P.N. Wang

Effects of estrogen on cognition, mood, and cerebral blood flow in AD A controlled study

Objective: To examine the effects of estrogen therapy on cognition, mood, and cerebral blood flow in patients with AD. Background: Some studies have suggested estrogen may be effective in the treatment of AD. However, most of these studies were not controlled adequately. Methods: Fifty female AD patients were recruited in a randomized, double-blind, placebo-controlled 12-week trial. Each member of the estrogen-treated group received conjugated estrogen (Premarin) 1.25 mg/day. The primary outcome measures were the Cognitive Ability Screening Instrument (CASI), Clinical Dementia Rating (CDR), and Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary outcome measures were Behavioral Pathology in Alzheimer’s Disease (BEHAVE-AD), Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale (HDRS), and 99mTc hexamethylpropylene amine oxime SPECT of the brain. Results: No meaningful differences were found between the outcome measures (CASI, CDR, CIBIC-plus, BEHAVE-AD, HARS, HDRS, and cerebral blood flow) taken from the estrogen-treated group and those from the control group. Conclusion: A 1.25-mg/day dose of Premarin administered for 12 consecutive weeks does not produce a meaningful effect on cognitive performance, dementia severity, behavior, mood, and cerebral perfusion in female AD patients. Because estrogen therapy has been suspected of yielding adverse effects, and its therapeutic effectiveness is in doubt, additional evaluation of its role in AD treatment ought to be conducted.

Chronic daily headache in Chinese elderly: Prevalence, risk factors, and biannual follow-up

Objective: To investigate the prevalence, risk factors, and prognosis of chronic daily headache (CDH) in a population of elderly Chinese subjects. Methods: A community-based survey of registered residents ≥65 years old (n = 2,003) in two townships of Kinmen Island in 1993. A neurologist used a structured questionnaire and clinical interview to make the diagnosis of headache. Subjects who had headaches ≥15 days/month for ≥6 months in the previous year were considered to have CDH. CDH was further classified into chronic tension-type headache (CTTH), CDH with migrainous features (CDH/MF), and other CDH. Person-to-person biannual follow-up of the subjects with CDH was done in June 1995 and August 1997. Results: A total of 1,533 people (77%) participated in our prevalence study. Sixty subjects (3.9%) fulfilled the criteria for CDH, with a higher prevalence in women (F/M: 5.6%/1.8%, p < 0.001). Of these subjects, 42 (70%) had CTTH, 15 (25%) had CDH/MF, and 3 (5%) had other CDH. Only 23% of those with CDH had consulted physicians for their headaches in the previous year. Multivariate logistic regression revealed the significant risk factors for CDH to be analgesic overuse (OR = 79), a history of migraine (OR = 6.6), and a Geriatric Depression Scale–Short Form score of ≥8 (OR = 2.6). The follow-up results in 1995 and 1997 showed that about two-thirds of the subjects still had CDH. Analgesic overuse (relative risk = 1.6) in 1993 was a significant predictor of persistent CDH at follow-up. Conclusions: A total of 3.9% of this elderly population had CDH, with CTTH being the most common subtype. Almost two-thirds of those with CDH had persistent frequent headaches at follow-up. Analgesic overuse was a significant predictor of a poor outcome.

Depressive disorders among older residents in a Chinese rural community

BACKGROUND Two recent surveys of depression among Chinese elderly people sampled different populations, used different case ascertainment methods and resulted in a seven-fold difference in prevalence rates. The present study was conducted to compare prevalence rates obtained with two commonly used methods in the same population, and to examine the risk factors for depression. METHODS The target population included all residents aged 65 years and over in a rural Chinese community. Participants were interviewed for demographic and medical information, examined by a neurologist and administered Chinese versions of the Geriatric Depression Scale-Short Form (GDS-S), the Cognitive Abilities Screening Instrument (CASI) and an Activities of Daily Living (ADL) form. Individuals who screened positive on the GDS-S were also interviewed by a psychiatrist for diagnosis according to the DSM-III-R criteria. RESULTS Among the 1313 participants, 26% screened positive on the GDS-S and 13% were diagnosed as having a depressive disorder, including 6.1% with major depression. Individuals with depressive disorders were more likely to have poor ADL scores, lower CASI scores, and chronic physical illnesses. They were also more likely to be female, older, illiterate and without a spouse, but adding these variables did not increase the overall association with the GDS-S score. CONCLUSIONS Depression was quite common in this Chinese rural geriatric population. The prevalence rate was twice as high when judged by depression symptomatology rather than clinical diagnosis. The critical risk factors were functional impairments, poor cognitive abilities and the presence of chronic physical illnesses.

Patients’ versus caregivers’ report of poor memory in relation to dementia and tested abilities

Complaints of poor memory are common among older individuals, but their clinical significance remains unclear. We compared patients’ self-report of poor memory with their caregivers’ report, and to compare the two reports’ associations with the patients’ dementia status and tested cognitive performance. Participants included 709 patients at the Memory Clinic of the Taipei Veterans General Hospital and their primary caregivers. A total of 493 of the patients were diagnosed with dementia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV),1 including 78% with probable AD, 15% with vascular dementia, and 7% with mixed or other types of dementia. The diagnosis of dementia and its subtypes was made by a neurologist based on interview, physical examination, cognitive test, and laboratory findings. Each patient and caregiver was asked separately by a neuropsychologist to describe the patient’s memory as being good/average or poor. They also answered questions for the …

ApoE genotype in relation to AD and cholesterol A study of 2,326 Chinese adults

Objective: To calculate the frequencies of apolipoprotein E (apoE) alleles in a large Chinese community sample and to compare the serum cholesterol levels of ε2, ε3, and ε4 carriers. Background: In comparison with Western populations, a lower frequency of the apoE ε4 allele among the Chinese has been proposed as one factor for the lower prevalence of AD found in Chinese populations, but there are insufficient Chinese data on ε4 frequency that are based on large community samples. In addition, although Western studies have repeatedly found a lower cholesterol level in ε2 carriers and a higher cholesterol level in ε4 carriers in comparison with ε3 homozygotes, two Chinese studies have yielded inconsistent findings between them. Methods: During the incidence phase of an epidemiologic survey of several neurologic disorders in a Chinese community, the authors took blood samples from 2,326 participants to determine the apoE genotypes and to measure cholesterol levels. Results: The allelic frequencies of ε2, ε3, and ε4 were 11.8%, 76.4%, and 11.8% among 17 AD patients, and 7.8%, 84.1%, and 8.1% for the entire sample. The mean cholesterol level of the ε2 carriers was significantly lower, and that of the ε4 carriers significantly higher, than that of the ε3 homozygotes. Conclusions: The obtained ε4 rate of 8.1% is lower than most of the Western findings, and this may account in part for the lower prevalence of AD found among the Chinese. The associations between the apoE genotype and serum cholesterol level are similar between Chinese and white populations.

Comparison of cerebellar ataxias: A three-year prospective longitudinal assessment.

We quantitatively investigated the clinical severity and progression of diseases with ataxia, as measured with the Scale for the Assessment and Rating of Ataxia, and examined the potential application of the Scale for the Assessment and Rating of Ataxia for future therapeutic trials. Severity of ataxia was assessed in 238 patients with spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, spinocerebellar ataxia type 6, spinocerebellar ataxia type 17, multiple system atrophy‐cerebellar variant, or Gerstman‐Sträussler‐Scheinker disease. Among them, 119 (50%) were longitudinally examined three to seven times, in a period of 8 to 38 months, resulting in a total set of 535 assessments. The differences between spinocerebellar ataxia and multiple system atrophy‐cerebellar variant were ascertained cross‐sectionally and longitudinally. Gerstman‐Sträussler‐Scheinker disease had the fastest progression, followed by multiple system atrophy‐cerebellar variant, spinocerebellar ataxia type 17, spinocerebellar ataxia type 3, spinocerebellar ataxia type 2, and spinocerebellar ataxia type 6. Patients with multiple system atrophy‐cerebellar variant had a faster progression in gait, sitting, speech, and total score than patients with spinocerebellar ataxias. For a randomized, case‐control trial, a sample size of 47 for spinocerebellar ataxia and 85 for multiple system atrophy‐cerebellar variant in the treatment or placebo arms would have a sufficient statistical power to demonstrate the efficacy of a new therapy that would retard ataxia progression by 1 point per year as measured by the Scale for the Assessment and Rating of Ataxia. The results will have a significant impact on the planning and implementation of future therapeutic trials of spinocerebellar ataxia and multiple system atrophy‐cerebellar variant.

Selective Hypoperfusion of Anterior Cingulate Gyrus in Depressed AD Patients: A Brain SPECT Finding by Statistical Parametric Mapping

This study tests the hypothesis that depression in patients with Alzheimer’s disease (AD) is due to a specific pathogenesis rather than a reactive phenomenon. Forty-three AD patients received a psychiatrist’s interview, neuropsychological assessments, and a 99mTc-hexamethyl propyleneamine oxime single photon emission computed tomography (HMPAO-SPECT). Analysis by statistical parametric mapping (SPM) showed that the depressed group had selective hypoperfusion in the bilateral anterior and posterior cingulate gyri and precuneus. Using the Hamilton Depression Rating Scale as a parameter, an inverse correlation was found between cerebral perfusion and the severity of depression. The right anterior cingulate gyrus demonstrated a most significant reduction in perfusion. These locations are akin to the imaging findings in patients with primary depression, indicating a specific pathogenesis for depression in AD.

Acute Disseminated Encephalomyelitis in Middle-Aged or Elderly Patients

Acute disseminated encephalomyelitis (ADEM) in middle-aged or elderly adults is rarely reported. We present here three ADEM patients of these age groups, who manifested behavioral changes, mutism or psychosis. Single clinical episodes, widespread encephalopathic disturbances and magnetic resonance imaging (MRI) findings favored the diagnosis of ADEM. However, no obvious preceding infections could be discovered. Two of them had traveled to mainland China prior to admission to psychiatric wards. All three patients had fair-to-good recovery after steroid treatment. A review of the literature showed that clinical and neuroimage findings of ADEM in the elderly group did not differ from those in the younger group. However, ADEM has rarely been reported in older age groups, probably due to: (1) differences between the elderly and young people in susceptibility or immune response to infectious agents, and (2) lack of a sensitive tool to examine patients prior to the wide-spread use of MRI. We suggest ADEM as one of the possible etiologies of acute or subacute onset of psychosis in adult patients, especially in those with a history of traveling.

Estrogen-Metabolizing Gene COMT Polymorphism Synergistic APOE ε4 Allele Increases the Risk of Alzheimer Disease

Alzheimer disease (AD) is a polygenic multifactorial disorder. Several studies suggested that the neuroprotective effect of estrogen was based on an APOE-dependent mechanism. The goals of the current study were to determine if the genes involved in estrogen metabolism were linked to the risk of AD and find out if there was an interaction between estrogen-metabolizing gene polymorphisms and the APOE Ε4 allele in the risk of prevalent AD. We investigated 66 patients with AD and 86 age- and gender-matched normal subjects. The polymorphisms of APOE and estrogen-metabolizing genes CYP17, CYP1A1 and COMT were examined. No association was found between each estrogen-metabolizing gene polymorphism and AD. However, the COMT HH genotype and APOE Ε4 allele had a synergistic effect on the risk of AD. Taking subjects with Ε4–Ε4–/HH– as reference, the risk of developing AD in subjects with one Ε4 allele (Ε4+Ε4–/HH–) was 2.6 (95% confidence interval, CI, 0.7– 9.1); however, the risk in subjects with both HH and one Ε4 (Ε4+Ε4–/HH+) increased to 3.6 (95% CI 1.2–10.6). The subjects with homozygous Ε4 still had the highest risk in developing AD (odds ratio 6.6, 95% CI 0.6–69.6). The p value of the linear trend test for this regression model was 0.004. It is possible that a high metabolism of estrogen by COMT may have reduced the protective effect of estrogen in AD. Further studies to clarify this interaction may improve our understanding of the generic risks for AD.

ApoE 4 allele is associated with incidental hallucinations and delusions in patients with AD

Of 135 patients with Alzheimer disease (AD), 56 without psychiatric symptoms at the first visit were followed for a mean period of 51.9 ± 10.3 months to identify incident psychiatric symptoms. The hazard ratios of ApoE ε4 allele in developing psychiatric symptoms were calculated by Cox regression hazard analyses. The presence of the ApoE ε4 allele carried a 19.0-fold risk for developing hallucinations and a 3.4-fold risk for delusions.