Dementia Around the World and the Latin America and Mexican ScenariosBrito-Aguilar, Rafael
doi: 10.3233/JAD-190177pmid: 31322565
Dementia has become a major public health concern around the world. Dementia risk factors are significantly different among countries. The number of new cases of dementia anticipated each year worldwide is almost 7.7 million, one new case every four seconds. There are 3.6 million (46%) new cases per year in Asia, 2.3 million (31%) in Europe, 1.2 million (16%) in the Americas, and 0.5 million (7%) in Africa. Latin American and Caribbean low and middle-income countries are at high risk. Air pollution is an important risk modifiable factor for dementia across the world, and the recent report of the Alzheimer’s disease continuum in children and young adults residing in Metropolitan Mexico City along with the presence of cognitive impairment in 55% of the young adult population residing in Mexican cities with fine particulate matter concentrations above the current USEPA annual standard of 12 μg/m3 makes this a severe public health problem in progress. It is imperative to keep generating epidemiological data on dementia worldwide and their relationship with air pollutants to improve the strategies to face all the challenges associated with dementia and Alzheimer’s disease in particular. Alzheimer’s disease is a fatal disease, we have no cure, and we ought to invest in protecting our citizens by intervening in modifiable environmental factors.
Dementia Around the World and the Latin America and Mexican ScenariosBrito-Aguilar, Rafael
doi: 10.3233/jad-190177pmid: 31322565
Dementia has become a major public health concern around the world. Dementia risk factors are significantly different among countries. The number of new cases of dementia anticipated each year worldwide is almost 7.7 million, one new case every four seconds. There are 3.6 million (46%) new cases per year in Asia, 2.3 million (31%) in Europe, 1.2 million (16%) in the Americas, and 0.5 million (7%) in Africa. Latin American and Caribbean low and middle-income countries are at high risk. Air pollution is an important risk modifiable factor for dementia across the world, and the recent report of the Alzheimer’s disease continuum in children and young adults residing in Metropolitan Mexico City along with the presence of cognitive impairment in 55% of the young adult population residing in Mexican cities with fine particulate matter concentrations above the current USEPA annual standard of 12 μg/m3 makes this a severe public health problem in progress. It is imperative to keep generating epidemiological data on dementia worldwide and their relationship with air pollutants to improve the strategies to face all the challenges associated with dementia and Alzheimer’s disease in particular. Alzheimer’s disease is a fatal disease, we have no cure, and we ought to invest in protecting our citizens by intervening in modifiable environmental factors.
Cerebrospinal Fluid Amyloid-β Subtypes in Confirmed Frontotemporal Lobar Degeneration Cases: A Pilot StudyVerwey, Nicolaas A.; Teunissen, Charlotte E.; Hoozemans, Jeroen J.M.; Rozemuller, Annemieke J.M.; Scheltens, Philip; Pijnenburg, Yolande A.L.
doi: 10.3233/JAD-190344pmid: 31356209
To investigate amyloid-β (Aβ) in frontotemporal dementia (FTD), cerebrospinal fluid (CSF) Aβ38, Aβ40, and Aβ42 in frontotemporal lobar degeneration (FTLD; N = 18 genetically and/or pathologically confirmed and N = 8 FTD with concomitant amyotrophic lateral sclerosis) were compared with Alzheimer’s disease (AD; pathological or Pittsburgh-compound-B Positron-emission-tomography (PIB-PET) positive; N = 25) and controls (N = 24). For all the Aβ subtypes, group difference was seen and post-hoc analysis revealed lower levels in FTLD compared to controls (p≤0.05). Aβ42/40 ratio showed no difference between FTLD and controls; however, a difference was seen between AD versus FTLD (p < 0.01). This is an intriguing finding, suggesting a possible role of Aβ in FTLD pathogenesis.
Cerebrospinal Fluid Amyloid-β Subtypes in Confirmed Frontotemporal Lobar Degeneration Cases: A Pilot StudyVerwey, Nicolaas A.; Teunissen, Charlotte E.; Hoozemans, Jeroen J.M.; Rozemuller, Annemieke J.M.; Scheltens, Philip; Pijnenburg, Yolande A.L.
doi: 10.3233/jad-190344pmid: 31356209
To investigate amyloid-β (Aβ) in frontotemporal dementia (FTD), cerebrospinal fluid (CSF) Aβ38, Aβ40, and Aβ42 in frontotemporal lobar degeneration (FTLD; N = 18 genetically and/or pathologically confirmed and N = 8 FTD with concomitant amyotrophic lateral sclerosis) were compared with Alzheimer’s disease (AD; pathological or Pittsburgh-compound-B Positron-emission-tomography (PIB-PET) positive; N = 25) and controls (N = 24). For all the Aβ subtypes, group difference was seen and post-hoc analysis revealed lower levels in FTLD compared to controls (p≤0.05). Aβ42/40 ratio showed no difference between FTLD and controls; however, a difference was seen between AD versus FTLD (p < 0.01). This is an intriguing finding, suggesting a possible role of Aβ in FTLD pathogenesis.
24S-Hydroxycholesterol Is Associated with Agitation Severity in Patients with Moderate-to-Severe Alzheimer’s Disease: Analyses from a Clinical Trial with NabiloneRuthirakuhan, Myuri; Herrmann, Nathan; Andreazza, Ana C.; Verhoeff, Nicolaas Paul L.G.; Gallagher, Damien; Black, Sandra E.; Kiss, Alex; Lanctôt, Krista L.
doi: 10.3233/JAD-190202pmid: 31322567
Background:Agitation is a prevalent and difficult-to-treat symptom of Alzheimer’s disease (AD). The endocannabinoid system (ECS) has been a target of interest for the treatment of agitation. However, ECS signaling may interact with AD-related changes in brain cholesterol metabolism. Elevated brain cholesterol, reflected by reduced serum 24-S-hydroxycholesterol (24S-OHC), is associated with reduced membrane fluidity, preventing ligand binding to cannabinoid receptor 1.Objective:To assess whether 24S-OHC was associated with agitation severity and response to nabilone.Methods:24S-OHC was collected from AD patients enrolled in a clinical trial on nabilone at the start and end of each phase. This allowed for the cross-sectional and longitudinal investigation between 24S-OHC and agitation (Cohen Mansfield Agitation Inventory, CMAI). Post-hoc analyses included adjustments for baseline standardized Mini-Mental Status Exam (sMMSE), and analyses with CMAI subtotals consistent with the International Psychogeriatric Association (IPA) definition for agitation (physical aggression and nonaggression, and verbal aggression).Results:24S-OHC was not associated with CMAI scores cross-sectionally or longitudinally, before and after adjusting for baseline sMMSE. However, 24S-OHC was associated with greater CMAI IPA scores at baseline (F(1,36) = 4.95, p = 0.03). In the placebo phase only, lower 24S-OHC at baseline was associated with increases in CMAI IPA scores (b = –35.2, 95% CI –65.6 to –5.0, p = 0.02), and decreases in 24S-OHC were associated with increases in CMAI IPA scores (b = –20.94, 95% CI –57.9 to –4.01, p = 0.03).Conclusion:24S-OHC was associated with agitation severity cross-sectionally, and longitudinally in patients with AD. However, 24S-OHC did not predict treatment response, and does not change over time with nabilone.
24S-Hydroxycholesterol Is Associated with Agitation Severity in Patients with Moderate-to-Severe Alzheimer’s Disease: Analyses from a Clinical Trial with NabiloneRuthirakuhan, Myuri; Herrmann, Nathan; Andreazza, Ana C.; Verhoeff, Nicolaas Paul L.G.; Gallagher, Damien; Black, Sandra E.; Kiss, Alex; Lanctôt, Krista L.
doi: 10.3233/jad-190202pmid: 31322567
Background:Agitation is a prevalent and difficult-to-treat symptom of Alzheimer’s disease (AD). The endocannabinoid system (ECS) has been a target of interest for the treatment of agitation. However, ECS signaling may interact with AD-related changes in brain cholesterol metabolism. Elevated brain cholesterol, reflected by reduced serum 24-S-hydroxycholesterol (24S-OHC), is associated with reduced membrane fluidity, preventing ligand binding to cannabinoid receptor 1.Objective:To assess whether 24S-OHC was associated with agitation severity and response to nabilone.Methods:24S-OHC was collected from AD patients enrolled in a clinical trial on nabilone at the start and end of each phase. This allowed for the cross-sectional and longitudinal investigation between 24S-OHC and agitation (Cohen Mansfield Agitation Inventory, CMAI). Post-hoc analyses included adjustments for baseline standardized Mini-Mental Status Exam (sMMSE), and analyses with CMAI subtotals consistent with the International Psychogeriatric Association (IPA) definition for agitation (physical aggression and nonaggression, and verbal aggression).Results:24S-OHC was not associated with CMAI scores cross-sectionally or longitudinally, before and after adjusting for baseline sMMSE. However, 24S-OHC was associated with greater CMAI IPA scores at baseline (F(1,36) = 4.95, p = 0.03). In the placebo phase only, lower 24S-OHC at baseline was associated with increases in CMAI IPA scores (b = –35.2, 95% CI –65.6 to –5.0, p = 0.02), and decreases in 24S-OHC were associated with increases in CMAI IPA scores (b = –20.94, 95% CI –57.9 to –4.01, p = 0.03).Conclusion:24S-OHC was associated with agitation severity cross-sectionally, and longitudinally in patients with AD. However, 24S-OHC did not predict treatment response, and does not change over time with nabilone.