Prevalence, assessment and diagnosis
In young men, various risk factors are associated with later development of young-onset dementia doi:10.1136/eb-2013-101627
QUESTION Question: What non-genetic risk factors in late adolescence and young adulthood are associated with the development of young-onset dementia (YOD) in men in later life? People: 488 484 Swedish men conscripted for mandatory military service (mean age 18 years) from September 1969 through December 1979. Men were excluded for extreme body weight (170 kg) or height (215 cm). Setting: Sweden; 1969–2011. Risk factors: Cognitive function (scored on a range from 1 to 40, assessed by summing the normalised z-scores of a logic test, a word recollection test, a visuospatial test and a technical test assessing problem-solving capacity), year of conscription, age, height and weight, knee muscle strength and blood pressure (BP) were assessed during standardised cognitive and physical examinations at time of conscription. Annual income and education level were assessed 15 years after conscription using the Statistics Sweden database. Diagnoses of alcohol intoxication, other drug intoxication, depression or use of antidepressants, myocardial infarction, stroke, use of antipsychotic or antidiabetic medication and parental diagnosis of dementia were assessed using the Swedish National Hospital Discharge Patient Register (NPR) at follow-up. Outcomes: Diagnosis of YOD, as recorded in the Swedish National Hospital Discharge Patient Register (NPR) using International Statistical Classification of Diseases (ICD) codes for vascular dementia, alcohol dementia and dementia associated with Parkinson disease, Lewy body dementia and dementia of unspecified type. Association between risk factors and YOD were calculated using analysis of variance with a Bonferroni correction. Cox proportional HR were calculated for independent risk factors and population attributable risk (PAR) was calculated from a Cox proportional hazards regression model.
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Evid Based Mental Health May 2014 Vol 17 No 2
MAIN RESULTS During the follow-up period, a total of 487 men were diagnosed with YOD (average age at diagnosis 54 years). Nine independent risk factors were found to be significantly associated with a YOD diagnosis: alcohol intoxication, stroke, use of antipsychotics, depression, father’s dementia, non-alcohol drug intoxication, low-height and low-cognitive function at time of conscription were associated with significantly increased risk of YOD in later life, while low systolic BP was associated with significantly reduced risk (see online table 1 for HR and PAR for each risk factor). Joint analysis revealed that men in the lowest tertile of cognitive function who had at least two of the risk factors had significantly increased risk of YOD compared with men in the highest tertile of cognitive function (HR 20.38, 95% CI 13.64 to 30.44). CONCLUSIONS Various risk factors in young men are associated with the later development of young onset dementia. The effects of these risk factors are multiplicative. Most of them are potentially modifiable and may be detectable in adolescence. NOTES Incarcerated men and those with documented severe chronic medical conditions or disabilities were exempt from conscription. ABSTRACTED FROM Nordström P, Nordström A, Eriksson M, et al. Risk factors in late adolescence for young-onset dementia in men: a nationwide cohort study. JAMA Intern Med 2013;173:1612–18. Correspondence to Peter Nordstrom, Department of Community Medicine and Rehabilitation, Geriatric Medicine, 90187 Umea University, Umea, Sweden. peter. [email protected] Sources of funding The Swedish Research Council and the Swedish Dementia Foundation.
arising in mid-life is more common than is generally recognised. The risk factors in this study were intoxication with alcohol and other drugs in youth, stroke, neuroleptic use, depression, paternal dementia, low cognition at conscription, high systolic blood pressure at conscription and low height at conscription. These factors were multiplicative, but alcohol intoxication in youth had the highest attributable risk and was linked to alcohol dementia, vascular dementia and unspecified types. Substance abuse and hypertension are common, modifiable and preventable, and thus point to potential opportunities in primary care to do dementia prevention. Linkages between mid-life dementia, depression and neuroleptic use also suggest opportunities for preventive intervention. Questions remain, nonetheless. Prospective studies using physiological markers are needed to (1) ask whether depression, low cognition and substance abuse are high-risk states or prodromes, (2) whether alcohol-related dementia arises from toxic effects of alcohol or
nutritional deficiencies4 and (3) link-specific variables to specific dementia types. Chiadi U Onyike Johns Hopkins University, Baltimore, Maryland, USA Competing interests None.
REFERENCES 1.
2.
3.
4.
Mendez MF, Lee AS, Joshi A, et al. Nonamnestic presentations of early-onset Alzheimer’s disease. Am J Alzheimers Dis Other Dement 2012;27:413–20. Baugh CM, Stamm JM, Riley DO, et al. Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav 2012;6: 244–54. Harvey R, Skelton-Robinson M, Rossor M. The prevalence and causes of dementia in people under the age of 65 years. J Neurol, Neurosurg Psychiatry 2003;74:1206–9. Ridley NJ, Draper B, Withall a alcohol-related dementia: an update of the evidence. Alzheimers Res Ther 2013;5:3.
49
Commentary
ecognition of youth and mid-life presentations of dementia is increasing. Young-onset dementia (YOD; ie, dementia arising before age of 65) differs in respects from late-life dementia. It is frequently a non-amnesic state.1 A substantial proportion stem from hereditary mutations, but the majority are sporadic occurrences. Head trauma is the only established risk factor for YOD2 and applies to a fraction of the cases. Nordström and colleagues sought risk factors from a large cohort of men conscripted at the age of 18 for military service during a 10-year period, and observed for up to 41 years. Linkage of a military service register to national clinical databases facilitated collation of baseline cognitive and physical examination data, later clinical diagnoses and prescription data, family dementia history and demographic variables. The breadth of these data enabled description of dementia frequency and risk factors in the cohort. The prevalence of YOD was similar to that from an earlier report from the UK3 indicating that dementia
METHODS Design: Retrospective cohort study. Follow-up period: Up to 41 years.
Copyright of Evidence Based Mental Health is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
In young men, various risk factors are associated with later development of young-onset dementia doi:10.1136/eb-2013-101627
QUESTION Question: What non-genetic risk factors in late adolescence and young adulthood are associated with the development of young-onset dementia (YOD) in men in later life? People: 488 484 Swedish men conscripted for mandatory military service (mean age 18 years) from September 1969 through December 1979. Men were excluded for extreme body weight (170 kg) or height (215 cm). Setting: Sweden; 1969–2011. Risk factors: Cognitive function (scored on a range from 1 to 40, assessed by summing the normalised z-scores of a logic test, a word recollection test, a visuospatial test and a technical test assessing problem-solving capacity), year of conscription, age, height and weight, knee muscle strength and blood pressure (BP) were assessed during standardised cognitive and physical examinations at time of conscription. Annual income and education level were assessed 15 years after conscription using the Statistics Sweden database. Diagnoses of alcohol intoxication, other drug intoxication, depression or use of antidepressants, myocardial infarction, stroke, use of antipsychotic or antidiabetic medication and parental diagnosis of dementia were assessed using the Swedish National Hospital Discharge Patient Register (NPR) at follow-up. Outcomes: Diagnosis of YOD, as recorded in the Swedish National Hospital Discharge Patient Register (NPR) using International Statistical Classification of Diseases (ICD) codes for vascular dementia, alcohol dementia and dementia associated with Parkinson disease, Lewy body dementia and dementia of unspecified type. Association between risk factors and YOD were calculated using analysis of variance with a Bonferroni correction. Cox proportional HR were calculated for independent risk factors and population attributable risk (PAR) was calculated from a Cox proportional hazards regression model.
R
Evid Based Mental Health May 2014 Vol 17 No 2
MAIN RESULTS During the follow-up period, a total of 487 men were diagnosed with YOD (average age at diagnosis 54 years). Nine independent risk factors were found to be significantly associated with a YOD diagnosis: alcohol intoxication, stroke, use of antipsychotics, depression, father’s dementia, non-alcohol drug intoxication, low-height and low-cognitive function at time of conscription were associated with significantly increased risk of YOD in later life, while low systolic BP was associated with significantly reduced risk (see online table 1 for HR and PAR for each risk factor). Joint analysis revealed that men in the lowest tertile of cognitive function who had at least two of the risk factors had significantly increased risk of YOD compared with men in the highest tertile of cognitive function (HR 20.38, 95% CI 13.64 to 30.44). CONCLUSIONS Various risk factors in young men are associated with the later development of young onset dementia. The effects of these risk factors are multiplicative. Most of them are potentially modifiable and may be detectable in adolescence. NOTES Incarcerated men and those with documented severe chronic medical conditions or disabilities were exempt from conscription. ABSTRACTED FROM Nordström P, Nordström A, Eriksson M, et al. Risk factors in late adolescence for young-onset dementia in men: a nationwide cohort study. JAMA Intern Med 2013;173:1612–18. Correspondence to Peter Nordstrom, Department of Community Medicine and Rehabilitation, Geriatric Medicine, 90187 Umea University, Umea, Sweden. peter. [email protected] Sources of funding The Swedish Research Council and the Swedish Dementia Foundation.
arising in mid-life is more common than is generally recognised. The risk factors in this study were intoxication with alcohol and other drugs in youth, stroke, neuroleptic use, depression, paternal dementia, low cognition at conscription, high systolic blood pressure at conscription and low height at conscription. These factors were multiplicative, but alcohol intoxication in youth had the highest attributable risk and was linked to alcohol dementia, vascular dementia and unspecified types. Substance abuse and hypertension are common, modifiable and preventable, and thus point to potential opportunities in primary care to do dementia prevention. Linkages between mid-life dementia, depression and neuroleptic use also suggest opportunities for preventive intervention. Questions remain, nonetheless. Prospective studies using physiological markers are needed to (1) ask whether depression, low cognition and substance abuse are high-risk states or prodromes, (2) whether alcohol-related dementia arises from toxic effects of alcohol or
nutritional deficiencies4 and (3) link-specific variables to specific dementia types. Chiadi U Onyike Johns Hopkins University, Baltimore, Maryland, USA Competing interests None.
REFERENCES 1.
2.
3.
4.
Mendez MF, Lee AS, Joshi A, et al. Nonamnestic presentations of early-onset Alzheimer’s disease. Am J Alzheimers Dis Other Dement 2012;27:413–20. Baugh CM, Stamm JM, Riley DO, et al. Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav 2012;6: 244–54. Harvey R, Skelton-Robinson M, Rossor M. The prevalence and causes of dementia in people under the age of 65 years. J Neurol, Neurosurg Psychiatry 2003;74:1206–9. Ridley NJ, Draper B, Withall a alcohol-related dementia: an update of the evidence. Alzheimers Res Ther 2013;5:3.
49
Commentary
ecognition of youth and mid-life presentations of dementia is increasing. Young-onset dementia (YOD; ie, dementia arising before age of 65) differs in respects from late-life dementia. It is frequently a non-amnesic state.1 A substantial proportion stem from hereditary mutations, but the majority are sporadic occurrences. Head trauma is the only established risk factor for YOD2 and applies to a fraction of the cases. Nordström and colleagues sought risk factors from a large cohort of men conscripted at the age of 18 for military service during a 10-year period, and observed for up to 41 years. Linkage of a military service register to national clinical databases facilitated collation of baseline cognitive and physical examination data, later clinical diagnoses and prescription data, family dementia history and demographic variables. The breadth of these data enabled description of dementia frequency and risk factors in the cohort. The prevalence of YOD was similar to that from an earlier report from the UK3 indicating that dementia
METHODS Design: Retrospective cohort study. Follow-up period: Up to 41 years.
Copyright of Evidence Based Mental Health is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
