was significantly lower in three domains (psychological, social, environmental) and in overall Qol compared with healthy controls (ANCOVA, p<0.05). There were no significant differences between PWE with NCC and PWE without NCC detected by ANCOVA. Using LM, significant differences between the groups were detected in four tests, indicating worse performance of PWE without NCC in MMSE, Digit Span, SPART, and lower physical Qol.Epilepsy was found to be associated with cognitive impairment and reduced Qol. People with epilepsy due to NCC had similar cognitive impairment and Qol compared with PWE due to other causes. Further studies should investigate the role of different conditions of NCC and the role of seizures on cognition and Qol.

Word and Picture Version of the Free and Cued Selective Reminding Test (FCSRT): Is There Any Difference?

The Free and Cued Selective Reminding Test (FCSRT) is the most commonly used neuropsychological test to evaluate episodic memory. Two variants of FCSRT exist, using the recall of words (FCSRT-w) or pictures (FCSRT-p). Fourteen patients with mild cognitive impairment underwent neuropsychological evaluation and brain magnetic resonance. We found differences in FCSRT-w and FCSRT-p variants scores. FCSRT-p was correlated with atrophy in areas involved in visual stimuli processing while FCSRT-w was correlated to hippocampal atrophy. Our study suggests that FCSRT-w and FCSRT-p scores are not equivalent, but a larger cohort of patients is needed to validate these results.

Comparison between FCSRT and LASSI-L to Detect Early Stage Alzheimer's Disease.

The Free and Cued Selective Reminding Test (FCSRT) is the most accurate test for the diagnosis of prodromal Alzheimer's disease (AD). Recently, a novel cognitive test, the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), has been developed in order to provide an early diagnosis. To compare the diagnostic accuracy of the FCSRT and the LASSI-L for the diagnosis of AD in its preclinical and prodromal stages using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a reference. Fifty patients consulting for subjective memory complaints without functional impairment and at risk for AD were enrolled and evaluated using FCSRT, LASSI-L, and FDG-PET. Participants were evaluated using a comprehensive neurological and neuropsychological protocol and were assessed with the FCSRT and LASSI-L. FDG-PET was acquired concomitantly and used for classification of patients as AD or non-AD according to brain metabolism using both visual and semi-quantitative methods. LASSI-L scores allowed a better classification of patients as AD/non-AD in comparison to FCSRT. Logistic regression analysis showed delayed recall and failure to recovery from proactive semantic interference from LASSI-L as independent statistically significant predictors, obtaining an area under the curve of 0.894. This area under the curve provided a better discrimination than the best FCSRT score (total delayed recall, area under the curve 0.708, p = 0.029). The LASSI-L, a cognitive stress test, was superior to FCSRT in the prediction of AD features on FDG-PET. This emphasizes the possibility to advance toward an earlier diagnosis of AD from a clinical perspective.

Change in Odor Identification Impairment is Associated with Improvement with Cholinesterase Inhibitor Treatment in Mild Cognitive Impairment.

Anticholinergic challenge can induce odor identification impairment that indicates Alzheimer's disease pathology. To determine if decline in odor identification ability with anticholinergic challenge can predict improvement with donepezil, a cholinesterase inhibitor (ChEI), in patients with mild cognitive impairment (MCI). At baseline, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Donepezil was started at 5 mg daily, increased to 10 mg daily if tolerated, and then the dose was kept constant for 52 weeks. Main outcomes were change in Selective Reminding Test (SRT) total immediate recall and ADAS-Cog total score from baseline to 26 and 52 weeks. In 37 participants, mean age 70.4 (SD 9.8) y, greater atropine-induced decrease in UPSIT score at baseline was associated with greater improvement in SRT total recall score from baseline to 26 and 52 weeks (p < 0.03). This effect remained after adjusting for time, age, education, gender, APOE ɛ4 status, and baseline cognitive score (p < 0.05). Decrease in UPSIT score was associated with global improvement (CIBIC-plus) over 52 weeks (p < 0.02). After excluding patients with congential anosmia, increase in UPSIT score from 0 to 8 weeks showed a trend-level association with improvement on the ADAS-Cog (p = 0.07). Anticholinergic challenge-induced odor identification decline was associated with cognitive improvement, and short-term improvement in odor identification tended to predict longer term cognitive improvement. These simple inexpensive strategies have the potential to improve selection of patients with MCI for ChEI treatment.

Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial

Because curcumin's anti-inflammatory properties may protect the brain from neurodegeneration, we studied its effect on memory in non-demented adults and explored its impact on brain amyloid and tau accumulation using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography (FDDNP-PET). Forty subjects (age 51-84 years) were randomized to a bioavailable form of curcumin (Theracurmin® containing 90 mg of curcumin twice daily [N = 21]) or placebo (N = 19) for 18 months. Primary outcomes were verbal (Buschke Selective Reminding Test [SRT]) and visual (Brief Visual Memory Test-Revised [BVMT-R]) memory, and attention (Trail Making A) was a secondary outcome. FDDNP-PET signals (15 curcumin, 15 placebo) were determined in amygdala, hypothalamus, medial and lateral temporal, posterior cingulate, parietal, frontal, and motor (reference) regions. Mixed effects general linear models controlling for age and education, and effect sizes (ES; Cohen's d) were estimated. SRT Consistent Long-Term Retrieval improved with curcumin (ES = 0.63, p = 0.002) but not with placebo (ES = 0.06, p = 0.8; between-group: ES = 0.68, p = 0.05). Curcumin also improved SRT Total (ES = 0.53, p = 0.002), visual memory (BVMT-R Recall: ES = 0.50, p = 0.01; BVMT-R Delay: ES = 0.51, p = 0.006), and attention (ES = 0.96, p < 0.0001) compared with placebo (ES = 0.28, p = 0.1; between-group: ES = 0.67, p = 0.04). FDDNP binding decreased significantly in the amygdala with curcumin (ES = -0.41, p = 0.04) compared with placebo (ES = 0.08, p = 0.6; between-group: ES = 0.48, p = 0.07). In the hypothalamus, FDDNP binding did not change with curcumin (ES = -0.30, p = 0.2), but increased with placebo (ES = 0.26, p = 0.05; between-group: ES = 0.55, p = 0.02). Daily oral Theracurmin may lead to improved memory and attention in non-demented adults. The FDDNP-PET findings suggest that symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory.

Adaptation and standardization of the free and cued selective reminding test to the Moroccan population

Adaptation and standardization of the free and cued selective reminding test to the Moroccan population

Free and cued selective reminding test (FCSRT): A Tunisian normative study

Background: The FCSRT is a memory test, that’s often considered to be essential in the neuropsychological examination of elderly people, used to detect episodic memory deficits.

Study of memory deficit in Alzheimer's disease by means of complexity analysis of fNIRS signal.

Working memory deficit is a signature of Alzheimer's disease (AD). The free and cued selective reminding test (FCSRT) is a clinical test that quantifies memory deficit for AD diagnosis. However, the diagnostic accuracy of FCSRT may be increased by accompanying it with neuroimaging. Since the test requires doctor-patient interaction, brain monitoring is challenging. Functional near-infrared spectroscopy (fNIRS) could be suited for such a purpose because of the fNIRS flexibility. We investigated whether the complexity, based on sample entropy and multiscale entropy metrics, of the fNIRS signal during FCSRT was correlated with memory deficit in early AD. fNIRS signals were recorded over the prefrontal cortex of healthy and early AD participants. Group differences were tested through Wilcoxon-Mann-Whitney test ([Formula: see text]). At group level, we found significant differences for Brodmann areas 9 and 46. The results, although preliminary, demonstrate the feasibility of performing ecological studies on early AD with fNIRS. This approach may provide a potential neuroimaging-based method for diagnosis of early AD, viable at the doctor's office level, improving test-based diagnosis. The increased entropy of the fNIRS signal in early AD suggests the opportunity for further research on the neurophysiological status in AD and its relevance for clinical symptoms.

Comparison of the Buschke Selective Reminding Test and the California Verbal Learning Test – Second Edition in a heterogeneous sample of people with traumatic brain injury

ABSTRACTThis study examined score and classification differences between the Buschke Selective Reminding Test (SRT) and the California Verbal Learning Test - Second Edition (CVLT-II) in a TBI sample. Seventy-nine participants with traumatic brain injury (TBI) were included and were comprised of 49 mild TBI, 11 moderate TBI, and 14 severe TBI. The majority of participants with mild TBI were involved in litigation. Scores were compared between the CVLT-II and SRT on the total sample and after segregating TBI severity. Correlations between the SRT and CVLT-II were variable (r = .23 to .72). Total List score was lower on the SRT across all levels of TBI severity (p < .006). Learning score was lower on the SRT in mild and severe TBI groups (p < .006). Long delay free recall score was lower on the SRT in mild TBI group only (p < .006). Across TBI severity, lower scores were found on the CVLT-II between severe and mild TBI (p = .04). Scores on the SRT did not differ between TBI severities. The two tests appear to provide different clinical interpretations in a TBI sample. Results may be due to features of the normative data, test procedures, and/or word lists. Clinical implications and limitations are discussed.

The Utility of the Cognitive Function Instrument (CFI) to Detect Cognitive Decline in Non-Demented Older Adults.

Subjective cognitive complaint is a sensitive marker of decline. This study aimed to (1) examine reliability of subjective cognitive complaint using the Cognitive Function Instrument (CFI), and (2) assess the utility of the CFI to detect cognitive decline in non-demented elders. Data from a four-year longitudinal study at multiple Alzheimer's Disease Cooperative Study (ADCS) sites were extracted (n = 644). Of these, 497 had Clinical Dementia Rating (CDR) global scores of 0 and 147 had a CDR of 0.5. Mean age and education were 79.5±3.6 and 15.0±3.1 years, respectively. All participants and their study partners completed the subject and study partner CFI yearly. Modified Mini-Mental State Exam (mMMSE) and Free and Cued Selective Reminding Test (FCSRT) were administered. Scores below the predetermined cut-off scores on either measure at annual visit were triggers for a full diagnostic evaluation. Cognitive decline was defined by the absence/presence of the trigger. Three-month test retest reliability showed that inter-class coefficients for subject and study partner CFI were 0.76 and 0.78, respectively. Generalized estimating equation method revealed that both subject and study partner CFI change scores and scores from previous year were sensitive to cognitive decline in the CDR 0 group (p < 0.05). In the CDR 0.5 group, only the study partner CFI change score predicted cognitive decline (p < 0.05). Cognitive decline was predicted differentially by CDR level with subject CFI scores providing the best prediction for those with CDR 0 while study partner CFI predicted best for those at CDR 0.5.

Long-term forgetting in patients with traumatic brain injury

Verbal memory impairment has been described in patients with traumatic brain injury (TBI) but the specific altered process, between encoding, consolidation and retrieval, is still discussed. The aim of this study was to use new measures to detect verbal memory impairment in TBI patients. In this purpose, we analyzed encoding and consolidation processes as a function of each patient's performance during a memory test. We calculated a learning score and a percentage of forgetfulness. One-week Free and Cued Selective Reminding Test (1W-FCSRT), which special feature relies on a 30-minutes and a one-week-delayed recall after encoding, was administered to 98 TBI patients (age range at the time of assessment from 20 to 56 years). Their performance was compared to performance of neurologically healthy volunteers matched for age, gender and socio-cultural level. A statistically significant difference was found between TBI patients and healthy volunteers for the learning score (W = 7640.5, P < .001). Indeed, TBI patients (M = 31.45, SD = 35.32) performed worse than the healthy volunteers (M = 51.62, SD = 27.78). Percentage of forgetfulness in TBI patients was above healthy volunteers’ performance and increased with the delay between encoding and retrieval ( P < .001). Our results underlined an altered encoding and a long-term consolidation impairment in TBI patients. It is crucial to detect these deficits to propose a better professional rehabilitation.

The TMA-93: A New Memory Test for Alzheimer's Disease in Illiterate and Less Educated People.

The present study aimed at validating the Memory Associative Test of the district of Seine-Saint-Denis (TMA)-93, a new test of episodic memory. The TMA-93 was proposed to mostly less educated and multicultural elderly population composed of 376 healthy controls (HC) and 94 patients with Alzheimer's disease (AD). The construct validity was checked by studying correlations with a widely used memory test (the Free and Cued Selective Reminding Test [FCSRT]) in the subsample of literate patients. Results showed that (i) all the TMA-93 scores of the patients with AD were lower than those of the HC, (ii) the TMA-93 total score identified patients with AD with a high sensitivity (88%) and very high specificity (97%), and (iii) the TMA-93 total score was strongly correlated with both free recall and total recall scores of the FCSRT. Taken together, results showed that the TMA-93 is a reliable tool to assess episodic memory in a multicultural, less educated, or illiterate population, with good construct validity for AD diagnostic accuracy.

The impact of chronic psychiatric disorders on cognitive decline.

Based on seemingly contradictory results in the existing literature, the objective of our study was to investigate whether older individuals suffering from chronic psychiatric disorders show a more rapid decline in cognitive performances than their non-psychiatric counterparts, or if the pattern of decline through older age is similar in both groups. A total of 820 older adults were selected from the Ageing Multidisciplinary Investigation (AMI) cohort study, which studies health-related issues of people over 65 years old living in rural areas. Among them, 30 suffer from chronic psychiatric disorders. Cognition was assessed with four neuropsychological tests: the Mini-Mental State Examination, the Digit Symbol Substitution Test, the Free and Cued Selective Reminding test and the Isaacs Set Test. Linear mixed models were used to compare the evolution of cognitive performances in the two groups between baseline and the four-year follow-up. Despite lower performances at baseline, the pattern of cognitive decline of the psychiatric group is similar to that of the control group. As suggested by this study conducted in rural communities, community-dwelling people suffering from chronic psychiatric disorders should not be considered at greater risk of age-related accelerated cognitive decline than the non-psychiatric older population.

NEUROIMAGING BIOMARKERS OF THE A/T/N CLASSIFICATION SYSTEM PREDICT CROSS-SECTIONAL AND LONGITUDINAL CHANGE IN PRECLINICAL AND EARLY ALZHEIMER DISEASE

Assessment of β-amyloid (A), tau (T) and neurodegeneration (N) biomarkers has recently been proposed by Jack and colleagues (2016, Neurology) to stage Alzheimer disease (AD). In isolation, biomarkers for A/T/N have shown associations with cognitive changes in the preclinical and early symptomatic stages of AD. However, the relative contribution of each A/T/N imaging biomarker to cross-sectional cognitive impairment and longitudinal decline has not been well-characterized. The current study assesses unique variance in cross-sectional and longitudinal cognition explained by each neuroimaging biomarker. Cognitive data were available on 104 individuals from an average of 5 assessments over an average 6-year period. All participants had a [18F]AV-1451 (T807, flortaucipir) tau PET scan during follow-up and both a [18F]-AV-45 b-amyloid scan and hippocampal volume from a structural MRI within one year from the tau scan. Unique variance explained (measured with R2) by cross-sectional imaging biomarkers in both cross-sectional and longitudinal performance on the Free and Cued Selective Reminding Test (fcSRT) was calculated from linear regression models that included age, education, gender and Clinical Dementia Rating as covariates. Continuous variables were standardized prior to analysis. Cross-sectionally, tau PET significantly predicted a relatively large portion of the variance in fcSRT performance (ΔR2 = .13, beta = -1.38, p < .001). As expected, this relationship was much stronger in individuals at high risk for AD (Amyloid +) relative to low risk participants (Amyloid -). Neither amyloid (A) nor hippocampal volume (N) predicted cognition (ΔR2 < .01). Longitudinally, tau was again a significant predictor of decline (beta = -.08, ΔR2 = .03, p = .001) whereas both amyloid and hippocampal volume were not (ΔR2 < .01). Similar relationships between tau PET and cognitive decline were found in semantic memory (category fluency) and executive function (Trail Making B).

THE RELATIONSHIP BETWEEN CSF AMYLOID BETA CONCENTRATIONS AND FREE AND CUED RECALL PERFORMANCE AMONG PARTICIPANTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT

Alzheimer's Disease (AD) is a neurodegenerative disease which typically presents with a specific episodic memory impairment. Although accumulation of hypertphosphoryllated tau is held responsible for the neurodegeneration and hence the symptoms of AD, recent research suggests that changes in amyloid-β (Aβ) 1−42 concentrations might also be related to memory performance. We aimed to investigate whether cerebro-spinal fluid (CSF) Aβ42 concentrations are related to free and cued recall performance among a group of patients with amnestic type MCI. The results that will be presented here are part of a still ongoing research project. Currently, we have 18 participants diagnosed with amnestic type MCI. All participants underwent an extended procedure involving neurological examination, multimodal neuroimaging, neuropsychological assessment, and lumbar puncture for CSF biomarkers. Free and Cued Selective Reminding Test was used as the principal measure to assess memory performance. The CSF Aβ42 concentrations of the sample ranged between 299 and 1377 pg/mL. Based on their Aβ concentration, we assigned the sample into two groups: low Aβ group (n=9) and high Aβ group (n=9). The cutoff value was 850 pg/mL. Then, 2 groups were compared with regard to their FCSRT scores. Significant intergroup differences were found with regard to total free recall performance. Specifically, high-amyloid group had significantly higher total free recall scores than low amyloid group (U= 14.00, p<.05). On the other hand, with respect to cue index scores, which an indicator of how each participant is able to benefit from cues, there was not a statistically significant difference between the two groups. Our initial results suggest that reduced CSF Aβ42 concentrations might interfere with free recall performance. The fact that no significant relationship was found with regard to cued recall (which is a specific feature of AD amnesia) might suggest that Aβ42-related amnesia is different from tau-related one, which disconnects entorhinal cortex from the hippocampal formation initially and hence gives rise to typical amnesia (hippocampal-type) that does not improve with cuing. Functional disconnections due to Aβ42 accumulation within a larger network, such as default mode (DMN) is likely to underline such a non-hypocampal-type memory deficit.

PLACEBO-CONTROLLED TRIAL OF DONEPEZIL FOLLOWING ANTIDEPRESSANT TREATMENT IN PATIENTS WITH COMORBID DEPRESSION AND COGNITIVE IMPAIRMENT

In patients with comorbid depression and cognitive impairment, antidepressants are commonly used but the utility of cholinesterase inhibitors (CheI) as cognitive enhancers is not established. Eighty elderly (55–95 years old) depressed, cognitively impaired (DEP-CI) patients participated in the DOTCODE study at two sites: Columbia and Duke University Medical Centers. 40 of 79 patients who received antidepressant medication in the initial phase met criteria for amnestic mild cognitive impairment (MCI). After 16 weeks of open-label antidepressant treatment with antidepressants, primarily citalopram or venlafaxine, 61 patients were randomized to receive 62 weeks of the CheI donepezil 5–10 mg daily or placebo in a randomized, double-blind trial. Linear mixed effects models with random subject-specific intercepts were used to model ADAS-Cog13 and Selective Reminding Test (SRT) Total Immediate Recall over the course of the study. All models include baseline value of the outcome, age, study site, treatment, visit week, and the interaction between treatment and visit week (and interaction terms to test for moderators). In the first 16 weeks, depression improved in most patients and 39 of 61 randomized patients (64%) met responder criteria. In the 61 randomized patients, donepezil did not differ from placebo in change in the co-primary measures of ADAS-Cog13 (F=0.18, p=0.83) and SRT total recall (F=0.06, p=0.9). Four patients were diagnosed with probable Alzheimer's disease by end-trial. Apolipoprotein E e4 allele and MRI hippocampal volume were unrelated to differences in outcomes between donepezil and placebo. Periventricular hyperintensities (PVH) did not distinguish changes in cognition on donepezil from placebo on ADAS-Cog13 (F1,39 = 0.14, p = 0.71) but did on SRT total recall (F1,39 = 4.23, p = 0.04); less PVH was associated with greater improvement with donepezil on SRT total recall. In patients with comorbid depression and cognitive impairment, the addition of donepezil following antidepressant medication treatment did not improve cognition compared to placebo, though donepezil treatment was associated with better cognition in patients with less cerebrovascular disease. The findings add to those from studies in mild cognitive impairment without depression that have not demonstrated superiority for CheI over placebo in improving cognition.

ASSOCIATION OF PLASMA NEUROFILAMENT LIGHT CHAIN PROTEIN WITH BRAIN AMYLOID STATUS IN A PRECLINICAL COHORT OF SUBJECTIVE MEMORY COMPLAINERS: THE INSIGHT-PREAD STUDY

Cerebrospinal fluid (CSF) neurofilament light chain (NFL) protein has been shown to be a biomarker of large-caliber myelinated axonal disintegration, a pathophysiological mechanism associated with Alzheimer disease (AD). Since early detection of AD pathophysiology in blood samples is minimally invasive and potentially offers extensive and low-cost population screening, we assessed the association of plasma NFL concentrations with brain amyloid status in a preclinical cohort of cognitively normal subjects with subjective memory complaints. The INSIGHT-preAD study – a mono-centric French cohort established at the Pitié-Salpêtrière University Hospital in Paris with the goal to investigate the earliest preclinical stages of AD and its development – includes 318 cognitively normal Caucasian individuals, between 70–85 years old, with subjective memory complaints and with a defined brain amyloid status at baseline (T0). All subjects agreed to participate in a 5-year follow-up. Demographic, cognitive, functional, nutritional, biological, genetic, genomic, imaging, electrophysiological and other assessments were performed at T0. The mean age of the subjects was 76.1 (± 3.5) with a Mini-Mental State Examination (MMSE) score of 28.7 (± 0.95) and a predominance of females (62.9%). All subjects had a normal total recall at the Free and Cued Selective Reminding Test (FCRST) (mean 46.1 ± 2.0). When using a cutoff of 0.88, the amyloid-positive subgroup consisted of 64 subjects (27.7%). Plasma NFL concentrations were not significantly different in the amyloid-positive subgroup (31.26 ± 12.51 pg/mL) compared with the amyloid-negative subgroup (29.62 ± 12.89 pg/mL) (P=0.270). Plasma NFL concentrations did not significantly correlate with the mean cortical uptake of 18F-florbetapir. In this cross-sectional study, plasma NFL was not associated with brain amyloid status in individuals with subjective memory complaints. Data from ongoing longitudinal clinical follow-up will tell whether plasma NFL may predict future cognitive decline.