Journal of Alzheimer's Disease - Volume 89, issue 3

Authors: Rogers, Joseph

Article Type: Obituary

DOI: 10.3233/JAD-229010

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 757-758, 2022

Authors: Freberg, Elissa | Taglialatela, Giulio

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) and major depressive disorder (MDD) affect millions worldwide and both cause significant morbidity and mortality. While clinically distinctive, patients with MDD can present with memory dysfunction and patients with AD commonly report symptoms of depression. Additionally, brain pathology in MDD and AD both demonstrate decreased hippocampal volumes, and severe disease is associated with smaller hippocampal volumes in both disorders. Hippocampal neurogenesis occurs daily in healthy individuals, an impaired process in AD and MDD. MDD is thus suggested to be a risk factor for developing AD later in life; moreover, depression onset alongside AD indicates a worse prognosis. …Treatment options that target hippocampal neurogenesis are being evaluated for both diseases, and aerobic exercise has shown promising results. We searched PubMed for relevant review articles published since 2000 encompassing the topics of hippocampal neurogenesis and exercise in relation to depression and AD, including novel clinical trials if they contributed information not in the chosen reviews. While much data indicates that exercise increases hippocampal neurogenesis in both MDD and AD, mood improvement in MDD, mild quality of life and cognitive improvement in AD, and reduced risk of those with MDD developing AD in response to various exercise regimens, this result was not universal. Some data indicated no difference between exercise groups and controls. Further randomized control trials into exercise as an intervention in treating MDD and preventing AD is required. However, exercise is a low-risk, affordable treatment option and is a feasible additive therapy in patients with AD and MDD. Show more

Keywords: Alzheimer’s disease, cognitive dysfunction, depression, exercise, neurogenesis

DOI: 10.3233/JAD-210632

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 759-767, 2022

Authors: Dessy, Alexa | Zhao, Amanda J. | Kyaw, Kay | Vieira, Dorice | Salinas, Joel

Article Type: Systematic Review

Abstract: Background: As the Hispanic/Latino (HL) population grows, so too does the need for HL family caregivers for persons with dementia. HL caregivers tend to have less education, lower health literacy, and lower income, each uniquely compounding burden. Research is needed to appropriately tailor interventions for this population. Objective: A systematic review and meta-analysis was conducted to 1) provide an updated review of non-pharmacologic intervention studies for HL dementia caregivers, 2) characterize promising interventions, and 3) highlight opportunities for future research. Methods: Databases were searched for articles evaluating non-pharmacologic interventions for HL dementia caregivers. Studies were excluded …if target populations did not include HLs or if no intervention was delivered. Data were extracted and random effects meta-analysis was performed on two primary outcomes: caregiver depression and burden. Effect sizes were calculated as pre- and post-intervention standardized mean differences (SMD), and further depression subgroup meta-analysis was performed. Other secondary outcome measures (e.g., perceived social support, caregiver knowledge, anxiety) were evaluated qualitatively. Results: Twenty-three studies were identified. Most included multiple components pertaining to psychosocial support, caregiver education, and community resource facilitation. Many studies were successful in improving caregiver outcomes, though intervention design varied. Meta-analysis revealed minimal to moderate heterogeneity and small effect size in improving depressive symptoms (SMD = –0.31, 95% CI –0.46 to –0.16; I2  = 50.16%) and burden (SMD = –0.28, 95% CI –0.37 to –0.18; I2  = 11.06%). Conclusion: Although intervention components varied, many reported outcome improvements. Future studies may benefit from targeting physical health, addressing sociocultural and economic contexts of caregivers, and leveraging technology. Show more

Keywords: Alzheimer’s disease, caregiver burden, caregivers, dementia, Hispanic/Latino, intervention, minority health

DOI: 10.3233/JAD-220005

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 769-788, 2022

Authors: Godbee, Kali | Guccione, Lisa | Palmer, Victoria J. | Gunn, Jane | Lautenschlager, Nicola | Francis, Jill J.

Article Type: Research Article

Abstract: Background: Primary care practitioners are being called upon to work with their patients to reduce dementia risk. However, it is unclear who should do what with whom, when, and under what circumstances. Objective: This scoping review aimed to identify clinical guidelines for dementia risk reduction (DRR) in primary care settings, synthesize the guidelines into actionable behaviors, and appraise the guidelines for specificity. Methods: Terms related to “dementia”, “guidelines”, and “risk reduction” were entered into two academic databases and two web search engines. Guidelines were included if they referred specifically to clinical practices for healthcare professionals for …primary prevention of dementia. Included guidelines were analyzed using a directed content analysis method, underpinned by the Action-Actor-Context-Target-Time framework for specifying behavior. Results: Eighteen guidelines were included in the analysis. Together, the guidelines recommended six distinct clusters of actions for DRR. These were to 1) invite patients to discuss DRR, 2) identify patients with risk factors for dementia, 3) discuss DRR, 4) manage dementia risk factors, 5) signpost to additional support, and 6) follow up. Guidelines recommended various actors, contexts, targets, and times for performing these actions. Together, guidelines lacked specificity and were at times contradictory. Conclusion: Currently available guidelines allow various approaches to promoting DRR in primary care. Primary care teams are advised to draw on the results of the review to decide which actions to undertake and the locally appropriate actors, contexts, targets, and times for these actions. Documenting these decisions in more specific, local guidelines for promoting DRR should facilitate implementation. Show more

DOI: 10.3233/JAD-220382

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 789-802, 2022

Authors: Woodward, Michael | Brodaty, Henry | McCabe, Maree | Masters, Colin L. | Naismith, Sharon L. | Morris, Philip | Rowe, Christopher C. | Walker, Peter | Yates, Mark

Article Type: Editorial

Abstract: Prior to the usual clinical symptoms of dementia, there can be subtle changes in cognitive function that differ from the normal age-related cognitive decline, which has been termed mild cognitive impairment (MCI). The increase in the numbers of individuals with possible MCI presenting to health care professionals, notably, General Practitioners (GPs), is going to rise dramatically in the coming years. With ever increasing demands on GPs, it is therefore timely to provide information that can be accessed by health care professionals to assist them in making appropriate diagnoses and to provide the most relevant, evidence-based treatment options. We have provided …a comprehensive list of recommendations that aim to address key aspects of MCI in primary care. Specifically, these relate to detection and diagnosis; sharing the diagnosis, monitoring, and follow up; practical interventions to potentially delay progression; and personalizing care—planning, engagement, and patient motivation for the long term. Show more

Keywords: Assessment, diagnosis, guidelines, management, mild cognitive impairment, primary care

DOI: 10.3233/JAD-220288

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 803-809, 2022

Authors: Serra, Laura | Giancaterino, Giulia | Giulietti, Giovanni | Petrosini, Laura | Di Domenico, Carlotta | Marra, Camillo | Caltagirone, Carlo | Bassi, Andrea | Cercignani, Mara | Bozzali, Marco

Article Type: Research Article

Abstract: Background: Cognitive reserve (CR) explains the individual resilience to neurodegeneration. Objective: The present study investigated the effect of CR in modulating brain cortical architecture. Methods: 278 individuals [110 Alzheimer’s disease (AD), 104 amnestic mild cognitive impairment (aMCI) due to AD, 64 healthy subjects (HS)] underwent a neuropsychological evaluation and 3T-MRI. Cortical thickness (CTh) and fractal dimension (FD) were assessed. Years of formal education were used as an index of CR by which participants were divided into high and low CR (HCR and LCR ). Within-group differences in cortical architecture were assessed as a function of …CR. Associations between cognitive scores and cortical measures were also evaluated. Results: aMCI-HCR compared to aMCI-LCR patients showed significant decrease of CTh in the right temporal and in the left prefrontal lobe. Moreover, they showed increased FD in the right temporal and in the left temporo-parietal lobes. Patients with AD-HCR showed reduced CTh in several brain areas and reduced FD in the left temporal cortices when compared with AD-LCR subjects. HS-HCR showed a significant increase of CTh in prefrontal areas bilaterally, and in the right parieto-occipital cortices. Finally, aMCI-HCR showed significant positive associations between brain measures and memory and executive performance. Conclusion: CR modulates the cortical architecture at pre-dementia stage only. Indeed, only patients with aMCI showed both atrophy (likely due to neurodegeneration) alongside richer brain folding (likely due to reserve mechanisms) in temporo-parietal areas. This opposite trend was not observed in AD and HS. Our data confirm the existence of a limited time-window for CR modulation at the aMCI stage. Show more

Keywords: Alzheimer’s disease, cognitive reserve, cortical thickness, fractal dimension, mild cognitive impairment

DOI: 10.3233/JAD-220377

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 811-824, 2022

Authors: Soares, Jelena Zugic | Valeur, Jørgen | Šaltytė Benth, Jūratė | Knapskog, Anne-Brita | Selbæk, Geir | Bogdanovic, Nenad | Pettersen, Renate

Article Type: Research Article

Abstract: Background: Several studies have examined association between vitamin D levels in serum and cognition, but little is known of vitamin D levels in cerebrospinal fluid (CSF) and association with Alzheimer’s disease (AD). Objective: In this cross-sectional, explorative study we investigated possible associations of vitamin D in CSF with biomarkers for AD, amyloid-β, tau protein/phosphorylated tau protein in CSF, and with the cytokines IL-6, IL-8, and TNF-α in CSF in patients with cognitive impairment and cognitively healthy controls. Methods: We included 100 outpatients ≥65 years referred for assessment of cognitive impairment and 76 age- and sex-matched cognitively …healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D), amyloid-β, tau protein and phosphorylated tau protein, as well as IL-6, IL-8, and TNF-α, were analyzed in CSF in both groups. Results: Higher levels of 25(OH)D in CSF in all groups together were associated with lower levels of tau protein (p  = 0.01) and phosphorylated tau protein (p  = 0.005). We found no association between 25(OH)D levels in CSF and pathological levels of amyloid-β in CSF nor levels of IL-6 or TNF-α in CSF. Higher levels of 25(OH)D in CSF were associated with higher levels of IL-8 in CSF (p  = 0.002). However, vitamin D explained only 6% of variance in IL-8. There was no significant difference between the patient groups and the control group regarding the association between 25(OH)D in CSF and any of the three cytokines in CSF. Conclusion: Participants with higher CSF levels of 25(OH)D exhibited reduced CSF levels of tau protein and phosphorylated tau protein. Show more

Keywords: Alzheimer’s disease, blood-brain barrier, cerebrospinal fluid, cognitive function, cytokines, dementia, tau protein, vitamin D

DOI: 10.3233/JAD-220407

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 825-834, 2022

Authors: Matsuzaki Tada, Asuka | Hamezah, Hamizah Shahirah | Pahrudin Arrozi, Aslina | Abu Bakar, Zulzikry Hafiz | Yanagisawa, Daijiro | Tooyama, Ikuo

Article Type: Research Article

Abstract: Background: Tripeptide Met-Lys-Pro (MKP), a component of casein hydrolysates, has effective angiotensin-converting enzyme (ACE) inhibitory activity. Brain angiotensin II enzyme activates the NADPH oxidase complex via angiotensin II receptor type 1 (AT1) and enhances oxidative stress injury. ACE inhibitors improved cognitive function in Alzheimer’s disease (AD) mouse models and previous clinical trials. Thus, although undetermined, MKP may be effective against pathological amyloid-β (Aβ) accumulation-induced cognitive impairment. Objective: The current study aimed to investigate the potential of MKP as a pharmaceutical against AD by examining MKP’s effect on cognitive function and molecular changes in the brain using double transgenic …(APP/PS1) mice. Methods: Experimental procedures were conducted in APP/PS1 mice (n  = 38) with a C57BL/6 background. A novel object recognition test was used to evaluate recognition memory. ELISA was used to measure insoluble Aβ40 , Aβ42 , and TNF-α levels in brain tissue. Immunohistochemical analysis allowed the assessment of glial cell activation in MKP-treated APP/PS1 mice. Results: The novel object recognition test revealed that MKP-treated APP/PS1 mice showed significant improvement in recognition memory. ELISA of brain tissue showed that MKP significantly reduced insoluble Aβ40 , Aβ42 , and TNF-α levels. Immunohistochemical analysis indicated the suppression of the marker for microglia and reactive astrocytes in MKP-treated APP/PS1 mice. Conclusion: Based on these results, we consider that MKP could ameliorate pathological Aβ accumulation-induced cognitive impairment in APP/PS1 mice. Furthermore, our findings suggest that MKP potentially contributes to preventing cognitive decline in AD. Show more

Keywords: Alzheimer’s disease, APP/PS1 mice, dementia, Met-Lys-Pro, MKP, peptide

DOI: 10.3233/JAD-220192

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 835-848, 2022

Authors: Fingerhut, Hannah | Gozdas, Elveda | Hosseini, S.M. Hadi

Article Type: Research Article

Abstract: Background: Cognitive reserve (CR) has been postulated to contribute to the variation observed between neuropathology and clinical outcomes in Alzheimer’s disease (AD). Objective: We investigated the effect of an education-occupation derived CR proxy on biological properties of white matter tracts in patients with amnestic mild cognitive impairment (aMCI) and healthy elders (HC). Methods: Educational attainment and occupational complexity ratings (complexity with data, people, and things) from thirty-five patients with aMCI and twenty-eight HC were used to generate composite CR scores. Quantitative magnetic resonance imaging (qMRI) and multi-shell diffusion MRI were used to extract macromolecular tissue …volume (MTV) across major white matter tracts. Results: We observed significant differences in the association between CR and white matter tract MTV in aMCI versus HC when age, gender, intracranial volume, and memory ability were held constant. Particularly, in aMCI, higher CR was associated with worse tract pathology (lower MTV) in the left and right dorsal cingulum, callosum forceps major, right inferior fronto-occipital fasciculus, and right superior longitudinal fasciculus (SLF) tracts. Conversely higher CR was associated with higher MTV in the right parahippocampal cingulum and left SLF in HC. Conclusion: Our results support compensatory CR mechanisms in aMCI and neuroprotective mechanisms in HC and suggest differential roles for CR on white matter macromolecular properties in healthy elders versus prodromal AD patients. Show more

Keywords: Alzheimer’s disease, brain reserve, cognitive reserve, mild cognitive impairment, quantitative magnetic resonance imaging (qMRI), white matter tracts

DOI: 10.3233/JAD-220197

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 849-863, 2022

Authors: Torkpoor, Rozita | Frolich, Kristin | Nielsen, T. Rune | Londos, Elisabet

Article Type: Research Article

Abstract: Background: The number of people with a migration background and dementia is increasing in Europe. All patients with suspected dementia have the right to an appropriate cognitive assessment and correct diagnosis for optimal treatment and support. Rowland Universal Dementia Assessment Scale (RUDAS) cognitive screening instrument is less affected by language, culture, and educational background, and adapted for use in multicultural populations. Objective: To compare the diagnostic accuracy of RUDAS-S to the Swedish version of Mini-Mental State Examination (MMSE-SR) for detecting dementia in a multicultural group of outpatients in Swedish memory clinics. Methods: We tested 123 outpatients …(36 nonnative Swedish), in 4 memory clinics in Southern Sweden with RUDAS-S to supplement the usual cognitive assessment. Results: RUDAS-S had moderate to good diagnostic performance for detecting dementia in a multicultural population in Sweden, with an area under the receiver operating characteristic curve (AUC) of 0.81. At a cutoff score <25 its sensitivity was 0.92, specificity 0.60, and accuracy 76%. The AUC for the MMSE-SR was 0.79. At a cutoff score <23 its sensitivity was 0.65, specificity 0.81, and accuracy 73%. Conclusion: RUDAS-S is at least as accurate as MMSE-SR for detecting dementia in memory clinics in Sweden and can be used for all patients undergoing a cognitive assessment, irrespective of their cultural, language, and educational background. However, there is a need for other cross-cultural cognitive tests to complement RUDAS-S to extend cognitive examination. Show more

Keywords: Assessment, cognition, cross-cultural screening test, dementia, ethnic minority, immigrant, Mini-Mental State Examination, Rowland Universal Dementia Assessment Scale

DOI: 10.3233/JAD-220233

Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 865-876, 2022