Alzheimer Disease: Folstein MF

Qiu WQ, Folstein MF. · Department of Psychiatry, New England Medical Center and Tufts University School of Medicine, 150 Harrison Avenue, Rm 234, Boston, MA 02111, USA. · Neurobiol Aging. · Pubmed #16399206 No free full text.

Abstract: Clinical and epidemiological studies have found that type 2 diabetes, and hyperinsulinaemia, increased the risk of developing Alzheimer's disease (AD) in the elderly. The link between hyperinsulinaemia and AD may be insulin-degrading enzyme (IDE). This enzyme degrades both insulin and amylin, peptides related to the pathology of type 2 diabetes, along with amyloid-beta peptide (Abeta), a short peptide found in excess in the AD brain. We review the current evidence, which suggests that hyperinsulinaemia may elevate Abeta through insulin's competition with Abeta for IDE. Genetic studies have also shown that IDE gene variations are associated with the clinical symptoms of AD as well as the risk of type 2 diabetes. The deficiency of IDE can be caused by genetic variation or by the diversion of IDE from the metabolism of Abeta to the metabolism of insulin. It is intriguing to notice that both hyperinsulinaemia and IDE gene variations are related to the risk of AD when the Apolipoprotein E4 (ApoE4) allele, the major risk factor of late-onset AD, is not present. Further studies of the role of IDE in the pathogenesis of AD, which may uncover potential treatment target, are much needed.

Scott TM, Tucker KL, Bhadelia A, Benjamin B, Patz S, Bhadelia R, Liebson E, Price LL, Griffith J, Rosenberg I, Folstein MF. · Department of Psychiatry, Tufts-New England Medical Center, and Tufts University School of Medicine, Boston, MA 02446, USA. · Am J Geriatr Psychiatry. · Pubmed #15545331 No free full text.

Abstract: OBJECTIVE: There is a growing literature on the relationship between low serum B-vitamins, elevated homocysteine, and cognitive impairment; however, few studies have examined radiological markers of associated neuropathology in geropsychiatry inpatients. The authors examined the relationship of homocysteine, folate, and vitamin B12 with magnetic resonance imaging (MRI) markers of neuropathology. METHODS: In this archival study, authors reviewed the MRIs and medical records of 34 inpatients in a geriatric psychiatry unit. Patients were selected if folate, B12, and/or homocysteine levels had been assessed and if the appropriate clinical MRIs were performed (19 men; mean age, 75 years). Patients with schizophrenia or current substance dependence were excluded. The relationships between MRI volume measures, white-matter hyperintensity (WMH) grade, and serum concentrations of folate, B12, and homocysteine were analyzed, using age-adjusted Pearson correlations. RESULTS: Homocysteine was related to WMH grade, but not brain-volume measures. Folate was associated with hippocampus and amygdala, and negatively associated with WMH. B12 level was not statistically associated with any brain measure. CONCLUSIONS: Elevated homocysteine and low folate were associated with radiological markers of neuropathology. Since no patient had clinically deficient folate, it may be important to rethink what defines functionally significant micronutrient deficiency and explore what this means in different age- and health-status groups. Larger samples will be needed to assess interactions between homocysteine, micronutrients, and other neuropathology risk factors.

Blacker D, Bertram L, Saunders AJ, Moscarillo TJ, Albert MS, Wiener H, Perry RT, Collins JS, Harrell LE, Go RC, Mahoney A, Beaty T, Fallin MD, Avramopoulos D, Chase GA, Folstein MF, McInnis MG, Bassett SS, Doheny KJ, Pugh EW, Tanzi RE, Anonymous00039. · Massachusetts General Hospital, Charlestown, MA, USA. · Hum Mol Genet. · Pubmed #12490529 links to  free full text

Abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22-met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) >/=1.9 and/or multipoint lod score (MLS) >/=2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.

Rapp MA, Rieckmann N, Gutzmann H, Folstein MF. · Krankenhaus Hellersdorf, Abteilung für Gerontopsychiatrie, Berlin, Germany. · Nervenarzt. · Pubmed #12215874 No free full text.

Abstract: Especially in outpatient settings, dementia is still an underdiagnosed syndrome. The Micro-Mental Test has been developed as a short version of the Mini-Mental-Status Examination (MMSE). We examined the reliability and diagnostic validity of a German version (Mikro-Mental Test). We administered the MMSE and the German version of the Micro-Mental Test to 20 inpatients of a geriatric psychiatry hospital (mean age 74.8+/-8.1 years), 55 patients from a cognitive clinic (mean age 71.9+/-9.1 years), and 27 healthy older adults (mean age 68.5+/-4.1 years). Diagnoses made by an experienced psychiatrist according to ICD-10 criteria served as external criteria. The mean duration for testing with the Micro-Mental Test was 8 min, and with the MMSE 15 min. Test-retest analyses showed satisfactory reliability. With regard to sensitivity and specificity, we found comparable diagnostic validity for the MMSE and the Micro-Mental Test. We suggest that, due to its brevity and diagnostic validity, the Micro-Mental Test is a useful tool for dementia screening in an outpatient setting.

Grodstein F, Chen J, Pollen DA, Albert MS, Wilson RS, Folstein MF, Evans DA, Stampfer MJ. · Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · J Am Geriatr Soc. · Pubmed #10894312 No free full text.

Abstract: OBJECTIVE: Accumulating biologic evidence suggests that estrogen is related to cognitive function. Several epidemiologic investigations have reported that hormone therapy may reduce the risk of Alzheimer's disease. However, fewer studies have examined the relation of postmenopausal hormone use to general cognitive function in nondemented older women. Thus, we examined the association of hormone therapy to performance on four cognitive tests among healthy participants of the Nurses' Health Study. DESIGN: Cohort study. SETTING: The Nurses' Health Study, an ongoing prospective cohort study begun in 1976. PARTICIPANTS: From the Nurses' Health Study, 2138 women aged 70-78 years. MEASUREMENTS: From 1995-1999 we administered four cognitive tests (Telephone Interview for Cognitive Status (TICS), immediate and delayed recall of the East Boston Memory Test (EBMT), and verbal fluency) by telephone. Hormone use was ascertained from biennial questionnaires beginning in 1976. Linear and logistic regression models were used to calculate multivariate-adjusted differences in scores and relative risks of a low score for never users compared to current and past hormone users. RESULTS: After adjustment for confounders, neither current nor long-term hormone users demonstrated better performance on an overall measure of cognition (TICS), or on three tests of verbal memory (immediate and delayed recall of the EBMT, immediate recall of the TICS 10-word list) than never users. On the test of verbal fluency, current hormone users scored significantly better than never users (linear regression estimate of the difference in score = 0.78 points, 95% confidence interval (CI) 0.19-0.38, P = .01 for any current use; and 0.91 points, 95% CI 0.28-1.54, P = .005 for > or = 5 years current use). Current hormone users also had a 30% decrease (RR = 0.70, 95% CI 0.45-1.09) in their risk of a low score on the test of verbal fluency. These results were similar for women taking estrogen alone and estrogen combined with a progestin. CONCLUSIONS: Verbal fluency may be enhanced among women taking postmenopausal hormones, however, there is little support for better overall cognitive function in hormone users than nonusers.