ABSTRACT
To identify knowledge gaps regarding new-onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre-dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late-onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitive decline and dementia. This scoping review of agitation and impulsivity pre-dementia syndromes summarizes the current biomedical literature in terms of epidemiology, diagnosis and measurement, neurobiology, neuroimaging, biomarkers, course and prognosis, treatment, and ongoing clinical trials. Validations for pre-dementia scales such as the MBI Checklist, and incorporation into longitudinal and intervention trials, are needed to better understand impulse dyscontrol as a risk factor for mild cognitive impairment and dementia.
ABSTRACT
BACKGROUND: Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. OBJECTIVE: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). METHODS: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. RESULTS: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. CONCLUSIONS: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.
ANTECEDENTES: El deterioro de la función renal depende de la edad y los factores vasculares. La literatura sobre los efectos de fármacos antihipertensivos mediada genéticamente en la función renal es pobre. OBJETIVO: Estimar las variaciones de urea y creatinina a través del análisis farmacogenético de los efectos antihipertensivos de los inhibidores de la enzima convertidora de angiotensina (iECA) en pacientes con demencia debido a la enfermedad de Alzheimer. MÉTODOS: Fueron reclutados pacientes consecutivos mayores de 60 años de edad con enfermedad de Alzheimer y sin antecedentes de trasplante renal o diálisis. Se determinaron correlaciones prospectivas durante un año entre los cambios en los niveles sanguíneos de urea y creatinina, considerando genotipos y haplotipos de ACE (rs1800764 y rs4291) y el tratamiento con iECA a y las variaciones en la presión arterial. RESULTADOS: De 190 pacientes, 152 presentaron hipertensión, 122 usaron iECA. Las frecuencias de alelos polimórficos fueron de 0.492 para rs1800764-C y 0.337 para rs4291-T, los dos alelos en equilibrio de Hardy-Weinberg. No se determinaron fluctuaciones anuales significativas en los niveles de urea o creatinina, pero sus variaciones concomitantes se asociaron fuertemente (ρ= <0.0001). Cada alelo A de rs4291 condujo a aumentos anuales de 3,074 mg/dL en urea y 0.044 mg/dL en creatinina, mientras que el uso de iECA fue protector para las variaciones en la creatinina. El uso de iECA también fue protector para las personas con rs1800764-CT/rs4291-AA, mientras que los portadores de rs1800764-CT/rs4291-AT tuvieron reducciones de creatinina más altas, particularmente cuando se usó iECA. CONCLUSIÓN: Los efectos de iECA en la variación de la creatinina son genéticamente mediadas e independiente de las variaciones en la presión arterial en pacientes de edad avanzada con la enfermedad de Alzheimer.
Subject(s)
Alzheimer Disease/blood , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Creatinine/blood , Peptidyl-Dipeptidase A/genetics , Urea/blood , Age Factors , Aged , Aged, 80 and over , Alleles , Blood Pressure/drug effects , Blood Pressure/genetics , Fasting/blood , Female , Gene Frequency , Genotype , Humans , Hypertension/drug therapy , Hypertension/genetics , Male , Middle AgedABSTRACT
Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding geneticallymediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Results: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3.074 mg/ dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Conclusions: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.
Antecedentes: El deterioro de la función renal depende de la edad y los factores vasculares. La literatura sobre los efectos de fármacos antihipertensivos mediada genéticamente en la función renal es pobre. Objetivo: Estimar las variaciones de urea y creatinina a través del análisis farmacogenético de los efectos antihipertensivos de los inhibidores de la enzima convertidora de angiotensina (iECA) en pacientes con demencia debido a la enfermedad de Alzhaimer. Métodos: Fueron reclutados pacientes consecutivos mayores de 60 años de edad con enfermedad de Alzheimer y sin antecedentes de trasplante renal o diálisis. Se determinaron correlaciones prospectivas durante un año entre los cambios en los niveles sanguíneos de urea y creatinina, considerando genotipos y haplotipos de ACE (rs1800764 y rs4291) y el tratamiento con iECA a y las variaciones en la presión arterial. Resultados: De 190 pacientes, 152 presenaron hipertensión, 122 usaron iECA. Las frecuencias de alelos polimórficos fueron de 0.492 para rs1800764-C y 0.337 para rs4291-T, los dos alelos en equilibrio de Hardy-Weinberg. No se determinaron fluctuaciones anuales significativas en los niveles de urea o creatinina, pero sus variaciones concomitantes se asociaron fuertemente (ρ= <0.0001). Cada alelo A de rs4291 condujo a aumentos anuales de 3.074 mg/dL en urea y 0.044 mg/dL en creatinina, mientras que el uso de iECA fue protector para las variaciones en la creatinina. El uso de iECA también fue protector para las personas con rs1800764-CT/rs4291-AA, mientras que los portadores de rs1800764-CT/rs4291-AT tuvieron reducciones de creatinina más altas, particularmente cuando se usó iECA. Conclusión: Los efectos de iECA en la variación de la creatinina son genéticamente mediadas e independiente de las variaciones en la presión arterial en pacientes de edad avanzada con la enfermedad de Alzheimer.
