Early Stages Of Cognitive Decline Research Articles

Detection of Mild Cognitive Impairment Through Natural Language and Touchscreen Typing Processing.

Mild cognitive impairment (MCI), an identified prodromal stage of Alzheimer's Disease (AD), often evades detection in the early stages of the condition, when existing diagnostic methods are employed in the clinical setting. From an alternative perspective, smartphone interaction behavioral data, unobtrusively acquired in a non-clinical setting, can assist the screening and monitoring of MCI and its symptoms' progression. In this vein, the diagnostic ability of digital biomarkers, drawn from Fine Motor Impairment (FMI)- and Spontaneous Written Speech (SWS)-related data analysis, are examined here. In particular, keystroke dynamics derived from touchscreen typing activities, using Convolutional Neural Networks, along with linguistic features of SWS through Natural Language Processing (NLP), were used to distinguish amongst MCI patients and healthy controls (HC). Analytically, three indices of FMI (rigidity, bradykinesia and alternate finger tapping) and nine NLP features, related with lexical richness, grammatical, syntactical complexity, and word deficits, formed the feature space. The proposed approach was tested on two demographically matched groups of 11 MCI patients and 12 HC, having undergone the same neuropsychological tests, producing 4,930 typing sessions and 78 short texts, within 6 months, for analysis. A cascaded-classifier scheme was realized under three different feature combinations and validated via a Leave-One-Subject-Out cross-validation scheme. The acquired results have shown: (a) keystroke features with a k-NN classifier achieved an Area Under Curve (AUC) of 0.78 [95% confidence interval (CI):0.68–0.88; specificity/sensitivity (SP/SE): 0.64/0.92], (b) NLP features with a Logistic regression classifier achieved an AUC of 0.76 (95% CI: 0.65–0.85; SP/SE: 0.80/0.71), and (c) an ensemble model with the fusion of keystroke and NLP features resulted in AUC of 0.75 (95% CI:0.63–0.86; SP/SE 0.90/0.60). The current findings indicate the potentiality of new digital biomarkers to capture early stages of cognitive decline, providing a highly specific remote screening tool in-the-wild.

Cognition and motor function: The gait and cognition pooled index.

There is a need for outcome measures with improved responsiveness to changes in pre-dementia populations. Both cognitive and motor function play important roles in neurodegeneration; motor function decline is detectable at early stages of cognitive decline. This proof of principle study used a Pooled Index approach to evaluate improved responsiveness of the predominant outcome measure (ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale) when assessment of motor function is added. Candidate Pooled Index variables were selected based on theoretical importance and pairwise correlation coefficients. Kruskal-Wallis and Mann-Whitney U tests assessed baseline discrimination. Standardized response means assessed responsiveness to longitudinal change. Final selected variables for the Pooled Index include gait velocity, dual-task cost of gait velocity, and an ADAS-Cog-Proxy (statistical approximation of the ADAS-Cog using similar cognitive tests). The Pooled Index and ADAS-Cog-Proxy scores had similar ability to discriminate between pre-dementia syndromes. The Pooled Index demonstrated trends of similar or greater responsiveness to longitudinal decline than ADAS-Cog-Proxy scores. Adding motor function assessments to the ADAS-Cog may improve responsiveness in pre-dementia populations.

Using Automatic Assessment of Speech Production to Predict Current and Future Cognitive Function in Older Adults.

Neurodegenerative conditions like Alzheimer disease affect millions and have no known cure, making early detection important. In addition to memory impairments, dementia causes substantial changes in speech production, particularly lexical-semantic characteristics. Existing clinical tools for detecting change often require considerable expertise or time, and efficient methods for identifying persons at risk are needed. This study examined whether early stages of cognitive decline can be identified using an automated calculation of lexical-semantic features of participants’ spontaneous speech. Unimpaired or mildly impaired older adults (N = 39, mean 81 years old) produced several monologues (picture descriptions and expository descriptions) and completed a neuropsychological battery, including the Modified Mini-Mental State Exam. Most participants (N = 30) returned one year later for follow-up. Lexical-semantic features of participants’ speech (particularly lexical frequency) were significantly correlated with cognitive status at the same visit and also with cognitive status one year in the future. Thus, automated analysis of speech production is closely associated with current and future cognitive test performance and could provide a novel, scalable method for longitudinal tracking of cognitive health.

Arterial Stiffness and Cognition Among Adults: A Systematic Review and Meta‐Analysis of Observational and Longitudinal Studies

BackgroundTo estimate the strength of the cross‐sectional and longitudinal association between arterial stiffness, measured by pulse‐wave velocity, and cognitive function, distinguishing between global cognition, executive functions, and memory and to examine the influence of demographic, clinical, and assessment characteristics on this relationship.Methods and ResultsSystematic review of MEDLINE (via PubMed), Scopus, and WOS databases from their inception to March 2019, to identify cross‐sectional and longitudinal studies on the association between pulse‐wave velocity and cognitive domains (ie, global cognition, executive functions, and memory) among adult population. A total of 29 cross‐sectional and 9 longitudinal studies support the negative relationship between arterial stiffness and cognitive function, including global cognition, executive function, and memory. Demographic, clinical, and assessment characteristics did not substantially modify the strength of this association.ConclusionsEvidence reveals a negative association between arterial stiffness, measured using pulse‐wave velocity, and cognition, specifically executive function, memory, and global cognition. This association seems to be independent of demographic, clinical, and assessment characteristics. These results accumulate evidence supporting that pulse‐wave velocity assessment could be a useful tool to identify individuals at high risk of cognitive decline or early stages of cognitive decline, to implement interventions aimed at slowing the progression to dementia.

Semantic loss marks early Alzheimer's disease-related neurodegeneration in older adults without dementia.

ObjectiveTo assess progression of semantic loss in early stages of cognitive decline using semantic and letter fluency performance, and its relation with Alzheimer's disease (AD)‐specific neurodegeneration using longitudinal multimodal neuroimaging measures.MethodsChange in verbal fluency was analyzed among 2261 non‐demented individuals with a follow‐up diagnosis of no mild cognitive impairment (MCI), amnestic MCI (aMCI), non‐amnestic MCI (naMCI), or incident dementia, using linear mixed models across 4 years of follow‐up, and relations with magnetic resonance imaging (MRI; n = 1536) and 18F‐fluorodeoxyglucose brain positron emission tomography (18F‐FDG‐PET) imaging (n = 756) using linear regression models across 2 years of follow‐up.ResultsSemantic fluency declined—fastest in those at higher risk for AD (apolipoprotein E [APOE] e4 carriers, Clinical Dementia Rating score of .5, aMCI, or incident dementia)—while letter fluency did not except for those with incident dementia. Lower baseline semantic fluency was associated with an increase in white matter hyperintensities and total mean cortical thinning over time, and regionally with less hippocampal volume as well as more cortical thinning and reduced 18F‐FDG‐PET uptake in the inferior parietal lobule, entorhinal cortex, isthmus cingulate, and precuneus–posterior cingulate area. In contrast, baseline letter fluency was not associated with change in total nor regional neurodegeneration. Whole‐brain neurodegeneration over time was associated with faster decline in both fluencies, while AD‐specific regions were associated with a faster rate of decline in semantic but not letter fluency.InterpretationThis study provides strong evidence of distinctive degeneration of semantic abilities early on in relation to both cognitive decline and AD‐specific neurodegeneration.

The Effects of Standardized Ginkgo Biloba Extracts (GBE) on Subjective Cognitive Decline (SCD) in Middle-Aged Adults: A Review

Subjective cognitive decline (SCD) is defined as the presence of self-reported cognitive complaints with unimpaired performance in neuropsychological cognitive tests. SCD has been identified as a precursor of mild cognitive impairment (MCI) and potentially represents the earliest clinical sign of Alzheimer’s disease (AD). Standardized extracts of Ginkgo biloba (GBE) are widely used as a treatment for cognitive impairment. Nonetheless, most of the available review articles focus on the effects of GBE in MCI and dementia but not in SCD and its specific cognitive effects. Thus, this review collects and discusses the available published clinical data for the effects of standardized GBE on the early stages of cognitive decline among an age group where SCD becomes a topic—the middle-aged adults. Randomized clinical trials (RCTs), systematic reviews and meta-analyses of standardized GBEs in cognitive decline subjects were searched using PubMed/MEDLINE, Science direct, Cochrane, and Google Scholar until January 2019. Data from relevant RCT were critically evaluated to determine the potential effects of GBE on SCD. The results showed that the number of available GBE studies on SCD is small. Eight studies were selected in which subjects reported memory impairment, in some cases with concerns (worries), and with an average age at onset SCD of 60 years. Six studies gave a proof of efficacy for GBE for the treatment of SCD in at least one cognitive parameter. One study is inconclusive, however, a post-hoc analysis demonstrates efficacy in preventing AD with intake >4 years. The most common GBE dosage used was 240 mg GBE/day over a minimum period of 8 weeks. Hence, there might be beneficial effects of GBE to prevent, improve or delay SCD in the generation of 50 years or older. However, larger, well-defined RCTs using SCD criteria are necessary to further substantiate this effect in SCD subjects.

Participant and Study Partner Reported Impact of Cognition on Functional Activities in Parkinson's Disease.

Cognitive dysfunction is common in Parkinson's disease (PD) and associated with reduced functional abilities and increased dependence. To date, however, little is known about the relationship between performance of instrumental activities of daily living (IADLs) and cognitive stages in PD, and there are conflicting reports as to whether declines in specific cognitive domains predict IADL impairment. Participants with PD were drawn from the Pacific Udall Center and included in the study if both participant and study partner IADL ratings and cognitive tests were completed (n = 192). Logistic regression analyses were performed to determine whether participant and/or study partner rating predicted mild cognitive impairment or dementia. Correlations are reported for the relationship between participant/study partner IADL reports as well as for specific cognitive tests. Although both participant and study partner ratings of IADL performance were associated with a diagnosis of PD with dementia, only participant self-rating of functional ability was significantly associated with a diagnosis of PD with mild cognitive impairment. Functional ability correlated most strongly with measures of processing speed, auditory working memory, and immediate verbal recall for both the participant and study partner ratings. For participants with PD in the early stages of cognitive decline, self-rating may be more sensitive to the impact of cognitive changes on IADL function than ratings made by a knowledgeable study partner. Changes in executive function, processing speed, and learning may indicate a higher likelihood of IADL impairment. Careful assessment of cognition and IADL performance is recommended to permit individualized interventions prior to significant disability.

The relationship between the gut microbiome and mild cognitive impairment in patients without dementia: a cross-sectional study conducted in Japan

Recent studies have revealed an association between the dysregulation of the gut microbiome and dementia. However, whether this dysregulation is associated with mild cognitive impairment (MCI), an early stage of cognitive decline, in patients without dementia remains unclear. We performed a cross-sectional analysis to determine the association between the gut microbiome and MCI. Data, including patient demographics, risk factors, cognitive function, and brain imaging, were collected. The gut microbiome was assessed through terminal restriction fragment length polymorphism analysis. Multivariable logistic regression models were used to identify factors independently associated with MCI. Graphical modelling was used to illustrate mutual associations between MCI and identified factors. We analysed 82 patients, 61 of whom exhibited MCI. Patients with MCI had a higher prevalence of Bacteroides. Furthermore, patients with more Bacteroides were more likely to present with white matter hyperintensity and high voxel-based specific regional analysis system for Alzheimer’s Disease (VSRAD) scores, indicating cortical and hippocampal atrophy. A multivariable logistic regression analysis revealed that a greater prevalence of Bacteroides was independently associated with MCI. Graphical modelling also showed a close association between Bacteroides and MCI. In conclusion, an increased prevalence of Bacteroides is independently associated with the presence of MCI in patients without dementia.

Suppressing aberrant phospholipase D1 signaling in 3xTg Alzheimer\u2019s disease mouse model promotes synaptic resilience

Current approaches in treatment of Alzheimer’s disease (AD) is focused on early stages of cognitive decline. Identifying therapeutic targets that promote synaptic resilience during early stages may prevent progressive memory deficits by preserving memory mechanisms. We recently reported that the inducible isoform of phospholipase D (PLD1) was significantly increased in synaptosomes from post-mortem AD brains compared to age-matched controls. Using mouse models, we reported that the aberrantly elevated neuronal PLD1 is key for oligomeric amyloid driven synaptic dysfunction and underlying memory deficits. Here, we demonstrate that chronic inhibition using a well-tolerated PLD1 specific small molecule inhibitor is sufficient to prevent the progression of synaptic dysfunction during early stages in the 3xTg-AD mouse model. Firstly, we report prevention of cognitive decline in the inhibitor-treated group using novel object recognition (NOR) and fear conditioning (FC). Secondly, we provide electrophysiological assessment of better synaptic function in the inhibitor-treated group. Lastly, using Golgi staining, we report that preservation of dendritic spine integrity as one of the mechanisms underlying the action of the small molecule inhibitor. Collectively, these studies provide evidence for inhibition of PLD1 as a potential therapeutic strategy in preventing progression of cognitive decline associated with AD and related dementia.

The relationship between the gut microbiome and mild cognitive impairment in patients without dementia: A cross-sectional study conducted in Japan

Recent studies have revealed an association between the dysregulation of the gut microbiome and dementia. However, whether this dysregulation is associated with mild cognitive impairment (MCI), an early stage of cognitive decline, in patients without dementia remains unclear. We performed a cross-sectional analysis to determine the association between the gut microbiome and MCI. Data, including patient demographics, risk factors, cognitive function, and brain imaging, were collected. The gut microbiome was assessed through terminal restriction fragment length polymorphism analysis. Multivariable logistic regression models were used to identify factors independently associated with MCI. Graphical modelling was used to illustrate mutual associations between MCI and identified factors. We analysed 82 patients, 61 of whom exhibited MCI. Patients with MCI had a higher prevalence of Bacteroides. Furthermore, patients with more Bacteroides were more likely to present with white matter hyperintensity and high voxel-based specific regional analysis system for Alzheimer’s Disease (VSRAD) scores, indicating cortical and hippocampal atrophy. A multivariable logistic regression analysis revealed that a greater prevalence of Bacteroides was independently associated with MCI. Graphical modelling also showed a close association between Bacteroides and MCI. In conclusion, an increased prevalence of Bacteroides is independently associated with the presence of MCI in patients without dementia.

Effect of poor sleep quality on subjective cognitive decline (SCD) or SCD-related functional difficulties: Results from 220,000 nationwide general populations without dementia

ObjectiveThis study aimed to elucidate the relationships among sleep quality, subjective cognitive decline (SCD), and SCD-related functional limitation. MethodsThe present study used the 2018 Korea Community Health Survey (KCHS) data, which comprise community-based, nationwide representative data collected by the Korea Centers for Disease Control and Prevention. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). The study population comprised 203,082 persons aged ≥ 19 years. ResultsAmong 203,082 subjects, 35,892 (17.7%) had SCD and 4,373 (2.2%) had SCD-related functional limitation. Individuals with poor sleep quality (PSQI > 5) were approximately 2-fold more likely to exhibit SCD and SCD-related functional limitation (SCD: Odds ratio [OR] = 1.983, 95% confidence interval [CI] = 1.915–2.054; SCD-related functional limitation: OR = 2.405, 95% CI = 2.158–2.681). Moreover, younger adults showed a greater influence of sleep quality on SCD and SCD-related functional limitation, compared to older adults. LimitationsBecause this study used cross-sectional data, it could not establish a causal relationship among poor sleep quality, SCD, and SCD-related functional limitation. ConclusionsPoor sleep quality might contribute to cognitive and functional decline. The present study showed that, in both younger and older adults, there is a need to identify early stages of cognitive decline (e.g., SCD), as well as to perform intervention to prevent poor sleep quality and cognitive decline.

Inflammation in mild cognitive impairment due to Parkinson's disease, Lewy body disease, and Alzheimer's disease.

Inflammation appears to play a role in the progression of neurodegenerative diseases. However, little is known about inflammation during early stages of cognitive decline or whether this differs in different disease groups. We sought to investigate this by assessing the inflammatory profile in patients with Parkinson disease with the early stages of cognitive impairment (PD-MCI), patients with prodromal Alzheimer disease (MCI-AD), prodromal Lewy body disease (MCI-LB), and controls. We obtained venous blood samples from participants with PD-MCI (n=44), PD-normal cognition (n=112), MCI-LB (n=38), MCI-AD (n=21), and controls (n=84). We measured 10 cytokines using Meso Scale Discovery V-Plex Plus including interferon gamma, interleukin (IL)-10, IL-12p70, IL-13, IL-1beta, IL-2, IL-4, IL-6, IL-8, and tumour necrosis factor alpha. High-sensitivity C-reactive protein was measured. There was a higher level of inflammation in patients with MCI-AD and MCI-LB compared with controls. PD noncognitively impaired had higher inflammatory markers than controls, but there was no difference between PD-MCI and controls. There was a decrease in inflammatory markers with increasing motor severity based on the Unified Parkinson's Disease Rating Scale. Inflammation may be involved in the onset of cognitive decline in patients with MCI-AD and MCI-LB but appears to be less prominent PD-MCI albeit in a small data set. This suggests that anti-inflammatory medications may have most benefit at the earliest stages of neurodegenerative diseases. For PD cases, this might be in advance of the development of MCI.

Protocol for a systematic review on interventions for caregivers of persons with mild cognitive impairment and early dementia: does early stage intervention improve caregiver well-being and ability to provide care?

IntroductionCaregivers of persons with dementia and mild cognitive impairment (MCI) are at risk of decreased well-being. While many interventions for caregivers exist, evidence is sparse regarding intervention timing and effectiveness...

Cognitive Impact of Cerebral Small Vessel Disease Changes in Patients With Hypertension.

Hypertension is one of the principal risk factors for cerebral small vessel disease progression and cognitive impairment. We aimed to investigate how changes in cerebral small vessel disease lesions relate to cognitive decline and incident mild cognitive impairment in hypertensive patients. Data were obtained from the ISSYS cohort (Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study)-a longitudinal population-based study on hypertensive patients aged 50 to 70 years without dementia and stroke at baseline. Patients underwent a brain magnetic resonance imaging, a cognitive screening test, and cognitive diagnosis (normal aging or mild cognitive impairment) at baseline and follow-up. We evaluated incident lacunar infarcts and cerebral microbleeds. Changes in the periventricular and deep white matter hyperintensities (WMH) were qualitatively defined as none, minor, or marked. We followed up 345 patients (median age, 65 [61-68]; 55.4% men) for 3.95 (3.83-4.34) years. Incident mild cognitive impairment was diagnosed in 9.1% of the sample. Considering the progression of cerebral small vessel disease, the prevalence of incident infarcts was 6.1% and that of incident cerebral microbleeds was 5.5%; progression of periventricular WMH was 22% and that of deep WMH was 48%. Patients with marked progression of periventricular WMH showed a significant decrease in global cognition compared with patients without progression (adjusted mean [SE], -0.519 [0.176] versus 0.057 [0.044], respectively; P value=0.004) and a higher risk of incident mild cognitive impairment (OR, 6.184; 95% CI, 1.506-25.370; P value=0.011). Therefore, our results indicate that hypertensive patients with progression of periventricular WMH have higher odds of cognitive impairment, even in the early stages of cognitive decline.

Effect of interactive cognitive-motor training on eye-hand coordination and cognitive function in older adults

BackgroundPoor eye–hand coordination is associated with the symptoms of the early stage of cognitive decline. However, previous research on the eye–hand coordination of older adults without cognitive impairment is scant. Therefore, this study examined the effects of interactive cognitive-motor training on the visual-motor integration, visual perception, and motor coordination sub-abilities of the eye–hand coordination and cognitive function in older adults.MethodsA double-blind randomized controlled trial was conducted with older adults. Sixty-two older adults were randomly assigned to the experimental (interactive cognitive-motor training) or active control (passive information activity) group, and both groups received 30 min of training each week, three times a week for 8 weeks. The primary outcome was eye–hand coordination, which was further divided into the sub-abilities of visual–motor integration, visual perception, and motor coordination. The secondary outcome was cognitive function. The generalized estimating equation was used to examine differences in immediate posttest, 3-month posttest, and 6-month posttest results between the two groups. Additionally, the baseline effect sizes were compared with the effect sizes of the immediate posttest, 3-month posttest, and 6-month posttests for the experimental group.ResultsThere were no statistically significant differences between the intervention and control groups. The only statistically significant difference between the groups was in the attention dimension of cognitive function (p = 0.04). The visual–motor integration results showed a small to moderate effect size for pre post comparisons.ConclusionsThe 24 sessions of interactive cognitive-motor training showed no difference to an active control intervention. In the future, this intervention could be further investigated to establish whether it can be superior to an active control group in other populations.Trial registrationThe study protocol has been published on Chinese Clinical Trial Registry (ChiCTR) (registry no.: ChiCTR-IOR-14005490).

Free-water imaging of the hippocampus is a sensitive marker of Alzheimer's disease.

Validating sensitive markers of hippocampal degeneration is fundamental for understanding neurodegenerative conditions such as Alzheimer's disease. In this paper, we test the hypothesis that free-water in the hippocampus will be more sensitive to early stages of cognitive decline than hippocampal volume, and that free-water in hippocampus will increase across distinct clinical stages of Alzheimer's disease. We examined two separate cohorts (N = 126; N = 112) of cognitively normal controls, early and late mild cognitive impairment (MCI), and Alzheimer's disease. Demographic, clinical, diffusion-weighted and T1-weighted imaging, and positron emission tomography (PET) imaging were assessed. Results indicated elevated hippocampal free-water in early MCI individuals compared to controls across both cohorts. In contrast, there was no difference in volume of these regions between controls and early MCI. ADNI free-water values in the hippocampus was associated with low CSF AB1–42 levels and high global amyloid PET values. Free-water imaging of the hippocampus can serve as an early stage marker for AD and provides a complementary measure of AD neurodegeneration using non-invasive imaging.

The Assessment of Cerebrovascular Response to a Language Task from the Addenbrooke's Cognitive Examination in Cognitive Impairment: A Feasibility Functional Transcranial Doppler Ultrasonography Study.

Background:The incidence of dementia is predicted to rise rapidly, but sensitive diagnostic tests remain elusive. Changes in cerebral blood flow velocity (CBFv) can occur at an early stage of cognitive decline, and can be measured by transcranial Doppler ultrasonography (TCD).Objective: The aim of this study was to characterize the CBFv changes that occur in healthy older adults (HC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD), in response to a language task from the Addenbrooke’s cognitive examination (ACE-III).Methods:Participants underwent bilateral TCD, continuous heart rate (ECG), end-tidal CO2 (capnography, ETCO2), and beat-to-beat blood pressure (Finometer, MAP), monitoring, during a 5-minute baseline, followed by cognitive tasks from the ACE-III. Data are presented for a language task (repeating words and phrases aloud), as peak percentage change in CBFv, HR, MAP, and ETCO2 from a normalized baseline.Results: 30 participants (mean age 73.2 years, 20% female) were recruited; HC (n = 10), MCI (n = 10), AD (n = 10). Language scores did not differ between groups (p = 0.16). Peak percentage change in CBFv differed between groups with the language task (HC: 15.9 (7.5)%, MCI: 6.7 (4.5)%, AD: 0.1 (7.1)%; p < 0.005). However, changes in MAP (HC: 7.9 (4.6)%, MCI: –0.1 (0.9)%, AD: 0.9 (4.4)%; p < 0.005), HR (HC: 8.8 (8.2)%, MCI: 0.7 (4.3)%, AD: –0.5 (5.6)%; p = 0.005), and ETCO2 (HC: –0.9 (3.2)%, MCI: 0.9 (3.2)%, AD: –5.2 (5.7)%; p = 0.006), also occurred.Conclusions: TCD measured CBFv changes to a language task from the ACE-III was feasible in a cognitively impaired population, further work is required in a larger population.

Multilingual word embeddings for the assessment of narrative speech in mild cognitive impairment

We analyze the information content of narrative speech samples from individuals with mild cognitive impairment (MCI), in both English and Swedish, using a combination of supervised and unsupervised learning techniques. We extract information units using topic models trained on word embeddings in monolingual and multilingual spaces, and find that the multilingual approach leads to significantly better classification accuracies than training on the target language alone. In many cases, we find that augmenting the topic model training corpus with additional clinical data from a different language is more effective than training on additional monolingual data from healthy controls. Ultimately we are able to distinguish MCI speakers from healthy older adults with accuracies of up to 63% (English) and 72% (Swedish) on the basis of information content alone. We also compare our method against previous results measuring information content in Alzheimer’s disease, and report an improvement over other topic-modeling approaches. Furthermore, our results support the hypothesis that subtle differences in language can be detected in narrative speech, even at the very early stages of cognitive decline, when scores on screening tools such as the Mini-Mental State Exam are still in the “normal” range.

Initial cognitive changes in Parkinson's disease.

The focus on cognitive impairment in neurodegenerative diseases, including PD, is shifting from the dementia stage to earlier stages of impairment, including mild cognitive impairment. This shift is driven primarily by the desire to improve long-term outcomes by delivering therapeutic interventions earlier in the clinical course, even presymptomatically in those at highest risk, and at the initial stage in the pathophysiological cascade that underpins common dementia syndromes. This article focuses on key findings and challenges in studying earliest stages of cognitive decline in PD, including a detailed examination of neuropsychological testing, cognitive performance in early and prodromal PD, epidemiological research for PD mild cognitive impairment to date, and expert recommendations for assessment. © 2018 International Parkinson and Movement Disorder Society.

Can you detect early dementia from an email? A proof of principle study of daily computer use to detect cognitive and functional decline.

ObjectiveTo determine whether multiple computer use behaviours can distinguish between cognitively healthy older adults and those in the early stages of cognitive decline, and to investigate whether these behaviours are associated with cognitive and functional ability.MethodsOlder adults with cognitive impairment (n = 20) and healthy controls (n = 24) completed assessments of cognitive and functional abilities and a series of semi‐directed computer tasks. Computer use behaviours were captured passively using bespoke software.ResultsThe profile of computer use behaviours was significantly different in cognitively impaired compared with cognitively healthy control participants including more frequent pauses, slower typing, and a higher proportion of mouse clicks. These behaviours were significantly associated with performance on cognitive and functional assessments, in particular, those related to memory.ConclusionUnobtrusively capturing computer use behaviours offers the potential for early detection of neurodegeneration in non‐clinical settings, which could enable timely interventions to ultimately improve long‐term outcomes.