Journal of Alzheimer's Disease Reports - Volume 6, issue 1

Authors: Avey, Jaedon P. | Schaefer, Krista R. | Noonan, Carolyn J. | Muller, Clemma J. | Mosley, Michael | Galvin, James E.

Article Type: Research Article

Abstract: Background: Alaska Native and American Indian (AN/AI) people represent a rapidly aging population with disproportionate burdens of Alzheimer’s disease and related dementias (ADRD) risk factors. Objective: To characterize healthcare service use patterns and mortality in the years following ADRD diagnosis for patients in an Alaska Native Tribal health system. Methods: The study sample included all AN/AI patients aged 55 or older with an ADRD diagnosis who were seen between 2012–2018 (n  = 407). We used cluster analysis to identify distinct patterns of healthcare use for primary care, emergency and urgent care, inpatient hospital stays, and selected specialty …care. We compared demographic and clinical factors between clusters and used regression to compare mortality. Results: We identified five clusters of healthcare service use patterns after ADRD diagnosis: 1) people who use a low amount of all services (n  = 107), 2) people who use a high amount of all services (n  = 60), 3) people who use a high amount of primary and specialty care (n  = 105), 4) people who use a high amount of specialty care (n  = 65), and 5) people who use a high amount of emergency and urgent care (n  = 70). The cluster with the highest use had the greatest proportion of comorbidities and had a 2.3-fold increased risk of mortality compared to the cluster with the lowest healthcare service use. Conclusion: Results indicate that those receiving the most services had the greatest healthcare-related needs and increased mortality. Future research could isolate factors that predict service use following ADRD diagnosis and identify other differential health risks. Show more

Keywords: Alaska Native, Alzheimer’s disease, American Indian, cluster analysis, delivery of healthcare, dementia, geriatrics, health services

DOI: 10.3233/ADR-210062

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 401-410, 2022

Authors: Zuroff, Leah | Wisse, Laura EM | Glenn, Trevor | Xie, Sharon X. | Nasrallah, Ilya M. | Habes, Mohamad | Dubroff, Jacob | de Flores, Robin | Xie, Long | Yushkevich, Paul | Doshi, Jimit | Davatsikos, Christos | Shaw, Leslie M. | Tropea, Thomas F. | Chen-Plotkin, Alice S. | Wolk, David A | Das, Sandhitsu | Mechanic-Hamilton, Dawn

Article Type: Research Article

Abstract: Background: Episodic memory decline is a hallmark of Alzheimer’s disease (AD). Subjective memory complaints (SMCs) may represent one of the earliest signs of impending cognitive decline. The degree to which self- or partner-reported SMCs predict cognitive change remains unclear. Objective: We aimed to evaluate the relationship between self- and partner-reported SMCs, objective cognitive performance, AD biomarkers, and risk of future decline in a well-characterized longitudinal memory center cohort. We also evaluated whether study partner characteristics influence reports of SMCs. Methods: 758 participants and 690 study partners were recruited from the Penn Alzheimer’s Disease Research Center Clinical …Core. Participants included those with Normal Cognition, Mild Cognitive Impairment, and AD. SMCs were measured using the Prospective and Retrospective Memory Questionnaire (PRMQ), and were evaluated for their association with cognition, genetic, plasma, and neuroimaging biomarkers of AD, cognitive and functional decline, and diagnostic progression over an average of four years. Results: We found that partner-reported SMCs were more consistent with cognitive test performance and increasing symptom severity than self-reported SMCs. Partner-reported SMCs showed stronger correlations with AD-associated brain atrophy, plasma biomarkers of neurodegeneration, and longitudinal cognitive and functional decline. A 10-point increase on baseline PRMQ increased the annual risk of diagnostic progression by approximately 70%. Study partner demographics and relationship to participants influenced reports of SMCs in AD participants only. Conclusion: Partner-reported SMCs, using the PRMQ, have a stronger relationship with the neuroanatomic and cognitive changes associated with AD than patient-reported SMCs. Further work is needed to evaluate whether SMCs could be used to screen for future decline. Show more

Keywords: Alzheimer’s disease, brain atrophy, memory decline, mild cognitive impairment, proxy, self-report, subjective memory complaints

DOI: 10.3233/ADR-220013

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 411-430, 2022

Authors: Gallucci, Maurizio | Grassivaro, Francesca | Da Ronch, Chiara | Fiore, Vittorio | Bonifati, Domenico Marco | Bendini, Matteo | Zanusso, Gianluigi | Bonanni, Laura

Article Type: Research Article

Abstract: Background: An 82-year-old right-handed man, a retired teacher, reported the occurrence, three years earlier, of difficulties in moving his left arm and foot, tremor in his left hand, and gestures of the left upper limb that appeared to be independent of the patient’s will. Objective: We describe an unusual case of corticobasal syndrome (CBS) showing disease-associated biomarkers of dementia with Lewy bodies (DLB). Methods: Clinical, neuropsychological, imaging, and biomarker evaluations were conducted, including tau and amyloid-β levels in the cerebrospinal fluid (CSF) and a RT-QuIC assay for α-synuclein both in the CSF and olfactory mucosa (OM), …as well as a QEEG assessment. Results: The patient presented resting tremor, mild extrapyramidal hypertonus, mild bradykinesia on the left side, and severe apraxia on the left upper limb. Brain MRI showed a diffuse right hemisphere atrophy which was prominent in the posterior parietal and temporal cortices, and moderate in the frontal cortex and the precuneus area. 18 F-FDG PET imaging showed reduced glucose metabolism in the right lateral parietal, temporal, and frontal cortices with involvement of the right precuneus. The putamen did not appear to be pathological at DaTQUANT. Neuropsychological tests showed memory and visual-perceptual deficits. CSF tau and amyloid measurements did not show clear pathological values. RT-QuIC for α-synuclein in CSF and OM samples were positive. The QEEG analysis showed a pre-alpha dominant frequency in posterior derivations, typical of early stages of DLB. Conclusion: Although in the present patient the clinical diagnosis was of probable CBS, unexpectedly positive biomarkers for DLB suggested the co-presence of multiple pathologies. Show more

Keywords: α-synuclein, corticobasal syndrome, dementia with Lewy bodies, 18F-FDG-PET, magnetic resonance, neurodegenerative diseases, quantitative electroencephalography, real-time quaking-induced conversion, tauopathy, TREDEM

DOI: 10.3233/ADR-220026

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 431-442, 2022

Authors: Dai, Jiahui | Ports, Kayleen Deanna | Corrada, Maria M. | Odegaard, Andrew O. | O’Connell, Joan | Jiang, Luohua

Article Type: Research Article

Abstract: Background: When studying drug effects using observational data, time-related biases may exist and result in spurious associations. Numerous observational studies have investigated metformin and dementia risk, but have reported inconsistent findings, some of which might be caused by unaddressed time-related biases. Immortal time bias biases the results toward a “protective” effect, whereas time-lag and time-window biases can lead to either a “detrimental” or “protective” effect. Objective: To conduct a systematic review examining time-related biases in the literature on metformin and dementia. Methods: The electronic databases PubMed, Web of Science, and ProQuest were searched for the terms …“Metformin” AND (“dementia” OR “Alzheimer’s Disease” OR “cognitive impairment"). These databases were searched from inception through 09/24/2021. Only English language articles and human research were eligible. Results: Seventeen studies were identified: thirteen cohort studies, two case-control studies, and two nested case-control studies. Eleven (64.7%) studies reported a reduced risk of dementia associated with metformin use; two (11.8%) suggested metformin increased dementia risk, while four (23.5%) concluded no significant associations. Eight (61.5%) of thirteen cohort studies had immortal time bias or did not clearly address it. Fifteen (88.2%) of seventeen reviewed studies had time-lag bias or did not clearly address it. Two (50.0%) of four case-control studies did not explicitly address time-window bias. The studies that addressed most biases concluded no associations between metformin and dementia risk. Conclusion: None of the reviewed studies clearly addressed relevant time-related biases, illustrating time-related biases are common in observational studies investigating the impact of anti-diabetic medications on dementia risk. Show more

Keywords: Bias, case-control studies, cohort studies, dementia, metformin

DOI: 10.3233/ADR-220002

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 443-459, 2022

Authors: Sobregrau, Pau | Peri, Josep M. | Sánchez del Valle, Raquel | Molinuevo, Jose L. | Barra, Bernardo | Pintor, Luís

Article Type: Research Article

Abstract: Background: Predictive genetic tests are presently effective over several medical conditions, increasing the demand among patients and healthy individuals. Considering the psychological burden suspected familial dementia may carry on individuals, assessing personality, coping strategies, and mental health could aid clinicians in findings the appropriate time for delivering genetic test results and predict compliance regarding genetic counseling and expectations towards the genetic condition depending on the outcome. Objective: To describe the psychiatric, psychological, and coping characteristics of a sample of Spanish individuals at risk of familial dementia before genetic test results were given. Methods: We included 54 …first degree relatives of patients diagnosed with Alzheimer’s disease, lobar frontotemporal degeneration, or prion diseases. The NEO-FFI-R, COPE, and HADS tests evaluated personality, coping strategies, and psychological distress, respectively. Results: Anxiety and depression were below the cut-off point for mild severity. Conscientiousness and Agreeableness were the most preponderant personality factors, while Neuroticism was the least. Positive reinterpretation and Acceptance were the most frequent coping strategies, and Denial and Alcohol and drug use were the least used. Ongoing medical pathologies increased depression, while psychiatric disorders worsened psychological distress. Conclusion: Contrary to our expectations, PICOGEN candidates showed psychological distress and personality traits within normative ranges, and the use of problem-focused coping strategies prevailed over avoidance coping strategies. Nevertheless, clinicians should pay particular attention to individuals attending genetic counseling who are women, aged, and present an ongoing psychiatric disorder and psychiatric history at inclusion to ensure their mental health and adherence throughout the process. Show more

Keywords: Alzheimer’s disease, dementia, frontotemporal lobar degeneration, genetic counseling, genetic testing, neurodegenerative diseases,, prion diseases, psychiatry, psychology

DOI: 10.3233/ADR-210067

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 461-478, 2022

Authors: Butts, Alissa M. | Machulda, Mary M. | Martin, Peter | Przybelski, Scott A. | Duffy, Joseph R. | Graff-Radford, Jonathan | Knopman, David S. | Petersen, Ronald C. | Jack Jr., Clifford R. | Lowe, Val J. | Josephs, Keith A. | Whitwell, Jennifer L.

Article Type: Research Article

Abstract: Background: The hippocampus and temporal lobe are atrophic in typical amnestic Alzheimer’s disease (tAD) and are used as imaging biomarkers in treatment trials. However, a better understanding of how temporal structures differ across atypical AD phenotypes and relate to cognition is needed. Objective: Our goal was to compare temporal lobe regions between tAD and two atypical AD phenotypes (logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA)), and assess cognitive associations. Methods: We age and gender-matched 77 tAD participants to 50 LPA and 27 PCA participants, all of which were amyloid-positive. We used linear mixed-effects models …to compare FreeSurfer-derived hippocampal volumes and cortical thickness of entorhinal, inferior and middle temporal, and fusiform gyri, and to assess relationships between imaging and memory, naming, and visuospatial function across and within AD phenotype. Results: Hippocampal volume and entorhinal thickness were smaller bilaterally in tAD than LPA and PCA. PCA showed greater right inferior temporal and bilateral fusiform thinning and LPA showed greater left middle and inferior temporal and left fusiform thinning. Atypical AD phenotypes differed with greater right hemisphere thinning in PCA and greater left hemisphere thinning in LPA. Verbal and visual memory related most strongly to hippocampal volume; naming related to left temporal thickness; and visuospatial related to bilateral fusiform thickness. Fewer associations remained when examined within AD group. Conclusion: Atypical AD phenotypes are associated with greater thinning of lateral temporal structures, with relative sparing of medial temporal lobe, compared to tAD. These findings may have implications for future clinical trials in AD. Show more

Keywords: Alzheimer’s disease, atypical Alzheimer’s disease, cortical thickness, hippocampal volumes, logopenic progressive aphasia, memory, neuropsychological functioning, object naming, posterior cortical atrophy, visual spatial

DOI: 10.3233/ADR-220010

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 479-491, 2022

Authors: Franczak, Stephanie | Pommy, Jessica | Minor, Greta | Zolliecoffer, Chandler | Bhalla, Manav | Agarwal, Mohit | Nencka, Andrew | Wang, Yang | Klein, Andrew | O’Neill, Darren | Henry, Jude | Umfleet, Glass

Article Type: Research Article

Abstract: Background: There are now clinically available automated MRI analysis software programs that compare brain volumes of patients to a normative sample and provide z -score data for various brain regions. These programs have yet to be validated in primary progressive aphasia (PPA). Objective: To address this gap in the literature, we examined Neuroreader™ z -scores in PPA, relative to visual MRI assessment. We predicted that Neuroreader™ 1) would be more sensitive for detecting left > right atrophy in the cortical lobar regions in logopenic variant PPA clinical phenotype (lvPPA), and 2) would distinguish lvPPA (n  = 11) from amnestic …mild cognitive impairment (aMCI; n  = 12). Methods: lvPPA or aMCI patients who underwent MRI with Neuroreader™ were included in this study. Two neuroradiologists rated 10 regions. Neuroreader™ lobar z-s cores for those 10 regions, as well as a hippocampal asymmetry metric, were included in analyses. Results: Cohen’s Kappa coefficients were significant in 10 of the 28 computations (k  = 0.351 to 0.593, p ≤0.029). Neuroradiologists agreed 0% of the time that left asymmetry was present across regions. No significant differences emerged between aMCI and lvPPA in Neuroreader™ z -scores across left or right frontal, temporal, or parietal regions (p s > 0.10). There were significantly lower z- scores in the left compared to right for the hippocampus, as well as parietal, occipital, and temporal cortices in lvPPA. Conclusion: Overall, our results indicated moderate to low interrater reliability, and raters never agreed that left asymmetry was present. While lower z -scores in the left hemisphere regions emerged in lvPPA, Neuroreader™ failed to differentiate lvPPA from aMCI. Show more

Keywords: Logopenic variant PPA, magnetic resonance imaging, mild cognitive impairment, neuroreader

DOI: 10.3233/ADR-220036

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 493-501, 2022

Authors: Giannouli, Vaitsa | Tsolaki, Magda

Article Type: Short Communication

Abstract: This study examines the connection between biological factors, social determinants, and behavioral and psychological symptoms of dementia (BPSD) and the estimations of financial capacity made by caregivers of mild AD patients in Greece. Financial capacity estimations negatively correlated with biological sex of the patients (female), but Neuropsychiatric Inventory (NPI) scores were statistically lower for older females. BPSD (measured with NPI) was found to negatively correlate with estimates of financial capacity. The existence of delusions-hallucinations was reported in all males. No correlations were found between financial capacity estimations, actual cognitive and financial capacity performance, and all other included biological and social …characteristics of the patients as well as their caregivers. Show more

Keywords: Behavioral and psychological symptoms of dementia, biological factors, caregivers, financial capacity estimations, social determinants

DOI: 10.3233/ADR-220037

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 503-507, 2022

Authors: Pirani, Alessandro | Nasreddine, Ziad | Neviani, Francesca | Fabbo, Andrea | Rocchi, Marco Bruno | Bertolotti, Marco | Tulipani, Cristina | Galassi, Matteo | Belvederi Murri, Martino | Neri, Mirco

Article Type: Research Article

Abstract: Background: The early detection of neurocognitive disorders, especially when mild, is a key issue of health care systems including the Italian Dementia National Plan. The Mini-Mental State Examination (MMSE), i.e., the reference screening tool for dementia in Italian Memory Clinics, has low sensitivity in detecting mild cognitive impairment (MCI) or mild dementia. Objective: Availability of a 10-minute screening test sensitive to MCI and mild dementia, such as the Montreal Cognitive Assessment (MoCA), is relevant in the field. This study presents initial validity and reliability data for the Italian version of MoCA 7.1 that is being collected as part …of a large ongoing longitudinal study to evaluate the rate of incident MCI and dementia in older adults. Methods: MoCA 7.1 and MMSE were administered to cognitive impaired patients (n  = 469; 214 with MCI, 255 with dementia; mean age: 75.5; 52% females,) and healthy older adults (n  = 123, mean age: 69.7, 64 % females). Results: Test-retest (0.945, p  < 0.001) and inter-rater (0.999, p  < 0.001) reliability of MoCA 7.1, assessed on randomly selected participants with normal cognition, MCI, dementia, were significant. MoCA 7.1 showed adequate sensitivity (95.3%) and specificity (84.5%) in detecting MCI compared to MMSE (sensitivity: 53.8%; specificity: 87.5%). The Area Under the Curve of MoCA 7.1 was significantly greater than that of MMSE (0.963 versus 0.742). MoCA 7.1 showed similar results in detecting both MCI and dementia. Conclusion: MoCA 7.1 is a reliable and useful tool that can aid in the diagnosis of MCI and dementia in the Italian population. Show more

Keywords: Brief cognitive screening test, dementia, early cognitive impairment detection, mild cognitive impairment, Montreal Cognitive Assessment, neurocognitive disorders

DOI: 10.3233/ADR-210053

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 509-520, 2022

Authors: Roe, Catherine M.

Article Type: Review Article

Abstract: Research on how preclinical and early symptomatic Alzheimer’s disease (AD) impacts driving behavior is in its infancy, with several important research areas yet to be explored. This paper identifies research gaps and suggests priorities for driving studies over the next few years among those at the earliest stages of AD. These priorities include how individual differences in demographic and biomarker measures of AD pathology, as well as differences in the in-vehicle and external driving environment, affect driving behavior. Understanding these differences is important to developing future interventions to increase driving safety among those at the earliest stages of AD.

Keywords: biomarkers, driving, early Alzheimer’s disease, mild cognitive impairment, preclinical Alzheimer’s disease

DOI: 10.3233/ADR-220024

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 521-528, 2022