A case of sporadic Pick disease with onset at 27 years.

BACKGROUND: Pick disease is an uncommon cause of dementia in middle age, and young-onset cases have rarely been reported. SETTING: A specialist hospital. PATIENT: Patient with onset of cognitive impairment at the age of 27 years whose cerebral biopsy specimen demonstrated Pick cells and tau-positive Pick bodies. CONCLUSION: Pick disease should be considered in the differential diagnosis of dementia in young adults.     

Autopsy proven sporadic frontotemporal dementia due to microvacuolar-type histology, with onset at 21 years of age

We describe the clinical, neuropsychological, and neuropathological features of a 21 year old woman with frontotemporal dementia (FTD). The early presentation was of florid behavioural change involving hyperactivity and disinhibition. Magnetic resonance imaging and single photon emission computed tomography of the brain revealed atrophy and severe functional abnormalities of the frontal and temporal lobes, respectively. Electroencephalogram was normal. At autopsy, there was gross frontotemporal brain atrophy and the underlying histology was of a microvacuolar-type degeneration; no tau or ubiquitin immunoreactive, intraneuronal inclusions were seen. There was no family history of dementia and no mutation in the tau gene. We believe this patient represents the youngest (so far) recorded case of FTD associated with this particular histological form of the disorder.     

Apolipoprotein E epsilon4 and age at onset of sporadic and familial Alzheimer disease in Caribbean Hispanics

BACKGROUND: The primary effect of the apolipoprotein E epsilon4 (APOE epsilon4) allele is on the age at onset of Alzheimer disease (AD). OBJECTIVE: To investigate whether the presence of the APOE epsilon4 allele can account for the earlier age at onset of familial AD (FAD) compared with sporadic AD (SAD). DESIGN: Population-based, case series ascertained in a prospective study of aging and dementia in Medicare recipients aged 65 years or older. SETTING: Clinics in northern Manhattan and in the Dominican Republic and Puerto Rico. PARTICIPANTS: There were 680 Caribbean Hispanic subjects: 111 patients with FAD, with at least 1 family member with dementia; 163 patients with SAD; and 406 elderly persons without dementia or other illnesses. Main Outcome Measure Age at onset of dementia was examined in relation to frequency of APOE epsilon4. Sex, education, and medical risk factors for stroke, hypertension, diabetes, and heart disease were examined as effect modifiers. RESULTS: The mean age at onset of AD was significantly lower in FAD than in SAD, and a statistically significant dose effect of the APOE epsilon4 allele was present for age at onset in FAD (P = .001) but not in SAD. The age at onset in patients homozygous for the APOE epsilon4 allele with FAD and SAD was similar. Compared with SAD, the major difference was younger age at onset in patients with FAD who were heterozygous for the APOE epsilon4 allele and those without an APOE epsilon4 allele. CONCLUSIONS: Apolipoprotein E epsilon4 had a consistent lowering effect on age at onset of FAD, but this was attenuated in SAD. This suggests that among individuals with a family history of AD and the APOE epsilon4 allele, additional genetic or environmental factors may accelerate the onset of dementia.     

Influence of monocyte chemoattractant protein 1 gene polymorphism on age at onset of sporadic Parkinson's disease.

We studied polymorphisms in the genes for monocyte chemoattractant protein 1 (MCP-1) and CC chemokine receptor (CCR)-2 in 171 Parkinson's disease (PD) patients and 340 controls. Although no associations were found in alleles or genotypes, MCP-1 -2518A/G genotype affected the age-at-onset of PD patients. This effect was also detected in a second PD group, suggesting a possible involvement of MCP-1 in PD.     

Later age at onset in Parkinson's disease over twenty years in an Italian tertiary clinic

BackgroundAge is considered an important risk factor for Parkinson's disease (PD). However, although life-expectancy has increased considerably, incidence rates of PD appeared to be stable over the last two decades. Accordingly, an increase in mean age at onset over time could be expected. We investigated the changes in age at onset in PD over the last two decades.MethodsAll consecutive PD patients assessed over a 18-year period (1995–2013) in a single tertiary outpatient clinic were included in the present retrospective cohort study.ResultsAfter adjusting for several confounders (gender, positive family history for PD, education, smoking at onset and past exposure to environmental/occupational pollutants), 5-year cohorts of year of disease onset were associated with increasing age at onset in both prevalent (N = 6996) and incident (N = 4172) cases (for trend, P < 0.001). From 1995–2000 to 2010–2013 there was an increase in predicted age of 4.1 years (95% CI, 3.0–5.2) and 3.9 years (95% CI, 2.7–5.1) in prevalent and incident cases, respectively. However, the change in predicted age at PD onset, across cohorts of year at onset, showed a steeper increase than the corresponding sex and cohort-matched mean age from the official Italian statistics.ConclusionsOver the last two decades, age at onset of PD appeared to shift progressively towards more advanced age. However, sequential, high-quality population-based incidence studies are required. To establish whether there is a trend towards increase in age at onset over and above general population ageing and to assess whether the increase is associated with improved medical and socio-economic conditions.     

Variability of age at onset in siblings with familial Alzheimer disease

BACKGROUND: Variability of age at onset (AO) of Alzheimer disease (AD) among members of the same family is important as a biological clue and because of its clinical effects. OBJECTIVE: To evaluate which clinical variables influence the discrepancy in AO among affected relatives with familial AD. SETTING: Clinical genetic project of Spanish kindred with AD conducted by 4 academic hospitals in Madrid, Spain. METHODS: Age at onset of AD in 162 families and discrepancy in AO in intragenerational and intergenerational affected pairs were analyzed in relation to age, sex, maternal or paternal transmission, pattern of inheritance, and apolipoprotein E genotype. RESULTS: Maternal transmission of AD was significantly more frequent than paternal transmission (P < .001). In 27% of the affected individuals, AO occurred before the patient was 65 years old. Discrepancy in AO among siblings was within 5 years in 44% of the families, 6 to 10 years in 29%, and more than 10 years in 27% (range, 0-22). This discrepancy was independent of the sex of the sibling pairs and was significantly lower with maternal transmission of AD (P = .02). Segregation analysis showed no differences in the inheritance pattern between families with low (< or =5 years) or high (>5 years) AO discrepancy. Age at onset in carriers of the apolipoprotein E epsilon4 allele was slightly younger. However, among siblings, an extra apolipoprotein E epsilon4 allele was not consistently associated with earlier onset of AD. Eighty percent of patients, independent of sex or mode of transmission, were already affected at their parents' reported AO. CONCLUSIONS: There is a wide discrepancy in AO in affected siblings that is not clearly explained by a single clinical variable or apolipoprotein E genotype. The interaction of many factors probably determines AO in each affected individual. However, maternal transmission of AD seems to result in a similar AO in offspring, and the risk of developing dementia after the parent's reported AO decreases significantly.     

Autopsy-proven Huntington's disease with 29 trinucleotide repeats.

Huntington's disease (HD) is a neurodegenerative disorder associated with expansion of CAG trinucleotide repeats in the huntingtin gene. A minimum of 36 CAG repeats is usually reported in patients with clinical features of HD; 30 to 35 repeats represent an intermediate range. Here we report a 65-year-old male with autopsy-proven HD and 29 CAG repeats.     

Age at menopause predicts age at onset of Parkinson's disease.

We investigated the association between age at onset of Parkinson's disease (PD) and fertile life characteristics in 145 women. Linear regression analyses showed a significant correlation between age at PD onset and age at menopause (P = 0.003), between age at PD onset and fertile life duration (P = 0.008), and a nonsignificant correlation between PD onset and cumulative duration of pregnancies (P = 0.23). These results support the possible role of estrogens in PD.     

Reliability of reported age at onset for Parkinson's disease.

An individual's age at onset of Parkinson disease (PD) can be collected through a variety of sources, including medical records, family report, and clinical observation. The most common source of PD age at onset information in the research setting is family-report, which is then typically used to classify a subject as juvenile, young, or late age at onset. The reliability of the family-reported age at onset of PD has not been rigorously examined. The present study used data from individuals diagnosed with PD to evaluate the reliability of age at onset information by comparing data obtained from three sources: 1) the subject's medical records, 2) a Family History Questionnaire, and 3) a Subject History Questionnaire. Among the 149 subjects with data for all three age at onset sources, the estimated reliability was R = 0.94. Similar reliability was observed when the sample was stratified based on gender, age at examination, disease duration, first symptom of PD, and years of education. The three measures of age at onset of PD show excellent agreement, strengthening confidence in the reliability of the reported age of clinical onset for PD.     

HLA A2 allele is associated with age at onset of Alzheimer's disease

The prevalence of the HLA A2 allele was investigated in a group of Italian patients with sporadic and early-onset familial Alzheimer's disease (AD and FAD) to analyze the potential association of this allele with early age of onset of the disease. The possible interaction between the HLA A2 allele and apolipoprotein E epsilon4 allele was analyzed. Our data suggest that A2 and epsilon4 alleles may have additive effects on AD onset, and that A2 may play an important role in determining or contributing to a very early age at onset. These findings further support the hypothesis of the involvement of an immune/inflammatory mechanism in the pathogenesis of AD.     

育龄期起病的女性帕金森病患者的临床特点

目的调查育龄期女性帕金森病(PD)患者发病的相关影响因素。方法采用调查问卷,连续选取202例发病时处于育龄期的女性PD患者,同时收集年龄、文化程度匹配的健康女性208名进行对照比较。分别收集两组人群的年龄、月经史、生育史、自然绝经年龄、患妇科疾病、妇科手术史、贝克焦虑量表等临床资料。同时记录PD组发病年龄、病程、统一帕金森病评分量表-Ⅲ(UPDRS-Ⅲ)评分、改良Hoehn-Yahr(H-Y)分级、受经期影响的人数及临床特征。结果两组患者在痛经史、流产史、患妇科疾病及手术、焦虑情绪比较差异有统计学意义(P0.05),在初潮年龄、月经周期、是否规律、有无服用避孕药比较差异无统计学意义(P0.05);PD组已绝经88例,平均(46.8±3.0)岁,对照组已绝经93例,平均(49.6±2.9)岁,PD组绝经年龄小于对照组(P0.01);PD组有54例患者受经期影响,占26.7%,均表现为临床症状的恶化。结论绝经时间早、流产次数多、有痛经史、既往有妇科肿瘤及相关手术史可能是育龄期妇女患PD风险增多的影响因素。     

Differences in duration of Huntington's disease based on age at onset

OBJECTIVES—Data from asample of 2494 patients affected with Huntington's disease (HD),collected as part of the National Research Roster for HuntingtonDisease Patients and Families, were examined to determine if there wasa relation between age at onset and duration of illness.
METHODS—Sufficientdata for inclusion in analysis was available from 2068 patients, ofwhom 828 were deceased and 1240 were living. The median duration ofdisease was 21.4 years with a range of 1.2 to 40.8 years. Patients werecategorised into one of four groups based on their age at onset.
RESULTS—Significantdifferences in duration based on the age at onset were found(p<0.025), with juvenile and late onset patients with HD havingshorter duration of illness compared with those with an onset between20-49 years.
CONCLUSIONS—Durationof disease is influenced by the age at symptom onset with juvenile andlate onset patients having the shortest duration.