Subcortical ischemic vascular disease and dementia (SIVD) incorporate small vessel disease as the chief vascular etiology, lacunar infarct and ischemic white-matter lesions (WMLs) as primary type of brain lesions, subcortical location as the primary location of lesions, and subcortical syndrome as the primary clinical manifestation. It incorporates two clinical entities: Binswanger's syndrome and the lacunar state. Patients with SIVD present with extensive white-matter lesions and multiple lacunae on neuroimaging. SIVD is expected to be a more homogenous subtype of vascular cognitive impairment and dementia. Recently modified NINDS-AIREN research criteria for SIVD have been proposed. Further empirical research is needed to refine the syndrome and stages and validate the brain imaging criteria, as well as to detail the natural history and outcomes of SIVD.

Alzheimer's disease (AD) is the most common neurodegenerative disease. There has been a rapid increase in the knowledge of epidemiology, genetics, risk factors, and underlying neuropathological mechanisms, but still there is no cure for AD. Recent promising studies with functional imaging using positron emission tomography (PET) and magnetic resonance imaging reveal that disease processes can be detected when very early subjective symptoms of AD are manifest. Recently the PET ligand PIB was reported to bind in vivo to β-amyloid in the brains of AD patients. Also cerebrospinal fluid markers including tau, phosphotau, and Aβ 1–42 are probably important early biological markers that will provide an early diagnosis of AD. An obvious impairment in central cholinergic transmitter function and its close relation to cognitive function led to the development of the acetylcholinesterase inhibitors that now are used as symptomatic therapy. A drug interfering with the glutaminergic brain transmitter system, the NMDA antagonist memantine, has recently been approved for the treatment of patients with severe AD. In order to stop or reverse disease progression, different AD treatment strategies are of great interest. Epidemiological studies support the hypothesis that long-term treatment with estrogen, antioxidants, anti-inflammatory drugs, and cholesterol-lowering agents could protect against the development of AD. Treatment with these drugs in manifest AD has been less promising. The use of nerve growth factors was limited by severe side effects. Much evidence supports the key role of β-amyloid in the pathogenesis of AD. Compounds such as amyloid β-sheet breakers, cholesterol-lowering drugs, estrogen, nicotine, zinc and copper chelators, inhibitors of β- and γ-secretases, and immunization to reduce the amyloid burden in transgenic mice over-expressing β-amyloid all have their advocates. The latter exciting strategy turned out to cause meningoencephalitis in 6% of AD patients so treated. One patient from the trial has died showing less β-amyloid burden in brain than expected and patients with serum β-amyloid plaque reactive antibodies had less cognitive decline after 1 year than AD patients without antibodies. There is a great optimism for early diagnosis and effective treatment of AD in the future.

Background and Objectives: Cerebral MRIs of normal aging and Alzheimer's disease (AD) frequently reveal corpus callosum (CC) atrophy, white matter hyperintensity (WMH), and hippocampal atrophy. However, their relationship between these findings and cognitive function has not been fully studied. We investigated the relationship between CC atrophy, WHM, and hippocampal atrophy, together with frontal executive dysfunction in both normal aging and AD. Method: We examined 170 randomly selected residents from a designated community: 99 Clinical Dementia Rating (CDR) 0 (healthy, control group, HC) participants, 54 CDR 0.5 (very mild AD) patients, and 17 CDR 1 & 2 (probable AD) patients. By means of MRI, WMH and CC atrophy were visually rated. Four portions of the CC and the hippocampal width were measured. A Mini-Mental State Examination and Cognitive Abilities Screening Instrument (CASI) were performed to assess global function. For the frontal function, the CASI subitems of attention and word fluency, letter-based fluency, the Digit Symbol test of the WAIS-R, and Trail Making Tests were performed. Results: Those patients with CDR 1 & 2 had both hippocampal and CC atrophy, whereas the CDR 0.5 patients had only hippocampal atrophy. Frontal executive dysfunction was associated with CC atrophy in both the HC and AD groups. Significant Spearman correlations were noted between CC atrophy and WMH in both groups. The combined effect of CC atrophy and WMH was noted only in the verbal fluency tests in the HC group. Conclusion: In both groups, CC atrophy was associated with frontal executive dysfunction. The combined effect of CC atrophy and WMH in normal aging was probably due to subclinical inschemic conditions.

Background: Activities of daily living (ADL) vary across cultures, and measure of ADL needs to be specific to the population under study. We developed an ADL measure for Thai elderly with dementia and investigated the reliability and validity of this instrument. Materials and Methods: Item construction was accomplished with a panel of neurologists and a rehabilitation medicine physician. One hundred eighty-one subjects were interviewed using the Thai ADL measure. Of this sample, one hundred fifty-nine had dementia according to the Diagnosic and Statistical Manual of Mental Disorders, fourth edition criteria. These data were analyzed for internal consistency; concurrent validity was determined by comparison with the Barthel Index, Functional Assessment Questionnaire (FAQ), Thai Mental State Exam (TMSE), and Clinical Dementia Rating (CDR) scale; and discriminant validity was determined by comparison with the Neuropsychiatric Inventory (NPI). Thirty subjects were tested to determine interrater and test-retest reliability. Results: Thai ADL measure was composed of six basic ADL and seven instrumental ADL. It had high correlation with TMSE scores (r = −.69), CDR scores (r = .81), Barthel Index scores (r = −.08), and FAQ scores (r = .88), and moderate correlation with NPI scores (r = .46). The instrument had high test-retest reliability (intraclass correlation coefficient [ICC] = .92, .89) and high interrater reliability (ICC = .96, .93). Conclusion: The Thai ADL scale is easy to use and it has high reliability. It had high concurrent validity with previously published ADL scales. The methodology used to develop the Thai ADL scale can provide a model for creating culturally competent ADL scales.

Background/Objective: The association between hypertension, diabetes, and worse cognitive function has been reported to be stronger in groups with low levels of education. Using data from a cross-sectional community survey of Korean elders, we sought to investigate this within a sample with relative cognitive impairment. Methods: The sample consisted of 341 participants with Mini-Mental State Examination (MMSE) (Korean version) scores of 24/30 or below. Previous diagnoses were ascertained and participants were examined for resting blood pressure and nonfasting blood glucose and cholesterol. Results: After adjustment for age, occupation, physical dependence, and cholesterol levels, worse cognitive function (MMSE score < 21) within the sample was associated with raised systolic blood pressure, raised glucose levels, and a previous diagnosis of diabetes. These associations were significant only in participants with no formal education. In this group the adjusted odds ratios for worse cognitive function were 1.18 (95% confidence interval [CI] 1.04-1.34) for each 10 mmHg increase in systolic blood pressure and 3.47 (1.14-10.6) for a previous diagnosis of diabetes. Odds ratios for the group with previous education were 0.99 (0.81-1.21) and 1.82 (0.48-6.92), respectively. Conclusion: The association between risk factors for cerebrovascular disease and cognitive impairment appears to be particularly strong in people with lower educational attainment.

Objective: This study compared medical history and findings on initial clinical examination in Native Americans diagnosed with possible or probable Alzheimer's disease (AD) at Native American satellite clinics of the University of Texas (UT) Southwestern Medical Center's Alzheimer's Disease Center with those of Whites diagnosed with probable AD at the UT Southwestern Medical Center's Alzheimer's Disease Clinic. Methods: The information reviewed was contained in the database of the UT Southwestern Alzheimer's Disease Center. Results: In relation to Whites, Native Americans had slightly but significantly greater age at onset of symptoms (71.7 vs. 69.6 years, t = −2.08, p = .04) and equivalent cognitive scores at evaluation (Mini-Mental State Exam score = 17.4 vs. 18.5, t = 0.98, p = .33), despite significantly lower educational level (11.4 vs. 13.4 years, t = 5.63, p < .001). Native Americans were more frequently depressed on examination (22.8% vs. 9.5%, χ2 = 12, p = .001) and reported diabetes, hypertension, and heart disease significantly more often than did Whites (p < .01 for all), but their survival time after AD diagnosis was similar to that of Whites despite these comorbidities. Conclusions: With the exception of a greater prevalence of depression and cardiovascular risk factors in Native Americans than in Whites, Native Americans had a course of illness similar to that of Whites.

Background: Older Puerto Ricans belong to two rapidly growing demographic groups known to have high rates of depression: the aging and Hispanic populations. Studies of depression in Puerto Ricans have primarily focused on the impact of demographic factors and health. This study expands previous research, examining the relationships between depression and social stressors, social support, and religiosity, for Puerto Rican primary care patients aged 50 and older. Patients: Participants included 303 Puerto Ricans from six primary care clinics in a northeastern city. Methods: Patients completed in-person interview in Spanish. The Composite International Diagnostic Interview indicated depressive disorders meeting DSM-IV criteria. Bivariate and multivariate relationships between depression and demographics, health, social stress and support, and religiosity were explored. Results: One fifth of participants met DSM-IV criteria for major depression or dysthymia. Participants with the lowest income, more recent migration, and poor subjective health were significantly more likely to be depressed. In addition, rates of depression increased steeply for patients caring for grandchildren and those with personal or family legal problems. Seeing few relatives each month and needing more instrumental, emotional, or financial support were also related to higher rates of depression. Unexpectedly, low objective illness severity correlated with increased depression, whereas religiosity and religious participation had no relationship to depression. Conclusions: The findings presented here indicate the potential for social stressors and inadequate supports to substantially increase the risk of depression in older Puerto Ricans in primary care settings. Further studies should explore incorporating these social risk factors into improved prevention, clinical detection, and culturally sensitive treatment of older depressed Puerto Ricans.

Background: We explored carer motivation for seeking participation for a relative in an Alzheimer's disease (AD) clinical drug trial, to assess impressions of the value of trial participation. We also surveyed the carers of patients who did not meet study entry screening criteria to see if our conduct of the screening visit was acceptable and ethical. Method: A retrospective questionnaire was sent to the carers of 36 randomized participants and 22 carers of patients who did not meet study entry screening criteria for an AD clinical treatment trial. Results: Twenty-nine (81%) of the trial participant carers and 15 (68%) of carers of the group who did not meet study entry criteria returned their questionnaires with sufficient information for analysis. The prime motivators in seeking trial participation were to help their relative feel better and live longer, to contribute to medical science, to improve the health of others, and the hope of a cure. Carers of both groups found research staff supportive and would recommend trial participatiion to others. Conclusions: Even though trial participation is onerous and patients were generally perceived by carers as not having improved, both the screening visit and participation in the trial itself were seen as positive experiences and the expectations of carers were met.

Vascular dementia (VaD) is a heterogeneous entity with a large clinicopathological spectrum. It has been classified and subclassified in many different ways. The difficulty in identifying the various subtypes is a problem in the diagnostic process. For clinical purposes, it is desirable to find subtypes of VaD that are homogeneous enough to allow meaningful comparisons across studies. This article presents candidates for such subtypes: poststroke dementia, subcortical VaD, and combined Alzheimer's disease and VaD (AD + VaD). The first two candidates are easy to identify. Poststroke dementia occurs with cognitive decline in close temporal relation to a transient ischemic attack. Subcortical VaD has a relatively homogeneous clinical picture for which detailed criteria are suggested. AD + VaD is more difficult to identify but is possible, sometimes with the aid of neuroimaging and/or biological markers.

Background: Dementia with Lewy bodies (DLB) is often associated with REM sleep behavior disorders (RBD) characterized, in contrast to the usual paralysis of REM sleep, by violent motor and verbal activity. Patients and Methods: The pharmacological management of RBD was investigated in three DLB patients treated with clonazepam, a benzodiazepine used as an antiepileptic, or donepezil, a cholinesterase inhibitor. Results: All three patients had marked improvement. The pharmacodynamic mechanisms underlying the efficacy of the two drugs might be due to facilitator effect on the pedunculopontine nucleus, a key structure in the physiology of REM sleep.

The increasing numbers of Asian and other immigrants in the United States have resulted in greater demands for research methodology sensitive to cross-cultural issues. A regional probability sample (n = 407) of Asian elderly immigrants of different nationalities (Chinese, Korean, Indian, Filipino, Vietnamese, or Japanese) residing in New York City was used to examine the reliability of the Geriatric Depression Scale (GDS). Using the 30-item GDS, about 40% of this representative sample of Asian elderly immigrants was considered to be depressed, indicating higher depression rates than in the previous studies of other Asian elderly samples in the US and in Asia. Results also showed that the 30-item GDS and 15-item GDS Short Forms were reliable measures to assess depression in community-dwelling Asian immigrant elders. Data strongly suggest that Asian elderly immigrants in the US are at risk of depression, indicating a need for the design of culturally sensitive mental health programs.

The objective of this study was to determine whether adult day service use was related to decreases in primary caregiving hours (i.e., the time caregivers spent on activities of daily living/instrumental activities of daily living and behavior problems for care recipients) and care recipient function for these domains. Three-month longitudinal data from the Adult Day Care Collaborative Study (N = 400) were used. Adult day service users reported greater decreases in hours spent on behavior problems when compared to nonusers, even after controlling for baseline differences between the two groups. In addition, adult day service users reported decreased frequency of behavior problems in their relatives who attended adult day programs. The findings suggest that adult day services, if used over time, are effective in restructuring caregiving time and may offer potential benefits not only to family caregivers but to community-residing older adults who have dementia as well.

The rapid advances in biomedical sciences have induced special moral and ethical attitudes, which ought to be taken into account. One of the most essential issues is the principles for participation in research of subjects with reduced decision-making capacity. We conducted a questionnaire survey among members of the research ethics committees in Sweden to find out their attitudes to a range of ethical issues related to research on subjects with Alzheimer's disease. One hundred thirty-six of those approached responded (66%), and 117 of the responses (56%) were considered substantially complete. There were 16 questions with fixed reply alternatives. Some central questions concerned the informed consent process. With a few exceptions, there were no significant differences in attitudes between the experts and laypersons, between persons of different ages, and between men and women. However, women and laypersons were in general keener to preserve the patient's integrity and the experts were more willing than the laypersons to allow participation of subjects with dementia in placebo-controlled trials.

“Mixed dementia” is traditionally defined as Alzheimer's disease with cerebrovascular disease (CVD). Because the risks of both neurodegenerative dementias and cerebrovascular disease increase with age, the mixed dementias are likely the most common. In practice, patients with mixed dementia are diagnosed by one of two routes: Either they have evidence of a neurodegenerative dementia and CVD at the outset, or, they have a classical neurodegenerative presentation but are found to have ischemic lesions by neuroimaging. These facts have implications for the development of evidence-based diagnostic criteria.

Background and Objectives: A variety of electroencephalogram (EEG) abnormalities may occur in schizophrenics who had a typical onset of the disorder in early adulthood. The purpose of this study was to investigate EEG findings in patients with late-onset schizophrenia (onset of illness between ages 40 and 60). Methods: Ten patients (one male, nine female, average age 52.8 years old) with late-onset schizophrenia underwent magnetic resonance imaging (MRI) of the brain and recording of quantitative EEG. Results: MRI results for seven of the subjects were within normal limits and the other three showed nonspecific changes. Quantitative analysis of EEG variables revealed that for eight of the subjects, absolute power and relative power for the four EEG frequency bands, overall mean frequency, mean frequency for each of the EEG frequency bands, and interhemispheric coherence values did not vary significantly from a normative database of age-matched normal subjects. Conclusions: Results obtained to some degree replicate the single previous EEG study of late-onset schizophrenia. These findings suggest that the neurophysiological etiology and mechanism of late-onset schizophrenia may differ from that of schizophrenia with a typical age of onset, and that brain abnormalities are not an inevitable accompaniment to late onset of schizophrenia.

Vascular involvement in Alzheimer disease (AD) is not necessarily coincident. Current evidence suggests the neuropathology of Alzheimer type of dementia comprises more than amyloid plaques and neurofibrillary tangles. At least a third of recognized AD cases may exhibit cerebrovascular pathology, which also constitutes distinct small vessel disease. Cerebral amyloid angiopathy, microvascular degeneration affecting the cerebral endothelium and smooth muscle cells, basal lamina alterations, hyalinosis, and fibrosis are frequently evident in AD. These changes may be accompanied by perivascular denervation that is causal in the cognitive decline of AD. In addition, amyloid β protein appears directly involved in the degeneration of both the larger perforating arterial vessels as well as cerebral capillaries, which represent the blood-brain barrier. The cerebrovascular pathology in AD also encompasses macro- and micro-infarctions, hemorrhages, lacunas, and ischemic white-matter changes. An interaction of both perivascular mediators and derived factors would perturb the brain vasculature. Peripheral vascular factors such as long-standing hypertension, atrial fibrillation, coronary or carotid artery disease, and diabetes mellitus are also apparent in AD. These factors would modify the cerebral circulation such that a sustained hypoperfusion or oligemia is impacted upon the aging processes to induce the characteristic pathology.

Objectives: To evaluate the impact of external memory devices on the efficacy of a package of internal mnemonic techniques. Participants wrote two types of lists during the study phase: (a) a list of study words and/or (b) a loci list. At recall, participants were not allowed to refer to either of the lists they had written during the study. Design: 2 × 2 factorial with writing study words (“write” or “not write”) and writing down a previously established loci list (“write” or “not write”) manipulated as between-participants variables. Participants: 68 community-dwelling adults 55 years of age and older who wished to improve their memory. Measurements: Free word recall. Results: There were statistically significant effects of writing the loci list, but not of writing the list of study words. Scores were higher when participants wrote the loci lists compared to when they did not. Conclusions: Use of external mnemonics may enhance the efficacy of internal mnemonics, even when the external mnemonic is not used at the time of recall.