Faculty Bibliography
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326
IS AGING A DISEASE? SUBJECTIVE COGNITIVE IMPAIRMENT AND PHYSIOLOGIC FACTORS [Meeting Abstract]
ISI:000408541600028
ISSN: 1064-7481
CID: 2975352
Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures used Across 19 International Research Studies
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.
PMCID:4617342
PMID: 26402085
ISSN: 1875-8908
CID: 1786922
Dementia service centres in Austria: A comprehensive support and early detection model for persons with dementia and their caregivers - theoretical foundations and model description
Despite the highly developed social services in Austria, the County of Upper Austria, one of the nine counties of Austria had only very limited specialized services for persons with dementia and their caregivers in 2001. Support groups existed in which the desire for more specialized services was voiced. In response to this situation, funding was received to develop a new structure for early disease detection and long term support for both the person with dementia and their caregivers. This article describes the development of the model of the Dementia Service Centres (DSCs) and the successes and difficulties encountered in the process of implementing the model in six different rural regions of Upper Austria. The DSC was described in the First Austrian Dementia Report as one of the potential service models for the future.
PMCID:4514820
PMID: 24339114
ISSN: 1471-3012
CID: 895862
Effects of a comprehensive, individualized person-centered management program on persons with moderately severe Alzheimer's disease: A randomized controlled trial-comprehensive study findings [Meeting Abstract]
Background: Persons with moderately severe AD are the most distressed AD persons (Reisberg, et al., Bull Clin Neurosci, 1989). We described some needs and potential solutions for these persons in a "science of AD management" (Reisberg, et al., Am J Alzheimers Dis Other Demen, 2002). Subsequently, memantine, the first medication for advanced AD, demonstrated efficacy. We therefore investigated a Comprehensive Individualized Person Centered Management Program (CI-PCM) in addition to memantine treatment, in moderately severe AD persons. Methods: This was a 28 week, randomized, blinded, parallel group study in which 20 probable AD subjects (MMSE range = 3 - 14; Global Deterioration Scale [GDS] stage 5 or 6), with basic activity of daily living (ADL) deficits (Functional Assessment Staging [FAST] scale stages > 6a), were randomly assigned to: (1) the CI-PCM program with memantine treatment or (2) memantine treatment alone. The CI-PCM program included home visits, caregiver training and support groups. Results for one primary outcome, the NYU CIBICPlus, have previously been reported. We now report outcomes for the other assessments (see Tables 1 to 3). Results: Ten subjects were randomized to each treatment condition. All completed the study. Endpoint results are reported herein (Tables 1 to 3). Both ADL assessments (the ADCS-ADLsev abr. and the FAST-DS) showed significant effects (p < 0.01) in favor of the CI-PCM subject group. Both behavioral assessments (the BEHAVE-AD-FW and the RMBPC) also showed significant disturbance reductions in the CI-PCM subjects (p = 0.001 and p < 0.05, respectively). Neither cognitive assessment (the SIB or the MMSE) showed significant between group differences. Conclusions: The present results are consonant with observations we previously reported with the NYU CIBIC-Plus in which subscale analyses also indicated robust effects of the CI-PCM intervention on functioning and behavior, but not cognition. The NYU CIBIC-Plus clinician raters were different from and blind to the raters' evaluations of the results reported herein. Hence, it is clear that the CI-PCM program, from multiple rater perspectives, and multiple assessments, produces robust positive effects on functioning and behavior. These results are of great potential significance for AD persons and their caregivers. (Table presented)
EMBASE:72125165
ISSN: 1552-5260
CID: 1923972
Evidence for affective symptoms as an early manifestation of cognitive change [Meeting Abstract]
'Subjective Cognitive Impairment' (SCI) persons have the subjective belief that memory is impaired, but show normal performance on psychometric tests. In this study, we aim to assess the nature of cognitive and affective symptoms of SCI, and develop tools to identify early predictors of cognitive decline in the evolution towards MCI and AD. METHOD: 136 healthy subjects, aged > 50 years, presenting at the NYU Alzheimer's Disease Center were evaluated through self-reported scales : A Visual Analog Scale (VAS), (Guillo Benarous, 2013), the Brief Questionnaire Regarding Severity of Memory & Emotional Problems (BQRS-M&E =S1), (Reisberg, 2013), and the Memory Complaint Questionnaire (MAC-Q). Alternating subjects were evaluated on time related scales: the ADNI Cognitive Change Index =S2 (Saykin, 2012), the Sahlgrenska Academy Self-Reported Cognitive Impairment Questionnaire (SASCI-Q = S5) or on a severity based questionnaire SEVCOG =S3 and an Emotional Questionnaire =S4; on depression and anxiety scales: Geriatric Depression Scale, Hamilton; and on psychometric measures: MMSE, Logic1, Digit Span F&B, TMT, DSST, Paired Associates Recall and the Boston Naming Test. The evaluations at baseline were studied. RESULTS: Very few significant relationships are found between objective testing and subjective evaluations. We found a robust correlation between depression scales and all of the subjective self-reported scales, stronger with severity based self-reported scales. CONCLUSION: Affective symptoms might be early indicators of cognitive and associated physiologic brain changes and could point to prevention strategies. (Table Presented)
EMBASE:71854032
ISSN: 1660-2854
CID: 1560382
Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States
Importance: Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States. Objective: To determine the frequency of the APP A673T variant in a large group of elderly cognitively normal controls and AD cases from the United States and in 2 case-control cohorts from Sweden. Design, Setting, and Participants: Case-control association analysis of variant APP A673T in US and Swedish white individuals comparing AD cases with cognitively intact elderly controls. Participants were ascertained at multiple university-associated medical centers and clinics across the United States and Sweden by study-specific sampling methods. They were from case-control studies, community-based prospective cohort studies, and studies that ascertained multiplex families from multiple sources. Main Outcomes and Measures: Genotypes for the APP A673T variant were determined using the Infinium HumanExome V1 Beadchip (Illumina, Inc) and by TaqMan genotyping (Life Technologies). Results: The A673T variant genotypes were evaluated in 8943 US AD cases, 10 480 US cognitively normal controls, 862 Swedish AD cases, and 707 Swedish cognitively normal controls. We identified 3 US individuals heterozygous for A673T, including 1 AD case (age at onset, 89 years) and 2 controls (age at last examination, 82 and 77 years). The remaining US samples were homozygous for the alanine (A673) allele. In the Swedish samples, 3 controls were heterozygous for A673T and all AD cases were homozygous for the A673 allele. We also genotyped a US family previously reported to harbor the A673T variant and found a mother-daughter pair, both cognitively normal at ages 72 and 84 years, respectively, who were both heterozygous for A673T; however, all individuals with AD in the family were homozygous for A673. Conclusions and Relevance: The A673T variant is extremely rare in US cohorts and does not play a substantial role in risk for AD in this population. This variant may be primarily restricted to Icelandic and Scandinavian populations.
PMCID:4324097
PMID: 25531812
ISSN: 2168-6149
CID: 1416202
Cognitive-Motor Intervention in Alzheimer's Disease: Long-Term Results from the Maria Wolff Trial
Background: Little is known about the long-term acceptance and effects of cognitive and motor stimulation interventions (CMSI) in Alzheimer's disease (AD). Objective: To evaluate a replicable CMSI program for mild cognitive impairment (MCI) and mild-to-moderate AD persons. Methods: Eighty-four non-institutionalized subjects with AD were randomized to receive either CMSI, administered by a single care provider, or standard support. Cognition, activities of daily living (ADL), mood, and study partner's subjective burden were assessed by blinded raters. Data on institutionalization, psychiatric medications, and demise were collected by the study physicians. Random effects model and survival analyses were conducted, after 2 and 3 years of study. Results: Three-year assessments could be performed by the physician in 85% and by the blinded rater in 66% of subjects. Significant benefits were observed in basic ADL at the 2- and 3-year assessments, whereas instrumental ADL showed benefits only up to the second year of intervention (p < 0.05). Conclusion: Long-term cognitive-motor stimulation is well accepted and produces functional benefits in subjects with AD, with no extra subjective burden in the partner.
PMID: 25547632
ISSN: 1387-2877
CID: 1419892
Neuropsychological and Neuropsychiatric Prediction of Global Cognitive Status Among Older Spanish-Speaking Hispanics and English-Speaking Whites
BACKGROUND: Neuropsychological and depression measures have been found to predict cognitive functioning. We compared these associations among whites and Spanish-speaking Hispanics. METHODS: Fifty-two pairs of whites and Hispanics were matched demographically and clinically in a cross-sectional study. Hierarchical regression analyses predicted Global Deterioration Scale (GDS) rating by baseline neuropsychological tests and depression symptoms. RESULTS: Neuropsychological tests predicted GDS better in whites; depression symptoms-specifically retardation-predicted well in Hispanics but not whites. Immediate recall of the New York University (NYU)-Paragraph Test and the Retardation item of the Hamilton Depression Rating Scale were associated with GDS in Hispanics and delayed recall of the NYU-Paragraph Test and Wechsler Adult Intelligence Scale-Digit Symbol in whites. Neuropsychological tests and depression symptoms predicted GDS differently in Hispanics and whites. DISCUSSION: These results suggest that other measures should be considered to increase the predictive accuracy of neuropsychological tests when assessing cognitive status in Spanish-speaking Hispanics. Additional studies of specific ethnic/racial and sociodemographic subgroups are warranted.
PMCID:4465291
PMID: 24759088
ISSN: 0891-9887
CID: 948142
A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease
There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.
PMCID:4317324
PMID: 24798886
ISSN: 1552-5260
CID: 956732
Effects of multiple genetic Loci on age at onset in late-onset Alzheimer disease: a genome-wide association study
IMPORTANCE: Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants. OBJECTIVES: To investigate the effects of known Alzheimer disease risk loci in modifying AAO and to estimate their cumulative effect on AAO variation using data from genome-wide association studies in the Alzheimer Disease Genetics Consortium. DESIGN, SETTING, AND PARTICIPANTS: The Alzheimer Disease Genetics Consortium comprises 14 case-control, prospective, and family-based data sets with data on 9162 participants of white race/ethnicity with Alzheimer disease occurring after age 60 years who also had complete AAO information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single-nucleotide polymorphisms most significantly associated with risk at 10 confirmed LOAD loci were examined in linear modeling of AAO, and individual data set results were combined using a random-effects, inverse variance-weighted meta-analysis approach to determine whether they contribute to variation in AAO. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. MAIN OUTCOMES AND MEASURES: Age at disease onset abstracted from medical records among participants with LOAD diagnosed per standard criteria. RESULTS: Analysis confirmed the association of APOE with earlier AAO (P = 3.3 x 10-96), with associations in CR1 (rs6701713, P = 7.2 x 10-4), BIN1 (rs7561528, P = 4.8 x 10-4), and PICALM (rs561655, P = 2.2 x 10-3) reaching statistical significance (P < .005). Risk alleles individually reduced AAO by 3 to 6 months. Burden analyses demonstrated that APOE contributes to 3.7% of the variation in AAO (R2 = 0.256) over baseline (R2 = 0.221), whereas the other 9 loci together contribute to 2.2% of the variation (R2 = 0.242). CONCLUSIONS AND RELEVANCE: We confirmed an association of APOE (OMIM 107741) variants with AAO among affected participants with LOAD and observed novel associations of CR1 (OMIM 120620), BIN1 (OMIM 601248), and PICALM (OMIM 603025) with AAO. In contrast to earlier hypothetical modeling, we show that the combined effects of Alzheimer disease risk variants on AAO are on the scale of, but do not exceed, the APOE effect. While the aggregate effects of risk loci on AAO may be significant, additional genetic contributions to AAO are individually likely to be small.
PMCID:4314944
PMID: 25199842
ISSN: 2168-6149
CID: 1348572
