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

Authors: Archer, Hilary Anne | Newson, Margaret Anne | Coulthard, Elizabeth Jane

Article Type: Review Article

Abstract: Subjective memory complaints (SMC) are important and may, in certain individuals, herald the onset of neurodegenerative diseases such Alzheimer’s disease. However, they are very common and in some individuals will result from mood disorders/personality factors or systemic illnesses. Research has been hampered by the wide variety of criteria and neuropsychological tests used to define this disorder. Different terminology has also hindered the ability to generate generalizable results. We evaluate how subjects with SMC are defined within different research settings (community, primary care, and memory clinic), their rates of progression to mild cognitive impairment and dementia, and how individuals within these …contexts differ in terms of complaints, personal characteristics, and help-seeking behavior. Show more

Keywords: Alzheimer’s disease, complaints, memory, subjective, setting

DOI: 10.3233/JAD-150108

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S109-S114, 2015

Authors: Yates, Jennifer A. | Clare, Linda | Woods, Robert T. | Matthews, Fiona E. | and the Cognitive Function and Ageing Study Wales

Article Type: Research Article

Abstract: Subjective memory complaints (SMC) are a criterion in many definitions of mild cognitive impairment (MCI). However, there is controversy over whether this is useful and appropriate, as previous research has suggested that SMC may be a function of mood problems such as anxiety and depression. This paper aimed to establish the relationship between MCI and mood in older people and to investigate the role that SMC play in the relationship. Structured interviews were conducted with community dwelling older people in Wales to collect information regarding cognitive functioning, mood, and well-being. A widely-used algorithm was used to categorize 3,173 participants into …three groups: not cognitively impaired, MCI including SMC (MCI), and MCI without SMC (MCIW). The odds of experiencing anxiety or depression were calculated for each cognitive group. Participants with MCI had increased odds of experiencing symptoms of both anxiety and depression, but the odds were not changed for participants in the not cognitively impaired or MCIW categories. A mediation analysis was performed on the whole sample using cognition as a dichotomous variable, grouped using an age-, education-, and gender-adjusted median cut off point. This showed that SMC partially mediated the relationship between anxiety and cognition, and depression and cognition. Mood problems may be related to SMC rather than objective cognitive impairment, as only participants with MCI that included SMC showed increased odds of experiencing anxiety and depression. SMC are likely to play a mediating role in the relationship between mood and cognitive functioning. Show more

Keywords: Anxiety, depression, memory, mild cognitive impairment

DOI: 10.3233/JAD-150371

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S115-S123, 2015

Authors: Buckley, Rachel F. | Saling, Michael M. | Frommann, Ingo | Wolfsgruber, Steffen | Wagner, Michael

Article Type: Research Article

Abstract: Background: Subjective cognitive decline is related to greater risk of dementia and biological markers of Alzheimer’s disease (AD), but researchers are yet to characterize the phenomenological perspective of cognitive decline in those with and without a diagnosis of AD. Objective: To collate and synthesize studies measuring the subjective experience of cognitive change or decline in healthy older adults and those with mild cognitive impairment and AD. Methods: We reviewed 58 peer-reviewed articles that were found to directly or indirectly refer to the subjective experience of cognitive decline. Results: We …extracted eight central themes, dealing with cognitive changes experienced by each diagnostic group, and also related to issues of changing self-identity, the causal attribution of cognitive decline, the anxiety and concern related to perceived decline, the negative perceptions attached to a diagnosis of dementia, changing levels of insight, and perception of well-being in aging. Conclusion: This review is the first step toward characterizing phenomenological profiles of cognitive change in both non-demented and demented older adults. Developing a clearer understanding of subjective cognitive decline, particularly at the earliest stages of AD, will augment the sensitivity of detection of individuals at greater risk of future dementia. Show more

Keywords: Alzheimer’s disease, mild cognitive impairment, qualitative, subjective cognitive decline, subjective memorycomplaint

DOI: 10.3233/JAD-150095

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S125-S140, 2015

Authors: Perrotin, Audrey | de Flores, Robin | Lamberton, Franck | Poisnel, Géraldine | La Joie, Renaud | de la Sayette, Vincent | Mézenge, Florence | Tomadesso, Clémence | Landeau, Brigitte | Desgranges, Béatrice | Chételat, Gaël

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) may be the first clinical sign of Alzheimer’s disease (AD). SCD individuals with normal cognition may already have significant hippocampal atrophy, a well-known feature of AD. Objective: To test the hypothesis that SCD, compared to healthy individuals without SCD, have a pattern of hippocampal subfield atrophy similar to that measured in the AD pathology. Methods: 17 SCD, 21 AD, and 40 matched controls underwent a standard T1-weighted MRI and a dedicated high-resolution MRI proton-density hippocampal sequence. For each participant, three hippocampal regions-of-interest were manually delineated on the proton-density hippocampal sequence …corresponding to the CA1, subiculum, and other (including CA2-3-4 and dentate gyrus) subfields. Total intracranial volume (TIV)-normalized subfield volumes were compared between-group. Voxelwise group comparisons assessed from the standard T1 MRI were also projected on 3D hippocampal surface views. Results: Both patient groups showed significant TIV-normalized volume decrease in hippocampus global volume and in CA1 and subiculum subfields as well as in the other subfield in AD compared to controls. Significant differences were observed between SCD and AD in hippocampus global TIV-normalized volume. Atrophy maps on hippocampal surface showed major involvement of the lateral part (CA1) in both SCD and AD, with larger overlap of other regions in AD. Conclusion: The findings indicate topographically similar hippocampal subfield changes in SCD individuals as those found in AD. This further highlights the relevance of SCD recruited from a memory clinic in assessing predementia AD stages. Show more

Keywords: Alzheimer’s disease, hippocampal subfields, hippocampus, magnetic resonance imaging, subjective cognitive decline

DOI: 10.3233/JAD-150087

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S141-S150, 2015

Authors: Snitz, Beth E. | Lopez, Oscar L. | McDade, Eric | Becker, James T. | Cohen, Ann D. | Price, Julie C. | Mathis, Chester A. | Klunk, William E.

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) in otherwise normal aging may be identified via symptom inventories in a research setting (‘questionnaire-discovered complaints’) or via patients seeking evaluation/services in a clinical setting (‘presenting complainers’). Most studies of SCD and amyloid-β (Aβ) imaging to date have used the former approach, with inconsistent results. Objective: To test whether ‘presenting SCD’ participants in an academic memory clinic setting show increased brain Aβ deposition on imaging. Methods: Fourteen patients (mean age 68.1, SD 4.0 years) diagnosed with subjective cognitive complaints with normal neuropsychological testing were recruited into a …Pittsburgh compound B (PiB)-PET study. Detailed self-report inventories and additional cognitive tests were administered. Results were compared to a reference cohort of cognitively normal volunteers (NC) from an independent neuroimaging study (mean age 73.6, SD 5.8 years). Results: 57% (8/14) of SCD participants were PiB-positive by a sensitive, regionally-based definition, compared to 31% (26/84) of the NC cohort. SCD participants had significantly higher PiB retention (SUVR) than NC in three of six regions of interest: frontal cortex (p  = 0.02), lateral temporal cortex (p  = 0.02), and parietal cortex (p  = 0.04). SCD participants showed measurable deviations on questionnaires reflecting high negative affect (i.e., depressive symptoms and neuroticism). Findings were suggestive that deficits on verbal associative binding may be specific to Aβ-positive versus Aβ-negative SCD. Conclusion: Older participants with SCD presenting to a memory clinic in this pilot study sample have higher brain Aβ deposition compared to normal aging study volunteers unselected on complaints. Further study of presenting SCD are warranted to determine the prognostic significance of Aβ deposition in this context. Show more

Keywords: Amyloid-β protein, cognition, memory, positron-emission tomography

DOI: 10.3233/JAD-150113

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S151-S159, 2015

Authors: Koppara, Alexander | Frommann, Ingo | Polcher, Alexandra | Parra, Mario A. | Maier, Wolfgang | Jessen, Frank | Klockgether, Thomas | Wagner, Michael

Article Type: Research Article

Abstract: Background: Feature binding is a sensitive and specific cognitive marker for Alzheimer’s disease (AD). Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are clinical categories associated with an increased risk for AD. Objective: To investigate whether the SCD and MCI group are impaired with regard to feature binding. Methods: The feature binding test was administered to memory clinic patients with either SCD (n  = 19, mean MMSE: 29.2) or with MCI (n  = 23, mean MMSE: 26.5), and to a group of healthy controls (HC, n  = 23, mean MMSE: 29.0). Participants were assessed with the CERAD …Plus neuropsychological test battery. Cognitive performance of the three groups was compared by ANCOVA with age, gender and education as covariates and planned contrasts. Results: Groups differed in the binding condition. Planned contrasts showed significant differences in adjusted means between HC and SCD (p  = 0.003), as well as between HC and MCI (p  <  0.0001). Discussion: The feature binding task detects subtle cognitive impairments in participants with SCD, who are unimpaired in traditional neuropsychological testing. This corroborates the use of feature binding tests in preclinical AD studies and suggests that specific cognitive deficits can be found in SCD. Future studies incorporating AD biomarkers and longitudinal follow-up are needed to further establish the clinical utility of feature binding. Show more

Keywords: Alzheimer’s disease, early detection, feature binding, mild cognitive impairment, subjective cognitive decline

DOI: 10.3233/JAD-150105

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S161-S170, 2015

Authors: Lista, Simone | Molinuevo, Jose L. | Cavedo, Enrica | Rami, Lorena | Amouyel, Philippe | Teipel, Stefan J. | Garaci, Francesco | Toschi, Nicola | Habert, Marie-Odile | Blennow, Kaj | Zetterberg, Henrik | O’Bryant, Sid E. | Johnson, Leigh | Galluzzi, Samantha | Bokde, Arun L.W. | Broich, Karl | Herholz, Karl | Bakardjian, Hovagim | Dubois, Bruno | Jessen, Frank | Carrillo, Maria C. | Aisen, Paul S. | Hampel, Harald

Article Type: Review Article

Abstract: There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer’s disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the …cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ 4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials. Show more

Keywords: Alzheimer’s disease, biological markers, blood-based biomarkers, cerebrospinal fluid biomarkers, clinical trials, functional MRI markers, molecular imaging markers, preclinical Alzheimer’s disease, structural MRI markers, subjective cognitive decline

DOI: 10.3233/JAD-150202

Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S171-S191, 2015