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Sleep-wake disorders in Alzheimer’s disease: further genetic analyses in relation to objective sleep measures
- Jerome A. Yesavage, Art Noda, Alesha Heath, M. Windy McNerney, Benjamin W. Domingue, Yozen Hernandez, Gary Benson, Joachim Hallmayer, Ruth O’Hara, Leanne M. Williams, Andrea N. Goldstein-Piekarski, Jamie M. Zeitzer, J. Kaci Fairchild
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- Journal:
- International Psychogeriatrics / Volume 32 / Issue 7 / July 2020
- Published online by Cambridge University Press:
- 19 November 2019, pp. 807-813
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This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer’s disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.
Is it time to revise the diagnostic criteria for apathy in brain disorders? The 2018 international consensus group
- P. Robert, K.L. Lanctôt, L. Agüera-Ortiz, P. Aalten, F. Bremond, M. Defrancesco, C. Hanon, R. David, B. Dubois, K. Dujardin, M. Husain, A. König, R. Levy, V. Mantua, D. Meulien, D. Miller, H.J. Moebius, J. Rasmussen, G. Robert, M. Ruthirakuhan, F. Stella, J. Yesavage, R. Zeghari, V. Manera
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- Journal:
- European Psychiatry / Volume 54 / October 2018
- Published online by Cambridge University Press:
- 17 July 2018, pp. 71-76
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Background:
Apathy is a very common behavioural and psychological symptom across brain disorders. In the last decade, there have been considerable advances in research on apathy and motivation. It is thus important to revise the apathy diagnostic criteria published in 2009. The main objectives were to: a) revise the definition of apathy; b) update the list of apathy dimensions; c) operationalise the diagnostic criteria; and d) suggest appropriate assessment tools including new technologies.
Methods:The expert panel (N = 23) included researchers and health care professionals working on brain disorders and apathy, a representative of a regulatory body, and a representative of the pharmaceutical industry. The revised diagnostic criteria for apathy were developed in a two-step process. First, following the standard Delphi methodology, the experts were asked to answer questions via web-survey in two rounds. Second, all the collected information was discussed on the occasion of the 26th European Congress of Psychiatry held in Nice (France).
Results:Apathy was defined as a quantitative reduction of goal-directed activity in comparison to the patient’s previous level of functioning (criterion A). Symptoms must persist for at least four weeks, and affect at least two of the three apathy dimensions (behaviour/cognition; emotion; social interaction; criterion B). Apathy should cause identifiable functional impairments (criterion C), and should not be fully explained by other factors, such as effects of a substance or major changes in the patient’s environment (Criterion D).
Table 1 Apathy diagnostic criteria 2018. CRITERION A: A quantitative reduction of goal-directed activity either in behavioral, cognitive, emotional or social dimensions in comparison to the patient’s previous level of functioning in these areas. These changes may be reported by the patient himself/herself or by observation of others. CRITERION B: The presence of at least 2 of the 3 following dimensions for a period of at least four weeks and present most of the time B1. BEHAVIOUR & COGNITION Loss of, or diminished, goal-directed behaviour or cognitive activity as evidenced by at least one of the following: General level of activity: the patient has a reduced level of activity either at home or work, makes less effort to initiate or accomplish tasks spontaneously, or needs to be prompted to perform them. Persistence of activity: He/she is less persistent in maintaining an activity or conversation, finding solutions to problems or thinking of alternative ways to accomplish them if they become difficult. Making choices: He/she has less interest or takes longer to make choices when different alternatives exist (e.g., selecting TV programs, preparing meals, choosing from a menu, etc.) Interest in external issue: He/she has less interest in or reacts less to news, either good or bad, or has less interest in doing new things Personal wellbeing: He/she is less interested in his/her own health and wellbeing or personal image (general appearance, grooming, clothes, etc.). B2. EMOTION Loss of, or diminished, emotion as evidenced by at least one of the following: Spontaneous emotions: the patient shows less spontaneous (self-generated) emotions regarding their own affairs, or appears less interested in events that should matter to him/her or to people that he/she knows well. Emotional reactions to environment: He/she expresses less emotional reaction in response to positive or negative events in his/her environment that affect him/her or people he/she knows well (e.g., when things go well or bad, responding to jokes, or events on a TV program or a movie, or when disturbed or prompted to do things he/she would prefer not to do). Impact on others: He/she is less concerned about the impact of his/her actions or feelings on the people around him/her. Empathy: He/she shows less empathy to the emotions or feelings of others (e.g., becoming happy or sad when someone is happy or sad, or being moved when others need help). Verbal or physical expressions: He/she shows less verbal or physical reactions that reveal his/her emotional states. B3. SOCIAL INTERACTION Loss of, or diminished engagement in social interaction as evidenced by at least one of the following: Spontaneous social initiative: the patient takes less initiative in spontaneously proposing social or leisure activities to family or others. Environmentally stimulated social interaction: He/she participates less, or is less comfortable or more indifferent to social or leisure activities suggested by people around him/her. Relationship with family members: He/she shows less interest in family members (e.g., to know what is happening to them, to meet them or make arrangements to contact them). Verbal interaction: He/she is less likely to initiate a conversation, or he/she withdraws soon from it Homebound: He /She prefer to stays at home more frequently or longer than usual and shows less interest in getting out to meet people. CRITERION C These symptoms (A - B) cause clinically significant impairment in personal, social, occupational, or other important areas of functioning. CRITERION D The symptoms (A - B) are not exclusively explained or due to physical disabilities (e.g. blindness and loss of hearing), to motor disabilities, to a diminished level of consciousness, to the direct physiological effects of a substance (e.g. drug of abuse, medication), or to major changes in the patient’s environment. Conclusions:The new diagnostic criteria for apathy provide a clinical and scientific framework to increase the validity of apathy as a clinical construct. This should also help to pave the path for apathy in brain disorders to be an interventional target.
Verbal Naming Test for Use with Older Adults: Development and Initial Validation
- Brian P. Yochim, Sherry A. Beaudreau, J. Kaci Fairchild, Maya V. Yutsis, Neda Raymond, Leah Friedman, Jerome Yesavage
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- Journal:
- Journal of the International Neuropsychological Society / Volume 21 / Issue 3 / March 2015
- Published online by Cambridge University Press:
- 24 March 2015, pp. 239-248
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Naming or word-finding tasks are a mainstay of the typical neuropsychological evaluation, particularly with older adults. However, many older adults have significant visual impairment and there are currently no such word-finding tasks developed for use with older visually impaired populations. This study presents a verbal, non-visual measure of word-finding for use in the evaluation of older adults with possible dysnomia. Stimuli were chosen based on their frequency of usage in everyday spoken language. A 60-item scale was created and given to 131 older Veterans. Rasch analyses were conducted and differential item functioning assessed to eliminate poorly-performing items. The final 55-item scale had a coefficient alpha of 0.84 and correlated with the Neuropsychological Assessment Battery Naming test, r=0.84, p<.01, Delis-Kaplan Executive Function System (D-KEFS) Category Fluency, r=0.45, p<.01, and the D-KEFS Letter Fluency, r=0.40, p<.01. ROC analyses found the measure to have sensitivity of 79% and specificity of 85% for detecting dysnomia. Patients with dysnomia performed worse on the measure than patients with intact word-finding, t(84)=8.2, p<.001. Patients with no cognitive impairment performed significantly better than patients with mild cognitive impairment, who performed significantly better than patients with dementia. This new measure shows promise in the neuropsychological evaluation of word-finding ability in older adults with or without visual impairment. Future directions include the development of a shorter version and the generation of additional normative data. (JINS, 2015, 21, 1–10)
Which older adults maintain benefit from cognitive training? Use of signal detection methods to identify long-term treatment gains
- J. K. Fairchild, L. Friedman, A. C. Rosen, J. A. Yesavage
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- Journal:
- International Psychogeriatrics / Volume 25 / Issue 4 / April 2013
- Published online by Cambridge University Press:
- 14 December 2012, pp. 607-616
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Background: Cognitive training has been shown to improve memory in older adults; however, little is known about which individuals benefit from or respond best to training in the long term. Identification of responders’ characteristics would help providers match cognitive interventions to individuals to improve their effectiveness. Signal detection methods may prove more informative than more commonly used analytic methods. The goal of the current study is to identify baseline characteristics of long-term treatment responders and of those able to maintain their initial benefit from cognitive training.
Methods: Participants were 120 non-demented, community-dwelling older adults who had participated in a cognitive training intervention. Tested predictors included both demographic and neurocognitive variables. Primary outcome variables were performance on measures of memory at one-year follow-up.
Results: Results of the signal detection analysis indicated that different neurocognitive performances predicted long-term effects of memory training and maintenance of initial treatment response according to different types of to-be-remembered material. Higher baseline scores on tests of associative memory, delayed verbal memory, attention, episodic memory, and younger age were found predictive of long-term response one year later. Higher associative memory scores and lower initial gains at the end of treatment (week 14) predicted successful maintenance of training gains at week 52.
Conclusions: To derive long-term benefit from particular cognitive training programs, it appears necessary for older adults to have specific neurocognitive profiles. Further, inclusion of booster sessions to cognitive training programs may assist in maintenance of initial treatment gains.
Adjusting Mini-Mental State Examination Scores for Age and Educational Level to Screen for Dementia: Correcting Bias or Reducing Validity?
- Helena Chmura Kraemer, Deborah J. Moritz, Jerome Yesavage
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- International Psychogeriatrics / Volume 10 / Issue 1 / March 1998
- Published online by Cambridge University Press:
- 10 January 2005, pp. 43-51
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The question of whether Mini-Mental State Examination scores should be adjusted for age and educational levels to screen for dementia in clinical populations is reexamined in the results of a recent study supporting adjustment. If the criterion is to identify the most accurate screening procedure for each sociodemographic subgroup, the evidence indicates that the unadjusted scores are preferable. Other criteria might lead to different conclusions. The validities of some of these criteria are questionable because they have the flaw that they are easily satisfied by using random decision procedures.