Journal of Alzheimer's Disease - Volume 48, issue s1

Authors: Tales, Andrea | Jessen, Frank | Butler, Christopher | Wilcock, Gordon | Phillips, Judith | Bayer, Tony

Article Type: Research Article

DOI: 10.3233/JAD-150719

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S1-S3, 2015

Authors: Stone, Jon | Pal, Suvankar | Blackburn, Daniel | Reuber, Markus | Thekkumpurath, Parvez | Carson, Alan

Article Type: Review Article

Abstract: Cognitive symptoms such as poor memory and concentration represent a common cause of morbidity among patients presenting to general practitioners and may result in referral for a neurological opinion. In many cases, these symptoms do not relate to an underlying neurological disease or dementia. In this article we present a personal perspective on the differential diagnosis of cognitive symptoms in the neurology clinic, especially as this applies to patients who seek advice about memory problems but have no neurological disease process. These overlapping categories include the following ‘functional’ categories: 1) cognitive symptoms as part of anxiety or depression; 2) “normal” …cognitive symptoms that become the focus of attention; 3) isolated functional cognitive disorder in which symptoms are outwith ‘normal’ but not explained by anxiety; 4) health anxiety about dementia; 5) cognitive symptoms as part of another functional disorder; and 6) retrograde dissociative (psychogenic) amnesia. Other ‘non-dementia’ diagnoses to consider in addition are 1) cognitive symptoms secondary to prescribed medication or substance misuse; 2) diseases other than dementia causing cognitive disorders; 3) patients who appear to have functional cognitive symptoms but then go on to develop dementia/another neurological disease; and finally 4) exaggeration/malingering. We discuss previous attempts to classify the problem of functional cognitive symptoms, the importance of making a positive diagnosis for the patient, and the need for large cohort studies to better define and manage this large group of patients. Show more

Keywords: Conversion disorder, dissociative amnesia, functional memory disorder, malingering, memory, psychogenic

DOI: 10.3233/JAD-150430

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S5-S17, 2015

Authors: Pennington, Catherine | Hayre, Amrit | Newson, Margaret | Coulthard, Elizabeth

Article Type: Research Article

Abstract: Patients frequently present to the memory clinic with self-reported cognitive symptoms that cannot be attributed to structural, toxic, or metabolic causes, and are out of keeping with their performance on neuropsychological assessment. This can be considered to be Functional (psychosomatic) Cognitive Disorder, which results in significant patient distress and often has a major impact on social functioning and employment. We performed a retrospective analysis of the Bristol ReMemBr group cognitive clinic database to ascertain the prevalence of Functional Cognitive Disorder, review the patient characteristics, and develop new guidelines for diagnosis and management. 196 patients were screened of whom 23 were …diagnosed with Functional Cognitive Disorder; the oldest patient with this diagnosis was aged 60 years at symptom onset. When considering only those presenting below the age of 60 years (total no. held on database = 69), a third were diagnosed with Functional Cognitive Disorder. On neuropsychological testing, 47% had an atypical (invalid) pattern of results, or failed tests of performance validity. Of those with valid neuropsychological results, 80% scored in the normal range. Depression and anxiety were common but did not appear to be the primary cause of cognitive symptoms. Particular characteristics seen were excessively low self-rating of memory ability, and discrepancies between perceived and actual cognitive performance. The rate of unemployment was high, often due to the cognitive symptomatology. This is an important disorder to address, being common in working adults, and carrying a risk of misdiagnosis as early neurodegeneration, with subsequent inappropriate treatment and inclusion in clinical trials. Show more

Keywords: Dementia, mild cognitive impairment, psychological stress, psychosomatic disorders

DOI: 10.3233/JAD-150182

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S19-S24, 2015

Authors: Jenkins, Amy | Tales, Andrea | Tree, Jeremy | Bayer, Antony

Article Type: Research Article

Abstract: Extensive research on the concept of mild cognitive impairment (MCI) as a potential prodromal stage of dementia has highlighted the likelihood that abnormalities in information processing occur at even earlier stages in the disease process with research increasingly focused on the relatively new concept of subjective cognitive impairment (SCI). An individual with SCI will experience cognitive impairment solely on a subjective level, which is in contrast to an individual with MCI who will also experience cognitive impairment at an objective level. SCI is believed to be a risk factor for development of MCI. This qualitative service evaluation aimed to determine …how much is known about SCI and how it is currently managed in specialist clinical practice in the UK. An email-based questionnaire containing a vignette of an individual presenting with SCI was distributed to 112 memory clinics requesting information on their most likely approach to such an individual. The 21% response rate evinces potential time pressure within clinical services that may preclude research participation and/or a lack of issue salience at present. However, the data from those who responded provide an important insight into ‘where we are now’ in relation to this issue. Analysis revealed main themes associated with SCI, namely the factors that influence what action is taken when an individual presents and what further investigations are performed, the multiplicity of potential outcomes experienced, and the barriers clinicians may face. The findings highlight the need for a coherent and consistent framework in relation to the management of SCI. Show more

Keywords: Dementia, health services research, memory clinic, mild cognitive impairment, subjective cognitive impairment

DOI: 10.3233/JAD-150541

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S25-S31, 2015

Authors: Luck, Tobias | Roehr, Susanne | Jessen, Frank | Villringer, Arno | Angermeyer, Matthias C. | Riedel-Heller, Steffi G.

Article Type: Research Article

Abstract: Background: Studies have shown that dementia and cognitive impairment can increase mortality, but less is known about the association between subjectively perceived cognitive deficits (subjective cognitive decline, SCD) and mortality risk. Objective: In this study, we analyzed mortality in non-demented individuals with SCD in a general population sample aged 75+ years. Method: Data were derived from the Leipzig Longitudinal Study of the Aged (LEILA75+). We used the Kaplan-Meier survival method to estimate survival times of individuals with and without SCD and multivariable Cox proportional hazards regression to assess the association between SCD …and mortality risk, controlled for covariates. Results: Out of 953 non-demented individuals at baseline, 117 (12.3% ) expressed SCD. Participants with SCD showed a significantly higher case-fatality rate per 1,000 person-years (114.8, 95% CI = 90.5–145.7 versus 71.7, 95% CI = 64.6–79.5) and a significantly shorter mean survival time than those without (5.4 versus 6.9 years, p  <  0.001). The association between SCD and mortality remained significant in the Cox analysis; SCD increased mortality risk by about 50% (adjusted Hazard Ratio = 1.51) during the study period. Besides SCD, older age, male gender, diabetes mellitus, stroke, and lower global cognitive functioning were also significantly associated with increased mortality. Conclusion: Our findings suggest an increased mortality risk in non-demented older individuals with SCD. Even though further studies are required to analyze potential underlying mechanisms, subjective reports on cognitive deficits may be taken seriously in clinical practice not only for an increased risk of developing dementia and AD but also for a broader range of possible adverse health outcomes. Show more

Keywords: Dementia, epidemiology, mortality, subjective cognitive decline

DOI: 10.3233/JAD-150090

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S33-S42, 2015

Authors: Tandetnik, Caroline | Farrell, Meagan T. | Cary, Mark S. | Cines, Sarah | Emrani, Sheina | Karlawish, Jason | Cosentino, Stephanie

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) is increasingly considered promising to detect preclinical Alzheimer’s disease. How SCD is ascertained is critical for determining its potential utility in identifying at-risk individuals, yet SCD measures differ along several dimensions. Objective: We aimed to examine the extent to which reports of SCD in healthy elderly may be influenced by the characteristics of the SCD measures. We investigated variations in rates of SCD endorsement across different measures, including an open-ended question. We also examined the association of responses across measures, and the degree to which specific SCD items were associated with objective …memory performance. Methods: 99 healthy elderly completed a series of questionnaires from which 10 items examining SCD for memory and other aspects of cognition were drawn. We applied Cochran’s Q tests to assess differences in rates of SCD, correlation analyses to examine association of SCD responses, and regression models to determine the association between SCD items and delayed verbal memory. Results: Rates of SCD varied as a function of the assessment format, ranging from 1 to 7% for memory and 5 to 20% for concentration. SCD was lower for memory versus non-memory domains. SCD items were associated both within and across domains. The most accurate predictor of memory was memory-related SCD in comparison to others the same age. Conclusion: Characteristics of SCD items influence rates of endorsement. Querying SCD using an “age-anchored” question may provide the most accurate reflection of actual cognitive performance. Show more

Keywords: Aging, cognitive complaints, early detection, metacognition, subjective cognitive decline, subjective memory complaints

DOI: 10.3233/JAD-150251

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S43-S55, 2015

Authors: Dalla Barba, Gianfranco | La Corte, Valentina | Dubois, Bruno

Article Type: Research Article

Abstract: The clinical challenge in subjective memory decline (SMD) is to identify which individuals will present memory deficits. Since its early description from Babinsky, who coined the term ‘anosognosia’ (i.e., the lack of awareness of deficit), the awareness of cognitive impairment is crucial in clinical neuropsychology. We propose a cognitive model in which SMD and anosognosia can be considered two opposite forms of distorted awareness of cognitive performance and can be accounted for within a model in which consciousness of memory performance can vary in a continuum from normal awareness of performance (preserved or impaired) to anosognosia through a disorder of …consciousness related to SMD that we call “cognitive dysgnosia”, i.e., awareness of normal performance as impaired. This model suggests that the neuropsychological assessment of memory performance should always be coupled with a deep evaluation of awareness of the subject’s memory profile, which allow to better identify the disorder of consciousness with or without cognitive impairment. In this line, it seems necessary to develop more sensitive neuropsychological tools in order to discriminate, within the SMD, individuals who are likely to develop clinical Alzheimer’s disease from those whose memory decline complaint is not associated with an underlyingneurodegenerative pathology. Show more

Keywords: Alzheimer’s disease, awareness, consciousness, memory, subjective cognitive decline

DOI: 10.3233/JAD-150141

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S57-S61, 2015

Authors: Rabin, Laura A. | Smart, Colette M. | Crane, Paul K. | Amariglio, Rebecca E. | Berman, Lorin M. | Boada, Mercé | Buckley, Rachel F. | Chételat, Gaël | Dubois, Bruno | Ellis, Kathryn A. | Gifford, Katherine A. | Jefferson, Angela L. | Jessen, Frank | Katz, Mindy J. | Lipton, Richard B. | Luck, Tobias | Maruff, Paul | Mielke, Michelle M. | Molinuevo, José Luis | Naeem, Farnia | Perrotin, Audrey | Petersen, Ronald C. | Rami, Lorena | Reisberg, Barry | Rentz, Dorene M. | Riedel-Heller, Steffi G. | Risacher, Shannon L. | Rodriguez, Octavio | Sachdev, Perminder S. | Saykin, Andrew J. | Slavin, Melissa J. | Snitz, Beth E. | Sperling, Reisa A. | Tandetnik, Caroline | van der Flier, Wiesje M. | Wagner, Michael | Wolfsgruber, Steffen | Sikkes, Sietske A.M. | the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844–852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 …countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures— approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes. Show more

Keywords: Cognition, cognitive complaints, dementia, early detection, memory complaints, subjective cognition, mild cognitive impairment, preclinical Alzheimer’s disease, questionnaire, subjective cognitive impairment, subjective memory complaints

DOI: 10.3233/JAD-150154

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S63-S86, 2015

Authors: Valech, Natalia | Mollica, María A. | Olives, Jaume | Tort, Adriá | Fortea, Juan | Lleo, Alberto | Belén, Sánchez-Saudinós | Molinuevo, José Luis | Rami, Lorena

Article Type: Research Article

Abstract: Background: Self-reported and informant-reported subjective cognitive decline (SCD) may be useful in the detection of preclinical Alzheimer’s disease (Pre-AD) and cognitive impairment related to abnormal amyloid-β (Aβ 42 ) levels. Objectives: a) To compare the Subjective Cognitive Decline Questionnaire (SCD-Q) ratings between Pre-AD subjects and cognitively healthy controls, b) to study the association of SCD-Q scores with levels of AD biomarkers in cognitively healthy and cognitively impaired subjects, and c) to compare SCD-Q ratings in cognitively impaired subjects with or without abnormal Aβ 42 . Methods: Two hundred and seventeen participants (111 subjects; 106 informants) …answered the SCD-Q. All subjects underwent a lumbar puncture to determine levels of Aβ 42 and tau, and an extensive neuropsychological battery. Healthy subjects were classified as Controls (CTR) or Pre-AD according to the absence or the presence of abnormal Aβ 42 , and those with cognitive impairment (CI) into Non-amyloid (NonAB-CI) or Amyloid (AB-CI) impairment. Results: Informants’ SCD-Q scores were significantly higher in the Pre-AD group than in the CTR group (F = 6.75; p  = 0.01). No significant differences were found in self-ratings. In the cognitively impaired groups, there were no significant differences in the SCD-Q ratings. In the whole sample, informants’ ratings of SCD-Q correlated with Aβ 42 (r  = –0.21; p  = 0.02) and tau levels (r  = 0.28; p  = 0.00). Conclusions: Higher informants’ ratings of SCD-Q differentiated Pre-AD subjects from CTR. Informants’ ratings of SCD-Q correlated weakly with cerebrospinal fluid AD biomarkers. Show more

Keywords: Amyloid-β, preclinical Alzheimer’s disease, subjective cognitive decline, tau proteins

DOI: 10.3233/JAD-150117

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S87-S98, 2015

Authors: Rodríguez-Gómez, Octavio | Abdelnour, Carla | Jessen, Frank | Valero, Sergi | Boada, Merçé

Article Type: Review Article

Abstract: Subjective cognitive decline (SCD) has been proposed as a marker of neurodegeneration in cognitively normal elderly. This idea is supported by the growing evidence that SCD is associated with Alzheimer’s disease (AD) biomarkers and increases the risk of future cognitive impairment. Nevertheless, this evidence is not complete, since other studies have not found these associations. This discrepancy could have a methodological basis. It is well known that across the broad spectrum of degenerative disease from healthy controls to dementia, the research setting affects key characteristics of the sample such as age, educational level, or family history of dementia. However, virtually …no studies have specifically tested the influence of sampling and recruitment methods in SCD research. Population-based samples are less biased and therefore they probably are more suitable for the study of memory complaints as a symptom at the population level. On the other hand, the memory clinic setting could introduce a set of biases that make these patients more likely to develop cognitive impairment. Thus, memory clinic would be the most cost-effective context in which to study the phenomenology of SCD due to AD and eventually recruit patients for secondary prevention trials. However, this general hypothesis needs to be tested. Studies that compare samples of patients with SCD from different settings are necessary. Sometimes it is difficult for patients with subtle forms of cognitive impairment to access specialized diagnostic centers. Based in our experience we state that Open House type initiatives may be useful for attracting these individuals to memory clinics. Show more

Keywords: Alzheimer’s disease, epidemiologic research design, epidemiologic studies, patient selection, risk, sampling, selection bias, subjective cognitive decline

DOI: 10.3233/JAD-150189

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S99-S107, 2015