Alzheimer's disease is characterized by loss of cells and synapses in specific neural systems. The development of more effective therapies will depend on understanding the relationships between this pathology and the cognitive and behavioral impairments. In this review, focusing primarily on work in our laboratory, we will examine both classic and neuropeptide neurotransmitter systems and will discuss conceptual and methodological problems in relating clinical and biological measures.

Medications with anticholinergic properties, when taken at therapeutic doses, are known to adversely affect memory functioning in young adults and the elderly. However, their impact at lower doses in geriatric persons has been less thoroughly studied. We investigated the impact of a single 2-mg dose of trihexyphenidyl on memory functioning in 20 healthy elderly subjects using a within-subjects, double-blind comparison with a placebo. Memory functioning was evaluated using subtests of the Wechsler Memory Scale. Subjects also rated the perceived impact of medication on their performance following memory testing.

Results indicated that the single 2-mg dose of trihexyphenidyl produced impaired performance on measures of immediate and half-hour delayed recall of complex verbal and visual material when compared to the placebo condition. However, differences were not found on several other memory measures, including general orientation, attention-concentration, and learning of word associations. The significance of these selective memory deficits and suggestions regarding future research are discussed.

Normative data were collected in a study population of 150 randomly selected elderly subjects. Using the SIDAM (Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, multi-infarct dementia, and dementias of other etiology according to DSM-III-R and ICD-10), both the dimensional and the categorical aspects of dementia and “mild cognitive impairment” are considered. With the SIDAM score (SISCO) [range 0 (minimum)-55 (maximum, no cognitive impairment)] and the SIDAM Mini-Mental State Examination (MMSE) (range 0–30), appropriate cutoffs for the category of DSM-III-R and ICD-10 dementia and “mild cognitive impairment” were defined. MMSE scores of 0–22 were found to be indicative of DSM-III-R and ICD-10 dementia. For “mild cognitive impairment,” MMSE scores ranged from 23–27 according to a DSM-III-R definition (ICD-10: 23–28). An MMSE score of 22 or less was found to differentiate between DSM-III-R/ICD-10 dementia and “mild cognitive impairment,” with a specificity of 92% (ICD-10: 95.6) and a sensitivity of 96% (ICD-10: 96%). With the SIDAM-based DSM-III-R/ICD-10 diagnoses of dementia as the criterion, the SISCO was 97.3% specific (ICD-10: 99%) and 94% sensitive (ICD-10: 94%) in detecting dementia. A SISCO of 0–33 was highly indicative of DSM-III-R and ICD-10 dementia. For “mild cognitive impairment,” a SISCO between 34–47 (ICD-10: 34–51) was found. The SISCO covers a broader range of cognitive functions that the MMSE and is more useful in detecting even very mild cognitive decline. Furthermore, the newly defined category of “mild cognitive impairment” could be validated successfully by means of GDS Stages 2–3 and CDR Stage 0.5. These findings confirm the value of the SIDAM as a short diagnostic instrument for measurement and diagnosis of dementia and “mild cognitive impairment.”

Diagnosis of dementia needs to be complemented by precise determination of disease severity across the broad spectrum of disease progression. The Mini-Mental State Exam (MMS), the Activities-of-Daily-Living assessment (ADL) and the Clinical Dementia Rating scale (CDR) were modified for direct comparability and administred to 112 outpatients and 45 nursing home residents with a range of dementia severity from mild to profound. The scales showed the highest correlations for the probable Alzheimer's disease patient group (62) (Global Assessment of Dementia; GAD vs. ADL: r = 0.91; Extended Mini-Mental Assessment; EMA vs. GAD: r = 0.91; ADL vs. EMA: r = 0.86). For these patients, scores on the individual scales tended to be similar. Disparity among the three scores for individual cases was associated with the presence of comorbidities. The high correlations and correspondence among these scales demonstrate their reliability, validity, and utility in the assessment of dementia severity. The use of an average of these measures, with their increased precision, may give a more accurate indication of dementia severity over a broader range of impairment.

One hundred and sixty-eight elderly subjects in a geriatric hospital and the adjoining nursing home were examined in a study of relationships among the items of Hasegawa's dementia scale. A three-dimensional model using multivariate analysis demonstrated the relationships among items. The results led to the identification of six clinical groups determined by the presence of stroke and the score on the dementia scale. Nonstroke subjects of middle intellectual level had disturbances of memory and orientation. This group fell into two categories during the course of a five-year follow-up study: severe dementia and intellectual deterioration. Retrospective multivariate analysis results suggested that features characteristic of the severe intellectual deterioration group were earlier disturbances of orientation and distant memory. This statistical method used only objective clinical data in order to avoid subjective and, often, baised judgements.

Agitated behaviors in the nursing home pose a major problem for caregivers. Our data showed that the three syndromes of agitation—aggressive behaviors, physically nonaggressive behaviors, and verbally agitated behaviors—are differentially related to medical and psychosocial variables. Physically nonaggressive behaviors may be adaptive for a resident who presents a deteriorated stage of dementia, since these behaviors offer stimulation and exercise. Verbally agitated behaviors may be a form of help-seeking behaviors for residents with physical disease and depressed affect. Aggressive behaviors are those least understood, although these behaviors correlate with advanced stages of dementia and with poor interpersonal relationships. These findings should be a basis for further studies, with the ultimate goal being improved care for agitated elderly persons.

Dementia patients' and normal elderlies' recognition of familiar, ordinary emotional and facial expressions was tested. In three conditions subjects were required to name the emotions depicted in pictures and to produce them while presented with the verbal labels of the expressions. The dementia patients' best performance occured when they had access to the verbal labels while viewing the pictures. The major deficiency in facial recognition was found to be dysnomia related. Findings of this study suggest that the connection between the gnostic units of expression and the gnostic units of verbal labeling is not impaired significantly among the dementia patients.

New findings on cognitive aging show that decline in brain functions is not part of a general decline of functioning in old age. We know now that with increasing age there is a differentiation of cognitive functions into two independent dimensions (fluid and crystallized functions).

This two-dimensional model allows a more precise description of the cognitive aging process and of pathological changes. While crystallized cognitive abilities can be improved by training till late in life, fluid cognitive functions are subject to a progressive decrease starting as early as age 30, becoming most evident in cases of organic mental disorders.

Thus, pathological aging is not necessarily accompanied by global loss of functions. Different abilities undergo changes in different ways, a fact taken into consideration by modern methods of psychometric evaluation. Beyond the aging processes mentioned previously, cognitive and behavioral changes in the elderly may be considered to be early indicators of organic mental disorders. The Nuremberg Self-Evaluation List seems to be a promising approach to diagnosis.

This paper addresses the questions of whether depression compromises cognition in the elderly and whether discernable patterns of cognitive performances could be differentiated between patients with severe depression and those with organic dementia. Published data on geriatric depression and cognitive functioning are divided in demonstrating a depression effect. Further examination and external validation by new data show that the depression effect on discrete cognitive tasks is (1) small, and (2) sensitive to the confounding of sampling and task variables. Future research must take these factors into account. Patterns of cognitive functioning in depression and dementia are different and can be differentiated using a variety of measures. This review finds the term pseudodementia inappropriate and misleading and recommends that it be abandoned.

Nimodipine is a calcium antagonist which improves learning and memory in brain-lesioned or aged animals (LeVere & Sandin, 1989; Schuurman & Traber, 1989). It also accelerates the recovery of experimentally damaged sciatic nerves (van der Zee et al., 1987) and reduces age-associated gait abnormalities in aging rats (Schuurman et al., 1987). Selective action on cerebral vessels has also been proven. Vasoconstriction was prevented or reduced with nimodipine under experimental conditions (Toward, 1981) and cerebral blood flow could be increased (Kazda et al., 1982). The drug has been tested in subarachnoid hemorrhage, stroke, severe head injury, cerebral resuscitation after cardiac arrest, impaired brain function in old age, and dementia. Methodological aspects of clinical studies with this agent are examined in this paper.

This article discusses the role of some pathogenetical factors in the main morphological variants of vascular dementia and their correlation with certain clinical parameters. On the basis of computer-tomographical (CT) studies of 62 patients with dementia, it was possible to distinguish three groups of patients, according to the type of parenchymatous brain lesions: (1) 14 patients with “pure” leukoaraiosis (LA); (2) 23 patients with ischemic foci (IF), and (3) 25 patients with a combination of LA and IF. A comparative study of these groups confirmed the concept that in the development of LA and dementia related to it, a special role is being attributed to such factors as arterial hypertension and aging.

A prospective pilot study compared the Neurobehavioral Cognituve Status Examination (NCSE) to the Folstein Mini-Mental State Examination (MMSE) to determine the usefulness of the NCSE as a cognitive screen in a geriatric inpatient population. All patients directly admitted to the geriatric evaluation and treatment unit (GETU) of a university teaching hospital over a two-and-a-half-month period were eligible for the study, in which 42% participated, Within 72 hours of admission, patients were given the MMSE and the NCSE in a nonrandom order by a trained psychologist and a structured interview by a psychiatrist. The ability of the NCSE to detect global cognitive impairment was compared to the MMSE and psychiatrist's assessment. Differences in sensitivity were examined by discordant pair analysis. The psychiatrist's determination of the presence of cognitive impairment was used as the criterion standard. Comparison of the MMSE and NCSE, respectively, revealed the following: sensitivity 83% versus 100%; specificity 78% versus 11%; positive predictive value 83% versus 43%; and negative predictive value 78% versus 100%. Seven patients who were cognitively impaired by the NCSE were not impaired by the MMSE (p < 0.05 by discordant pair analysis). The time of administration for the two tests was significantly shorter for the MMSE (14.75 ± 5.7 minutes) than for the NCSE (38.9 ± 12.9 minutes). The NCSE was found to be more sensitive than the MMSE in detecting cognitive impairment among geriatric inpatients, but its specificity and positive predictive values were lower. Beyond this pilot study, additional work examining the utility of the NCSE in other geriatric settings and for different purpose (e.g., as part of comprehensive assessment) needs to be performed.

A nutritional study of 100 patients enrolled in an active geriatric outpatient teaching program was conducted to document the clinical impression of weight loss in Alzheimer's disease. All new patients were asked to complete a questionnaire on nutrition. Patients were evaluated by a geriatrician, then categorized using DSM-III and NINCDS-ADRDA criteria. There were 34 Alzheimer patients and 60 nondemented patients with an average weight of 56.2 kgs and 66.1 kgs, respectively (p < .002). Of the Alzheimer group, 44% reported weight loss in the past five years compared with 37% of the nondemented group, despite a concomitant increase in food intake in 35% versus 7%, respectively. On a one-year follow-up, 92% of Alzheimer patients lost weight, whereas 57% of the nondemented patients actually gained weight. The increase in reported food intake, with a significant concomitant weight loss, raises some challenging questions as to the existence of a hypermetabolic state in Alzheimer's disease.

Stake's concept of Responsive Evaluation is applied in evaluating the chain of psychogeriatric services of a general psychiatric hospital. Central to the approach presented are methodological considerations in describing individual treatment courses in their objective and subjective features. This can only be accomplished by establishing multidimensional strategies, incorporating biological, mental, psychological, and sociocultural aspects.

Treatment of dementia costs billions of dollars in long-term care and community services every year. Dementia also burdens the acute care system and may contribute to financial problems for hospitals serving large numbers of demented elderly. In a specialized geriatric medical unit devoted to acute care of the frail elderly, Alzheimer's disease and vascular and mixed dementias afflicted 63% of inpatients and were associated with excess consumption of nursing resources, complications of treatment, nosocomial infections, lengthy hospitalizations, and financial losses to the hospital. Due in part to the effects of dementia on mobility, continence, and nutrition, demented patients suffered more frequently from life-threatening infections, sepsis, iatrogenic disease, and prolonged hospital stays. Hospital losses were 75% higher for demented patients than for nondemented patients.

Dementia affected the majority of acute care patients in this study. However, it was rarely coded as an admitting diagnosis, even though it may have been the proximate cause of the medical morbidity which led to the acute hospitalization. In addition, despite the significant impact of dementia on the hospital course and costs, it was a factor in hospital reimbursement in less than one third of cases. The results indicate that dementia was not considered to be an acute diagnosis, nor was it recognized as a complex medical illness. The impact of dementia on acute hospitalization, including the mechanisms by which dementia prolongs the hospital stay, requires further investigation.

The frameworks of Erikson (1963) and Butler (1963) were used to design this descriptive study that investigated the relationships among life review, ego integrity, and death anxiety in older adults. Three hypotheses were proposed: (a) the greater the life review, the higher the ego integrity; (b) the greater the life review, the lower the death anxiety; (c) the higher the ego integrity, the lower the death anxiety. The sample consisted of 115 female and male volunteers between the ages of 65 and 93. The participants filled out the Life Review Questionnaire, Adult Ego Development Scale, Death Anxiety Scale, Death Preparation Scale, and a Personal Information Sheet. Life review, while not positively correlated with ego integrity, was found to have a negative correlation with death anxiety. Also, religious subjects were found to be more prepared for death than those who did not practice. Implications for therapy and future research are discussed, as well.

This study examined the underlying variables of selected reminiscing processes to determine those that contributed to well-being. Two hundred and forty subjects randomly selected from nursing homes and high-rises participated in one of 10 different reminiscing modalities for eight weeks. Measures of life satisfaction (LSI-A), psychological well being (ABS), selfesteem (SES), and depression (BDI) were given pre- and postintervention to determine the most therapeutic treatment modalities. Results showed the most therapeutic way to reminisce was through a structured, evaluative life review performed on an individual basis. Thus, three variables contributed to successful reminiscing: individuality (one-to-one reminiscing), evaluation (a personal valuing of events), and structure (covering the whole life span).

A scientific information base is developing which focuses on understanding and managing behavior problems in geriatric populations, especially those with dementing illnesses such as Alzheimer's disease. Many of these behavior problems occur in long-term care settings, which have a high prevalence of residents exhibiting emotional and behavioral disorders, often secondary to psychiatric illness. Prior to beginning treatment, behavior disorders must be systematically evaluated and understood to insure optimum care planning. One approach to effectively treating these disorders is to first separate them into two categories: those not amenable to psychotherapeutic medication treatment (nonpsychiatric disorders) and those that are amenable (psychiatric disorders). Specific nonpharmacological treatments may benefit those nonpsychiatric behavioral disorders and include behavioral and environmental paradigms. The psychiatric disorders, especially aggression and assaultive behavior, may be treated beneficially using a variety of psychopharmacological agents, including antianxiety agents, neuroleptics, carbamazapine, ß-blockers, and lithium. The most effective approach toward treating the psychiatric behavior disorders often combines both medication and nonmedication strategies.

Patients (n = 191) living in four comparable somaic nursing homes (NH) (nursing homes for physical illness) were studied in order to evaluate dementia syndromes. Dementia and symptoms of depressed mood occurred frequently (72% and 63%, respectively). Dementia was often undiagnosed at admittance. Neither the length of time spent in institutions, nor marital status, age, or sex seemed to be of more than minor importance to the prevalence of dementia syndromes. Concerning functional impairment, convergence of findings across the societies studied indicates that psychiatric symptoms and psychopathology are intrinsic parts of long-term care of the elderly.

Chronic cerevrovascular disturbances of the aged are characterized by a decline of attention. When these patients undergo pharmacological treatment, it is very difficult to distinguish between a direct benefit and/or a secondary effect on memory resulting from attention improvement. In our study we have proposed and evaluated a new method for identifying the different components of therapeutic efficacy on memory and attention in chronic cerebrovascular patients. This method is based on the use of the Randt Memory Test, traditional scores of memory efficiency (Acquisition, Recall, and a combined index), and the RMT three-factor scores derived from a structural model of memory functioning. The three scores have been called Encoding and Organization, Cognitive Efficiency, and Attention Efficiency. Participants were 96 selected chronic cerebrovascular patients treated in a double-blind study for 12 weeks with dihydroergocristine versus placebo. While changes in both acquisition and recall scores were related to the treatment, only changes of the Encoding and Organization factor scores were systematically related to therapy. Changes in Attention Efficiency were positively related to therapy only in proportion to the degree of cerebrovascular impairment.