The cingulate island sign in a mixed memory clinical cohort: Prevalence and diagnostic accuracy.

INTRODUCTION: Visual rating of the cingulate island sign (CIS) on [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) has a high specificity for dementia with Lewy bodies (DLB) in selected cohorts such as DLB versus Alzheimer's disease (AD). In a mixed memory clinical population this study aimed to uncover the prevalence of CIS, the diagnostic accuracy for DLB, and the relationship between CIS and disease severity. METHODS: CIS on [18F]FDG-PET was retrospectively assessed with the visual CIS rating scale (CISRs) in 1000 patients with a syndrome diagnosis of mild cognitive impairment (MCI) or dementia with no restrictions in etiological diagnosis. RESULTS: In this cohort 24.3 % had a CISRs score ≥1 and 3.5 % had a CISRs score = 4. The prevalence of a CISRs score ≥1 was highest in DLB (74.0 %, n = 57). A CISRs score ≥1 was present in at least 9 % in other diagnostic groups. The prevalence of CIS across disease severities showed no statistically significant difference (p = 0.23). To differentiate DLB from non-DLB the optimal cut-off was a CISRs score ≥1 (balanced accuracy = 77.1 %) in MCI/mild dementia and a CISRs score ≥2 (balanced accuracy = 80.6 %) in moderate/severe dementia. The positive predictive value of a CISRs score = 4 for DLB was 57.7 % in MCI/mild dementia and 33.3 % in moderate/severe dementia. CONCLUSION: The CISRs is useful in differentiating DLB from other etiologies in a mixed memory clinical population. Balanced accuracy and positive predictive value may vary across disease severities in the population studied.

Different language profiles on neuropsychological tests in dementia with Lewy bodies and Alzheimer's disease.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) may lead to different cognitive profiles. The performance on single language tests have been investigated in these patient-groups, but few studies have compared DLB and AD patients' language performances on different types of tests. The aim was to compare performances for patients with DLB, AD and healthy controls on different aspects of language function. Boston Naming Test, Naming of famous faces and verbal fluency (both semantic and lexical) were investigated in 90 DLB patients, 77 matched AD patients (MMSE score ≥ 21), and in a control group (N = 61). The patients had significantly lower scores on all tests compared to controls. The AD patients scored significantly lower than DLB patients on naming measures whereas the lexical fluency score was significantly lower in DLB. No significant differences were found for the semantic fluency. The frequency of impairment on the Boston Naming Test was higher in AD as compared to DLB, whereas the frequency of impairment on the lexical fluency test was significantly higher in DLB. In conclusion, DLB may lead to a different language profile than AD, and performance on language-based tests may help to differentiate patients with AD and DLB.

Psychological test usage in duchenne muscular dystrophy: An EU multi-centre study.

AIM: During the last two decades brain related comorbidities of Duchenne have received growing scientific and clinical interest and therefore systematic assessment of cognition, behaviour and learning is important. This study aims to describe the instruments currently being used in five neuromuscular clinics in Europe as well as the diagnoses being made in these clinics. METHOD: A Delphi based procedure was developed by which a questionnaire was sent to the psychologist in five of the seven participating clinics of the Brain Involvement In Dystrophinopathy (BIND) study. Instruments and diagnoses being used were inventoried for three domains of functioning (cognition, behaviour and academics) and three age groups (3-5 years, 6-18 years and adulthood 18+ years). RESULTS: Data show wide diversity of tests being used in the five centres at different age groups and different domains. For the intelligence testing there is consensus in using the Wechsler scales, but all other domains such as memory, attention, behavioural problems and reading are tested in very different ways by different instruments in the participating centres. CONCLUSION: The heterogeneity of tests and diagnoses being used in current clinical practice underlines the importance for developing a Standard Operating Procedure (SOP) to improve both clinical practice and scientific research over different countries and improve comparative work.

Clinical validation of the cingulate island sign visual rating scale in dementia with Lewy bodies.

INTRODUCTION: The cingulate island sign (CIS) is a metabolic pattern on [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) associated with dementia with Lewy bodies (DLB). The aim of this study was to validate the visual CIS rating scale (CISRs) for the diagnosis of DLB and to explore the clinical correlates. METHODS: This single-center study included 166 DLB patients and 161 patients with Alzheimer's disease (AD). The CIS on [18F]FDG-PET scans was rated using the CISRs independently by three blinded raters. RESULTS: The optimal cut-off to differentiate DLB from AD was a CISRs score ≥ 1 (sensitivity = 66%, specificity = 84%) whereas a CISRs score ≥ 2 (sensitivity = 58%, specificity = 92%) was optimal to differentiate amyloid positive DLB (n = 43 (82.7%)) and AD. To identify DLB with abnormal (n = 53 (72.6%)) versus normal (n = 20 (27.4%)) dopamine transporter imaging, a CISRs cut-off of 4 had a specificity of 95%. DLB with a CISRs score of 4 performed significantly better in tests on free verbal recall and picture based cued recall, but worse on processing speed compared to DLB with a CISRs score of 0. CONCLUSION: This study confirms the CISRs as a valid marker for the diagnosis of DLB with a high specificity and a lower, but acceptable, sensitivity. Concomitant AD pathology does not influence diagnostic accuracy of the CISRs. In DLB patients, presence of CIS is associated with relative preserved memory function and impaired processing speed.

Subjective Complaints are Similar in Subjective Cognitive Decline and Early-Stage Alzheimer's Disease when Assessed in a Memory Clinic Setting.

BACKGROUND: Subjective cognitive complaints are generally poorly associated with objective memory functioning in older persons. Subjective cognitive decline (SCD) is a key feature in SCD and amnestic mild cognitive impairment (aMCI) which both can represent early Alzheimer's disease (AD). The aim of this study was to assess how memory clinic patients with SCD, MCI and mild AD dementia scored on 3 different complaint measures and if the format of assessment had an impact on the association with cognitive functioning, age, and depressive symptoms. METHODS: We included 17 SCD patients, 17 aMCI patients, 17 patients with mild AD, and 30 controls. Complaints were assessed with the Cognitive Change Index (CCI), the Subjective Memory Complaints (SMC) scale, and the Memory Complaint Questionnaire (MAC-Q). RESULTS: There were no significant differences between the total scores in the patient groups on the questionnaires. However, significant differences were found in the number of patients classified with impairment when using the CCI, the SMC, and the MAC-Q. Scores on all questionnaires were significantly associated with depressive symptoms, and significant associations with age, gender, and Addenbrookes Cognitive Examination score were found for the SMC. In patients with cognitive dysfunction, lower memory awareness significantly predicted fewer cognitive complaints. CONCLUSIONS: SCD patients in a memory clinic setting report the same degree of cognitive impairment as patients with aMCI and mild dementia, and in a hospital-based cohort we extend previous findings from healthy controls, that definition of SCD may depend on the format of assessment.

Characterising the prodromal phase in dementia with Lewy bodies.

INTRODUCTION: Three presentations of prodromal dementia with Lewy bodies (DLB) have recently been proposed. This study investigates the frequency of symptoms in the prodromal phase of DLB. METHOD: Patients diagnosed with DLB between the 1st of February 2017 and 1st of February 2021 were retrospectively identified and matched to a group of patients diagnosed with Alzheimer's disease (AD). Patient case files were reviewed identifying the first symptoms and symptoms in the prodromal phase (cognitive impairment, psychiatric symptoms, delirium/acute confusional episodes, RBD, motor symptoms indicative of Parkinson's disease, anosmia, and autonomic dysfunction). RESULTS: A total of 166 DLB patient and 168 AD patients were included. Of the proposed presentations in patients diagnosed with DLB, 30% presented with cognitive impairment at onset in isolation, 6% with psychiatric symptoms, and 2% with delirium/acute confusional episodes. Prodromal DLB was more likely to present with no cognitive symptoms at initial presentation (38% vs 10%) and was more likely to involve other symptoms (69% vs 26%). Of other possible presentations, Rapid eye-movement sleep Behaviour Disorder (RBD) was found at onset in 22% with a mean prodromal length of 8.4 years (all symptoms: mean 4.3 years, SD 5.8). CONCLUSION: We found some supportive evidence of the proposed cognitive and psychiatric presentations of prodromal DLB. Our findings build on previous findings that an RBD presentation exist, and further research is needed to characterise this presentation.

On the association between apathy and deficits of social cognition and executive functions in Huntington's disease.

OBJECTIVE: To investigate if executive and social cognitive dysfunction was associated with apathy in a large cohort of Huntington's disease gene expansion carriers. METHOD: Eighty premanifest and motor-manifest Huntington's disease gene expansion carriers (Mini-Mental State Examination score ≥ 24 and Montreal Cognitive Assessment score ≥ 19) and thirty-two controls were examined with the Lille Apathy Rating Scale (LARS), a tailored and quantitative measure of apathy, and a comprehensive cognitive battery on executive functions and social cognition (emotion recognition, theory of mind and sarcasm detection), as well as general correlates like demographic variables, and neuropsychiatric and cognitive screening tests. RESULTS: The motor-manifest Huntington's disease gene expansion carriers had significantly different scores on most measures of social cognition and executive functions, compared to premanifest and control participants. Apathy was significantly correlated with most executive test scores, but the Emotion Hexagon was the only social cognitive test score significantly correlated with apathy. We found that the motor score and the depression score were the only significant predictors of the apathy score, when the social cognitive and executive tests with the strongest association with the global LARS score were entered into a multiple stepwise regression model. No cognitive test score could significantly predict apathy. The model explained 21 % of the total variance. CONCLUSION: Despite being significantly correlated with apathy neuropsychological variables did not have a significant impact on apathy when variables as depression and motor symptoms were taken into account. Apathy should be considered an independent symptom of Huntington's disease that requires specific examination.

[Christmas article: Copenhagen Christmas Cognitive Examination].

Introduction Motivation is important when administering cognitive tests. Routine cognitive testing may become trivial both for the examiner and the test subject when using tests that only incorporate neutral items. We hypothesized that a Christmas themed cognitive test could improve motivation for cognitive testing and might elicit positive emotional reactions. Methods We devised the Copenhagen Christmas Cognitive Examination (CCCE), a quickly administered test with ten items, all with Christmas themed content. The CCCE evaluates various important areas of cognition including anterograde and retrograde memory, visuoconstruction, naming and executive function. In this cross-sectional pilot study, we tested feasibility and further explored the possible emotional and motivational effects by administering a questionnaire with a 5-point Likert scale indicating agreement with statements regarding mood and motivation after testing. Results A total of 14 cognitively healthy participants (mean age 42 years (SD 12.3)) underwent testing with the CCCE. A high level of positive mood and motivation was present for most subjects after testing. Being in a Christmas mood after testing was significantly associated with higher test scores (Spearman's correlation coefficient 0.53, p = 0.019). Conclusion It was feasible to administer a Christmas themed cognitive test, and test subjects experienced positive emotional reactions after testing. Further testing in a non-healthy population is warranted. Funding none. Trial registration none.

Developing a Danish version of the LASSI-L test - reliability and predictive value in patients with mild cognitive impairment, mild dementia due to AD and subjective cognitive decline.

Tests measuring proactive semantic interference as The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), has shown promising diagnostic properties for the diagnosis of Mild Cognitive Impairment (MCI) and dementia. LASSI-L may also be efficient in predicting cognitive decline in at-risk individuals. There is an unmet need to examine the diagnostic properties of the LASSI-L in a Danish context where traditional neuropsychological tests are typically applied when diagnosing possible dementia disorders. To investigate the reliability, convergent validity, and predictive value of the new Danish LASSI-L version in aMCI and mild dementia due to Alzheimer's disease (AD). From a memory clinic we included 17 aMCI patients, 15 patients with mild dementia (AD), 17 patients with Subjective Cognitive Decline (SCD), and 30 healthy controls. Neuropsychological assessment was applied in all patients, and biomarker analyses were performed for patients with aMCI and mild AD. Cronbach's alpha was 0.94. Patients with aMCI and mild dementia differed significantly from healthy controls on all LASSI-L measures. ROC analyses showed a very high AUC value for both patients with aMCI [0.85-0.97] and mild dementia [0.93-0.99]. SCD patients generally did not differ from controls, except for significantly lower scores on one item (Cued Recall A1) LASSI-L had high reliability and promising predictive value in the diagnosis of aMCI and mild AD due to AD. SCD patients diagnosed in a memory clinic did not differ significantly from healthy on the LASSI-L.

Clinical Markers of 6 Pre-dominant Coping Behaviors in Living With Parkinson Disease: A Convergent Mixed Methods Study.

People with Parkinson's disease (PwP) experience a variety of symptoms and fluctuations in these, which they have to cope with every day. In tailoring a person-centered treatment to PwP there is a lack of knowledge about the association between pre-dominant coping behaviors and clinical markers among PwP. To describe and compare specific clinical markers between 6 suggested coping behaviors. Thirty-four PwP, who previously had been classified into 6 different pre-dominant coping behaviors, were included in this mixed methods study. Six primary variables were included in the descriptive analysis; motor function (UPDRS-III), non-motor symptoms score (NMS-Quest), change in bradykinesia score, apathy score (LARS), personality traits (NEO-FFI), and cognitive status (evaluated by a neuropsychologist). The merged results of this mixed methods study indicate that clinical markers as apathy, burden of non-motor symptoms, cognitive impairments and personality traits, have the potential to impact the coping behavior in PwP. In a clinical setting the markers; NMS-burden, degree of apathy, cognition, and personality traits may indicate specific coping behavior. Three of the six suggested typologies of coping behaviors differed from the other groups when comparing descriptive data. In order to improve patient care and guide the development of person-centered therapies, each PwP should be approached based on those typologies.

An Exploratory Study Investigating Autonomy in Huntington's Disease Gene Expansion Carriers.

BACKGROUND: Autonomy describes a psychological state of self-regulation of motivation and action, which is a central characteristic of healthy functioning. In neurodegenerative diseases measures of self-perception have been found to be affected by the disease. However, it has never been investigated whether measures of self-perception, like autonomy, is affected in Huntington's disease. OBJECTIVE: We investigated whether autonomy is affected in Huntington's disease and if the degree of autonomy is associated with motor function, neuropsychiatric symptoms, cognitive impairments, and apathy. METHODS: We included 44 premanifest and motor-manifest Huntington's disease gene expansion carriers and 19 controls. Autonomy was examined using two self-report questionnaires, the Autonomy-Connectedness Scale-30 and the Index of Autonomous Functioning. All participants were examined according to motor function, cognitive impairments, and neuropsychiatric symptoms, including apathy. RESULTS: Statistically significant differences were found between motor-manifest Huntington's disease gene expansion carriers and premanifest Huntington's disease gene expansion carriers or controls on two measures of autonomy. Between 25-38% of motor-manifest Huntington's disease gene expansion carriers scored significantly below the normal level on subscales of autonomy as compared to controls. One autonomy subscale was associated with apathy (r = -0.65), but not with other symptoms of Huntington's disease. CONCLUSION: This study provides evidence for impaired autonomy in individuals with Huntington's disease and an association between autonomy and apathy. The results underline the importance of maintaining patient autonomy and involvement in care throughout the disease.

Decreased CSF oxytocin relates to measures of social cognitive impairment in Huntington's disease patients.

OBJECTIVE: Huntington's disease (HD) is an inherited neurodegenerative disease with motor, cognitive and psychiatric symptoms. Non-motor symptoms like depression and altered social cognition are proposed to be caused by dysfunction of the hypothalamus. We measured the hypothalamic neuropeptide oxytocin in plasma and cerebrospinal fluid (CSF) in a cohort of HD gene expansion carriers (HDGECs), compared the levels to healthy HD family controls and correlated oxytocin levels to disease progression and social cognition. METHODS: We recruited 113 HDGECs and 33 controls. Psychiatric and cognitive symptoms were evaluated, and social cognition was assessed with the Emotion Hexagon test, Reading the Mind in the Eyes and The Awareness of Social Inference Test. The levels of oxytocin in CSF and blood were analyzed by radioimmunoassay. RESULTS: We found the level of oxytocin in CSF to be significantly lower by 33.5% in HDGECs compared to controls (p = 0.016). When dividing the HDGECs into groups with or without cognitive impairment, we found the oxytocin level to be significantly lower by 30.3% in the HDGECs with cognitive symptoms (p = 0.046). We found a statistically significant correlation between the level of oxytocin and scores on social cognition (Reading the Mind in the Eyes p = 0.0019; Emotion Hexagon test: p = 0.0062; The Awareness of Social Inference Test: p = 0.002). CONCLUSIONS: This is the first study to measure oxytocin in the CSF of HDGECs. We find that HDGECs have a significantly lower level of oxytocin compared to controls, and that the level of oxytocin may represent an objective and comparable measure that could be used as a state biomarker for impairment of social cognition. We suggest treatment trials to evaluate a potential effect of oxytocin on social cognition in HD.

Impairments of social cognition significantly predict the progression of functional decline in Huntington's disease: A 6-year follow-up study.

This study sought to investigate if there was a significant difference between the Huntington's Disease gene expansion carriers who were impaired on the cognitive domains, social cognition and executive functions. Also, it was investigated which of the cognitive domains could predict the decrease in total functional capacity over a 6-year follow-up period. Premanifest and motor-manifest Huntington's Disease gene expansion carriers (N = 98), were examined with a neurological and neuropsychological examination at Time 1 (year 2012-2013). Regression-based normative data was used to classify impairments on the two cognitive domains. Follow-up participants (N = 80) had their functional capacity reexamined at Time 2 (year 2018-2020), to examine which cognitive domain could predict the decrease in functional capacity over the 6-year follow-up. More than 50% of the participants were impaired on the domain of social cognition. These participants were significantly different from the participants who were impaired on executive functions. The motor function and impairments on social cognition significantly predicted the decline in functional capacity. The Emotion Hexagon test was the only significant social cognitive task, that predicted the decline in functional capacity. Social cognition includes unique and separate functions in Huntington's Disease, unaffected by executive functions. This study emphasizes the importance of regular assessment of social cognition in Huntington's Disease and the clinical relevance of impaired social cognitive function.

Listen Carefully protocol: an exploratory case-control study of the association between listening effort and cognitive function.

INTRODUCTION: A growing body of evidence suggests that hearing loss is a significant and potentially modifiable risk factor for cognitive impairment. Although the mechanisms underlying the associations between cognitive decline and hearing loss are unclear, listening effort has been posited as one of the mechanisms involved with cognitive decline in older age. To date, there has been a lack of research investigating this association, particularly among adults with mild cognitive impairment (MCI). METHODS AND ANALYSIS: 15-25 cognitively healthy participants and 15-25 patients with MCI (age 40-85 years) will be recruited to participate in an exploratory study investigating the association between cognitive functioning and listening effort. Both behavioural and objective measures of listening effort will be investigated. The sentence-final word identification and recall (SWIR) test will be administered with single talker non-intelligible speech background noise while monitoring pupil dilation. Evaluation of cognitive function will be carried out in a clinical setting using a battery of neuropsychological tests. This study is considered exploratory and proof of concept, with information taken to help decide the validity of larger-scale trials. ETHICS AND DISSEMINATION: Written approval exemption was obtained by the Scientific Ethics Committee in the central region of Denmark (De Videnskabsetiske Komiteer i Region Hovedstaden), reference 19042404, and the project is registered pre-results at clinicaltrials.gov, reference NCT04593290, Protocol ID 19042404. Study results will be disseminated in peer-reviewed journals and conferences.

Normative data for Emotion Hexagon test and frequency of impairment in behavioral variant frontotemporal dementia, Alzheimer's disease and Huntington's disease.

Social cognitive functions such as Theory of Mind, empathy and emotion recognition can be impaired in dementia spectrum disorders, especially in diseases with prominent frontal dysfunction. The Emotion Hexagon test (EHT) is a short test of basic emotion recognition. As with other social cognitive tests, normative data for this test is sparse. The aim of this study was to present regression-based normative data for the EHT. Further, we wished to investigate the frequency of impairment in patients with the behavioral variant of frontotemporal dementia (bvFTD, N = 11), Alzheimer's disease (AD, N = 44) and Huntington's disease (HD, N = 52) when using regression-based normative data. The results documented that age (but not gender or education) had a significant effect on EHT score. The effect of age had numerical impact on expected scores in persons older than 60 years. Normative data (including percentile estimates) are presented. The EHT is sensitive to impairment in both bvFTD and HD, where more than 80% of patients had lower scores than expected. In both groups, 54% of patients fell below the 5th percentile-estimate, and in HD 65% fell below the 10th percentile-estimate. In the AD group 25% fell below the 10th percentile-estimate, and 14% fell below the 5th percentile-estimate. In conclusion, very low scores are typically associated with HD and bvFTD, but very poor performances can also be found in other diseases such like AD. Hopefully, the normative data presented and the documentation of their validity in clinical practice is a useful tool for clinicians.

Impaired performances on the category cued memory test in mild Alzheimer's disease and dementia with Lewy bodies: A comparative validity study.

Cued recall taps amnesia of "the hippocampal type" as typically found in Alzheimer's disease (AD). Studies investigating the validity of cued recall measures in AD have typically been conducted in research settings. The Category Cued Memory Test (CCMT-48) measures learning/memory using the same categories during encoding and acquisition. The aim of this study was to investigate how frequently impairments were found on the CCMT-48 mild AD patients from a memory clinic (N = 77). We used a case-oriented approach where individually observed scores were compared to expected scores derived from regressions-based normative data. We also investigated if CCMT-48 performances differed in patients with mild AD and Dementia with Lewy Bodies (DLB) (N = 90). The results showed a significantly higher frequency of impairment in the AD group as compared to the DLB group for scores below 10th percentile-estimate (impaired: AD 88%; DLB 69%) and 5th percentile-estimate (impaired: AD 82%; DLB 53%). In conclusion, a very high frequency of impairment of a picture-based cued recall test in AD patients (very high sensitivity) in a memory clinic setting. However, specificity is not optimal since impairments also frequently occurred in DLB where memory problems could be assumed to be part of attentional deficits and poor retrieval strategies.

Intellectual Curiosity and Action Initiation are Subtypes of Apathy Affected in Huntington Disease Gene Expansion Carriers.

BACKGROUND: Apathy is a prevalent behavioral syndrome of Huntington disease (HD) that can result in severe loss of function for the individual with HD and substantial caregiver distress. Research-based evidence of apathy is characterized by methodological differences, and there is a deficiency in the evidence concerning the subtypes of apathy. OBJECTIVE: To characterize apathy in premanifest and motor-manifest HD gene expansion carriers and controls using the Short Problem Behaviors Assessment for Huntington's Disease (PBA-s) and the Lille Apathy Rating Scale (LARS). METHOD: We included 82 HD gene expansion carriers (premanifest and motor manifest) and 32 controls (Mini-Mental State Examination score ≥24 and Montreal Cognitive Assessment score ≥19) in the study. We quantified apathy using the PBA-s and the LARS and performed correlation analyses between the global LARS score and motor function, cytosine-adenine-guanine repeat length, cytosine-adenine-guanine Age Product score, and neuropsychiatric and cognitive symptoms. RESULTS: The motor-manifest HD gene expansion carriers scored significantly higher than the controls on the global score and the Intellectual Curiosity and Action Initiation subscales of the LARS. Apathy was present in 28% of the HD gene expansion carriers (including 7 premanifest). The apathetic participants had a significantly higher motor score, significantly higher scores on the neuropsychiatric instruments, and significantly lower cognitive scores compared with the controls. CONCLUSION: Apathy is a frequent syndrome that is found in individuals with HD. Apathy has a specific expression, with symptoms such as reduced initiation, voluntary actions, and interests, that might be related to the underlying neuropathology. Apathy is related to disease progression, neuropsychiatric symptoms, and cognitive impairments.

Impairment of Episodic-Specific Autobiographical Memory in Individuals with Subjective Cognitive Decline and in Patients with Prodromal or Mild Alzheimer's Disease.

BACKGROUND: Autobiographical memory (AM) is a personal form of memory that becomes impaired in the early, clinical stages of Alzheimer's disease (AD). In the "preclinical" phase of AD, neuropathological hallmarks are present (especially in a brain network underpinning AM), but performance on standardized neuropsychological tests is normal. Even so, some patients have subjective cognitive decline (SCD). OBJECTIVE: The aim was to 1) investigate AM performance on two tests with different approaches in SCD, and in prodromal and mild AD, and 2) examine the association between the AM tests. METHODS: We included 17 SCD patients with heightened risk of AD, 17 amnestic mild cognitive impairment (aMCI) patients, 17 patients with mild dementia due to AD, and 30 healthy controls. Patients were diagnosed according to international criteria, and all participants had MMSE scores≥24. AM was assessed using the Columbia Autobiographical Memory Interview-Short Form (CAMI-SF) and the Three Events Test. These tests measure the production of contextual details. RESULTS: Significant group effects were found for the Three Events Test and the CAMI-SF. All patient groups produced significantly fewer contextual details than the controls on the Three Events Test. On CAMI-SF, the aMCI and mild AD groups were able to answer fewer questions or gave significantly less detailed answers than the other groups. The SCD patients performed below the controls on CAMI-SF, but the difference was not significant. CONCLUSION: AM may be impaired in very early AD, even in the phases where standardized episodic memory tests show no decline.

Endophenotypical drift in Huntington's disease: a 5-year follow-up study.

BACKGROUND: Huntington's disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission. RESULTS: We found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms. CONCLUSIONS: There is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.

The role of physical and cognitive function in performance of activities of daily living in patients with mild-to-moderate Alzheimer's disease - a cross-sectional study.

BACKGROUND: Several factors may play a role in the ability of patients with Alzheimer's disease to perform activities of daily living (ADL). The aim of this study was to examine the impact of different aspects of physical performance and cognitive functions on ADL in patients suffering from mild-to-moderate Alzheimer's disease. METHODS: We conducted secondary analyses on cross-sectional baseline data from the randomized controlled multicentre study "Preserving quality of life, physical health and functional ability in Alzheimer's Disease: The effect of physical exercise" (ADEX). In total, 185 AD patients (76 women and 109 men), with a mean age on 70,4 years, were included. Data from physical performance tests (Astrand cycle test, Timed up & Go (TUG), Sit to Stand test (STS)) and cognitive tests (Mini Mental Status Examination (MMSE), Symbol Digit Modalities Test (SDMT), Stroop Color and Word test (Stroop)) were used. Their associations with ADL, measured on the ADCS-ADL scale was assessed in multivariable regression analyses. RESULTS: SDMT and MMSE had significant, moderate correlations with total ADL (SDMT: r = 0.33, MMSE: r = 0.42) and instrumental ADL (SDMT: r = 0.31, MMSE: r = 0.42), but not with basic ADL. Adjusting for age and sex, the associations between SDMT and MMSE to total ADL and instrumental ADL persisted. No significant associations were found between Astrand, TUG, STS or Stroop and total ADL, basic ADL or instrumental ADL. CONCLUSION: Total ADL and instrumental ADL are associated with cognitive functions, including executive function. No significant association between examined physical performance parameters and ADL functions was observed, and consequently does not support an impact of physical function on ADL functions in patients with mild-to-moderate Alzheimer's disease and relatively well-preserved physical function. Strategies aimed to improve cognition may be better suited to improve ADL function in patients with mild-to-moderate Alzheimer's disease. TRIAL REGISTRATION: NCT01681602 . Registered 10 September 2012, retrospectively registered.