Risk assessment of wandering behavior in mild dementia.

OBJECTIVE: This prospective longitudinal study aims to determine the risk factors of wandering-related adverse consequences in community-dwelling persons with mild dementia. These adverse consequences include negative outcomes of wandering (falls, fractures, and injuries) and eloping behavior. METHODS: We recruited 143 dyads of persons with mild dementia and their caregivers from a veteran's hospital and memory clinic in Florida. Wandering-related adverse consequences were measured using the Revised Algase Wandering Scale - Community Version. Variables such as personality (Big Five Inventory), behavioral response to stress, gait, and balance (Tinetti Gait and Balance), wayfinding ability (Wayfinding Effectiveness Scale), and neurocognitive abilities (attention, cognition, memory, language/verbal skills, and executive functioning) were also measured. Bivariate and logistic regression analyses were performed to assess the predictors of these wandering-related adverse consequences. RESULTS: A total of 49% of the study participants had falls, fractures, and injuries due to wandering behavior, and 43.7% demonstrated eloping behaviors. Persistent walking (OR = 2.6) and poor gait (OR = 0.9) were significant predictors of negative outcomes of wandering, while persistent walking (OR = 13.2) and passivity (OR = 2.55) predicted eloping behavior. However, there were no correlations between wandering-related adverse consequences and participants' characteristics (age, gender, race, ethnicity, and education), health status (Charlson comorbidity index), or neurocognitive abilities. CONCLUSION: Our results highlight the importance of identifying at-risk individuals so that effective interventions can be developed to reduce or prevent the adverse consequences of wandering.

Goals of care in advanced dementia: quality of life, dignity and comfort.

Prolongation of human lifespan is increasing the number of individuals suffering from Alzheimer's disease and other progressive dementia worldwide. There are about 5 million of these individuals in both United States and European Union and many more in other countries of the world (1). Because there is no curative treatment for these diseases, most individuals with dementia survive to an advanced stage of dementia at which time many of them require institutional care. Home care for individuals with advanced dementia and especially institutional care are very expensive and are becoming major public health problems. The cost of care for advanced dementia is often increased by the use of aggressive medical interventions that may not be in the best interest of the patient. Because advanced dementia is currently incurable, it should be considered a terminal illness, similar to terminal cancer. Therefore, palliative care may be the most appropriate strategy for management of advanced dementia (2). The goals of palliative care are maintenance of quality of life, dignity and comfort and the four articles in this special issue are addressing these goals. Enhancement of quality of life in dementia requires attention to three main domains: provision of meaningful activities, appropriate medical care, and treatment of behavioral symptoms (3). Individuals with advanced dementia may not be able to participate in many activity programs but they still may maintain some quality of life if they are provided care in a pleasant environment with constant presence of a caregiver. Simard describes a program, Namaste Care, which is specifically tailored for individuals with advanced dementia. This program requires neither major expenditure nor increased staffing and should be instituted in all facilities that care for individuals with advanced dementia. Maintaining functional status of individuals with advanced dementia is important because it improves their self esteem and facilitates provision of care. Van der Steen et al. present evidence that lower respiratory tract infection leads frequently but not always to functional decline. However, it is significant that the Dutch participants in this study were never hospitalized and always treated in a nursing home. Hospitalization leads to functional deterioration even in cognitively intact elderly individuals (4). In addition, treatment of lower respiratory infection is more effective when provided in a nursing home than when the resident is transferred to an acute care setting (5). It should also be considered that antibiotic treatment of lower respiratory tract infections in individuals with terminal dementia does not increase their comfort and lifespan (6). Dignity is an often invoked goal of care in dementia but it is often poorly defined and characterized. Holmerova et al. provide a detailed description of the concept of dignity and its application in dementia care. They also present two specific examples of problems encountered when individuals with advanced dementia are treated insensitively in an acute care setting. Dignity oriented care should treat everybody as an individual and provide care according to the goals of care determined before any crisis situation (7). Namaste Care is an example of care setting that respects individual's dignity until death; respecting "the spirit within". Tube feeding in individuals with advanced progressive dementia does not promote quality of life, dignity or comfort. Tube feeding deprives individuals from contact with the caregiver during hand feeding and from enjoyment of the taste of food. Tube feeding often requires use of restraints that decreases an individual's dignity and comfort. Despite the lack of beneficial effects and the burdens that the tube feeding imposes (8), it is still widely used in individuals with advanced dementia. Pang et al. compare the use of tube feeding in two different settings of dementia care, one in which tube feeding is not used and one in which everybody dies with some form of artificial feeding. She documents that the main reason for this difference is varying attitudes of medical staff and not different perceptions of best interest of the patient as expressed by the patient's relatives. It is hoped that this special issue will increase awareness of the medical community about appropriateness of palliative care for individuals with advanced dementia. Such care may not only provide better care for individuals with dementia and their families but may also save some health care resources (9). Palliative care is well accepted by many relatives of individuals with advanced dementia but not promoted by many health care professionals. We need to provide more education and research results for health care professionals to increase the use of palliative care in advanced dementia.

Comparing the ethical challenges of forgoing tube feeding in American and Hong Kong patients with advanced dementia.

OBJECTIVES: To develop a cross-cultural dialogue for enriching our understanding of how an ethical environment can be constructed in fostering tube-feeding decisions in patients with advanced dementia (AD). DESIGN AND DATA SOURCE: Drawing on the findings of two prospective case studies conducted in Boston and Hong Kong, this paper compares the decision-making patterns of forgoing tube feeding for AD patients and their emergent ethical dilemmas typified in a special dementia care unit in Boston (BCU) and a long-term care unit in Hong Kong (HKCU). FINDINGS: Differences in forgoing tube feeding decision are delineated in the two places. No-tube-feeding practice was sustained in BCU in two ways: advance decision-making with respect paid to the patient's wishes and advance proxy decision-making focused on patient comfort. With life preservation as the prevailing value in the Hong Kong medical system, only strong family request coupled with medical evidence of patient's ability to continue hand-feeding that tube feeding would be discontinued. All patients died with some form of artificial feeding. CONCLUSION: A paradigm shift of values underpinning the practice of forgoing tube feeding in the context of palliative care is observed in three aspects. First, the emphasis on prognostication based on biomedical markers in predicting the length of survival is shifted to a focus on the "diagnosis of dying". Second, the overriding concern in conventional medical practice with preserving life is shifting to an overriding concern of "what is best for the patient." Third, in the last days of life, the conventional approach of "trying to do everything for the patient" had shifted from a technological to a relational one. Palliative measures for relieving discomfort and providing a peaceful and dignified environment in which the patient could die are the primary concern. Although the predominant medical culture in Hong Kong is biomedical, voices from the patients and family members challenge this conventional practice, and suggest that the alternative model may be a better choice.

Assessment of Diagnostics Tools for Sarcopenia Severity Using the Item Response Theory (IRT).

OBJECTIVE: To use the item response theory (IRT) methods to examine the degree to which the four selected tools reflect sarcopenia and to arrange them according to their ability to estimate sarcopenia severity. DESIGN: A cross-sectional study aimed at verifying the possibilities of using diagnostic tools for sarcopenia. SETTING AND PARTICIPANTS: The study included residents living in an assisted living unit at the Senior Centre in Blansko (South Moravia, Czech Republic) (n=77). Sarcopenia was estimated according to the proposals of the European Working Group on Sarcopenia in Older People (EWGSOP) using calf circumference, the EWGSOP algorithm, hand grip strength, and the Short Physical Performance Battery (SPPB). RESULTS: The results from the IRT model showed that these four methods indicate strong unidimensionality so that they measure the same latent variable. The methods ranked according to the discrimination level ranging from high to low discrimination where the calf circumference was the most discriminatory (Hi = 0.86) and the SPPB together with hand grip strength were the least discriminatory (both Hi = 0.44). CONCLUSION: We are recommending to identify mild sarcopenia by SPPB or hand grip strength, moderate sarcopenia by the EWGSOP algorithm and severe sarcopenia by the calf circumference.

Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration.

BACKGROUND: Caregiver exhaustion is a frequent consequence of sleep disturbance and rest-activity rhythm disruption that occurs in dementia. This exhaustion is the causal factor most frequently cited by caregivers in making the decision to institutionalize patients with dementia. Recent studies have implicated dysfunction of the circadian pacemaker in the etiology of these disturbances in dementia. METHODS: We studied the activity and core-body temperature rhythms in a cohort of 38 male patients with a clinical diagnosis of probable Alzheimer disease (AD) approximately 2 years before death. These patients were later given a confirmed diagnosis of AD (n = 23), frontotemporal degeneration (FTD) (n = 9), or diffuse Lewy body disease (DLB) with mixed AD or FTD pathologies (n = 6) after autopsy and neuropathological examination. Physiological rhythms of patients with AD and FTD were then compared with a group of normal, elderly men (n = 8) from the community. RESULTS: Alzheimer patients showed increased nocturnal activity and a significant phase-delay in their rhythms of core-body temperature and activity compared with patients with FTD and controls. The activity rhythm of FTD patients was highly fragmented and phase-advanced in comparison with controls and apparently uncoupled from the rhythm of core-body temperature. CONCLUSIONS: Patients with AD and patients with FTD show different disturbances in their rhythms of activity and temperature compared with each other and with normal elderly patients.

Development of reversible hypertension during disulfiram therapy.

An alcoholic patient had a gradual increase of BP while he was treated with disulfiram. The BP returned to normal after the disulfiram was withdrawn. Increased BP should be considered a possible side effect of long-term disulfiram therapy, especially in the presence of alcohol-induced liver damage.

Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia.

Sleep disruption and other circadian rhythm disturbances are frequently seen in dementia patients. In this study, we examined the suprachiasmatic nucleus (SCN), the putative site of the hypothalamic circadian pacemaker, to determine the nature and degree of pathologic changes caused by severe dementia. Neuropathologic examination indicated that among 30 patients with a clinical history of severe dementia, 22 had Braak and Braak stage V-VI Alzheimer disease, 3 had combined Alzheimer and Parkinson disease, 3 had Pick disease and 2 had severe hippocampal sclerosis. Comparisons were made with a control group composed of 13 age-matched patients with no clinical or pathological evidence of dementia or other CNS disorders. To determine the pathologic involvement within the SCN, human hypothalami were stained with: Nissl, Bielchowsky silver, thioflavin S and specific antibodies directed against vasopressin (VP), neurotensin (NT), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), beta-amyloid (B/A4) and glial fibrillary acidic protein (GFAP). Pathologic damage was primarily limited to neuronal loss and neurofibrillary tangle formation. Only rare diffuse plaques were noted. The pathologic changes within the SCN were less severe than in the other brain regions. Morphometric analysis was accomplished using a stereological approach to sample the average total number of positively stained neurons and astrocytes in 10 different 0.1mm2 microscopic fields in the dorsal subdivision of the SCN. Patients with Alzheimer disease exhibited a significant decrease in vasopressin (9.75 vs 16.7, p < 0.001) and neurotensin (6.82 vs 9.63, p < 0.002) neurons, as well as a corresponding increase in the GFAP-stained astrocyte/Nissl-stained neuron ratio (0.54 vs 0.10, p < 0.009). These studies provide evidence that both vasopressin and neurotensin neurons are lost in Alzheimer disease, and that the astrocyte/neuron ratio is a reliable indicator of disease-related pathology within the SCN. Taken collectively, our data support the hypothesis that damage to the SCN may be an underlying anatomical substrate for the clinically observed changes in circadian rhythmicity that have been observed in Alzheimer patients.

Cholinesterase activity in plasma, erythrocytes, and cerebrospinal fluid of patients with dementia of the Alzheimer type.

Cholinesterases, including pseudocholinesterase (BChE) of human plasma and acetylcholinesterase (AChE) of erythrocytes and cerebrospinal fluid (CSF), have been considered as possible markers in dementia of the Alzheimer type (DAT). Reported data, however, are widely varied, and no significant pattern emerges when total enzyme activity is assayed. In the present studies, we have reexamined the relationship of ChE activities in DAT and control patients. ChE activity was measured in plasma, erythrocytes, and CSF from DAT patients and compared with normal controls as well as with samples from patients with a diagnosis other than DAT. Early age onset (presenile) and late age onset (senile) DAT were also compared. No significant differences in total enzyme activity were found in any of the comparisons. Calculations of AChE/BChE ratios in CSF also provided no significant indication of any changes in ChE activities in DAT. It is suggested that measurements of total AChE or BChE activity in these biological materials do not provide a useful index of alterations in central cholinergic function in patients with DAT.

Cerebrospinal fluid levels of angiotensin-converting enzyme, acetylcholinesterase, and dopamine metabolites in dementia associated with Alzheimer's disease and Parkinson's disease: a correlative study.

Mean levels of the two hydrolases angiotensin-converting enzyme (ACE) and acetylcholinesterase (AChE), the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and total protein concentration were examined in cerebrospinal fluid (CSF) samples from a group of patients with dementia of the Alzheimer's type, a group of comparably demented patients with Parkinson's disease, and a neurologically healthy elderly control group. Both pathological groups exhibited a significant decrease in the mean levels of ACE activity and DOPAC per milliliter and were distinguishable from one another based on mean CSH HVA levels. Unlike the Parkinson's disease group, whose mean concentration of HVA was lower than, but not significantly different from that of the control group, the mean HVA concentration of the Alzheimer's disease group was significantly elevated. In contrast, comparisons of the mean CSF AChE activity (expressed per milliliter or per milligram of protein) and CSF total protein concentration did not reveal significant differences for any of the groups. Independent of CSF protein concentration, ACE activity per milliliter exhibited a positive correlation with AChE activity per milliliter within the control and Parkinson's disease groups, whereas a statistically significant correlation for these CSF hydrolases was not observed within the Alzheimer's disease group. Thus, the CSF profiles for patients with mild dementias associated with Alzheimer's or Parkinson's disease differed by at least two neurochemical criteria. Based on the levels of ACE activity, DOPAC, and HVA per milliliter of CSF, two discriminant functions were derived and resulted in the correct classification of 71% of all subjects (n = 38) into Alzheimer's disease, Parkinson's disease, and neurologically healthy control groups.

Involvement of free radicals in dementia of the Alzheimer type: a hypothesis.

We propose that increased formation of oxygen-derived free radicals, such as the superoxide and hydroxyl species, may be responsible for progressive neural degeneration in dementia of the Alzheimer type (DAT). Several processes increase free radical formation and some of them (e.g., brain trauma, aging) are risk factors for DAT. There is some evidence for increased free radical formation in Down's syndrome which is associated with development of DAT pathology. Free radicals alone may induce cell death by damaging lipids or proteins while reactions between free radicals and neurotransmitters may lead to formation of endogenous neurotoxin(s). Recently, we have demonstrated that partial oxidation of serotonin by exposure to hydroxyl radicals results in formation of a novel neurotoxin, tryptamine-4,5-dione. Elucidation of the role of free radicals in DAT could open new avenues to prevention and treatment of this disease.

Epinephrine-induced cyclic AMP production in skin fibroblasts from patients with dementia of Alzheimer type and controls.

Skin biopsies were obtained from six patients with dementia of Alzheimer type (DAT) and from three hospitalized age matched controls. Fibroblasts from these biopsies were grown in culture and compared for their growth characteristics and sensitivity to epinephrine with four cultures from age matched healthy individuals. The growth characteristics were similar in all three groups. The basal levels of cyclic AMP and the epinephrine-induced increase of cyclic AMP levels were also similar in control and DAT cells.

Circadian locomotor activity and core-body temperature rhythms in Alzheimer's disease.

Sleep-wake cycle disturbances suggest that circadian rhythms may be disrupted in patients with Alzheimer's disease (AD). In this study, we examined the circadian rhythms of core-body temperature and locomotor activity in 28 patients with probable AD and 10 healthy controls. AD patients had higher percent nocturnal activity than controls, corresponding to the clinical picture of fragmented sleep. The amplitude of the activity cycle in the AD patients was lower than that of controls and the acrophase of this cycle in AD patients was 4.5 h later. There was no difference in the amplitude of the core-body temperature circadian rhythm, but AD patients had delayed temperature acrophases. A subgroup of AD patients with large mean time differences between the acrophases of their activity and temperature cycles had lower temperature amplitudes and greater activity during the night. These findings suggest that a subgroup of AD patients with impaired endogenous pacemaker function may have a diminished capacity to synchronize the rhythm of core-body temperature with the circadian cycle of rest-activity. This circadian rhythm dysfunction may partly explain the fragmented nocturnal sleep exhibited by these patients.

Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease.

OBJECTIVE: The authors tested the hypothesis that evening bright light pulses would improve sleep-wake patterns and reduce agitation in patients with Alzheimer's disease who have severe sundowning (a syndrome of recurring confusion and increased agitation in the late afternoon or early evening) and sleep disorders. METHOD: Ten inpatients with Alzheimer's disease on a research ward of a veterans' hospital were studied in an open clinical trial. All patients had sundowning behavior and sleep disturbances. After a week of baseline measurements, patients received 2 hours/day of exposure to bright light between 7:00 p.m. and 9:00 p.m. for 1 week. During the baseline week, the treatment week, and a posttreatment week, patients were rated by nurses for agitation, sleep-wake patterns, use of restraints, and use of prescribed-as-needed medication. On the last 2 days of each week, patients wore activity monitors. Activity counts were analyzed for circadian rhythmicity. RESULTS: Clinical ratings of sleep-wakefulness on the evening nursing shift improved with light treatment in eight of the 10 patients. The proportion of total daily activity occurring during the nighttime decreased during the light-treatment week. The relative amplitude of the circadian locomotor activity rhythm, a measure of its stability, increased during the light-treatment week. More severe sundowning at baseline predicted greater clinical improvement. CONCLUSIONS: Evening bright light pulses may ameliorate sleep-wake cycle disturbances in some patients with Alzheimer's disease. This effect may be mediated through a chronobiological mechanism.

Sundowning and circadian rhythms in Alzheimer's disease.

OBJECTIVE: The goal of this study was to determine changes of circadian rhythms induced by Alzheimer's disease and to explore relationships among rhythm disturbances, sundowning, and sleep disturbances in patients with Alzheimer's disease. "Sundowning" is the occurrence or exacerbation of behavioral symptoms of Alzheimer's disease in the afternoon and evening. METHOD: Circadian rhythms of core body temperature and motor activity were measured in 25 patients with diagnoses of probable Alzheimer's disease and in nine healthy individuals. The subjects with Alzheimer's disease were divided according to the occurrence of sundowning as determined by staff reports. RESULTS: The subjects with Alzheimer's disease had less diurnal motor activity, a higher percentage of nocturnal activity, lower interdaily stability of motor activity, and a later activity acrophase (time of peak) than did the healthy individuals. They also had a higher mesor (fitted mean) temperature, higher amplitude of the fitted cosine temperature curve, and later temperature acrophase than did the healthy subjects. The severity of sundowning was associated with later acrophase of temperature, less correlation of circadian temperature rhythm with a 24-hour cycle, and lower amplitude of temperature curve. CONCLUSIONS: These data indicate that Alzheimer's disease causes disturbances of circadian rhythms and that sundowning is related to a phase delay of body temperature caused by Alzheimer's disease.

Persistent vegetative state in Alzheimer disease. Does it exist?

OBJECTIVE: To determine if the published criteria for diagnosis of the persistent vegetative state could be applied to patients suffering from Alzheimer disease. DESIGN AND METHODS: Eighty-eight institutionalized patients with a diagnosis of possible or probable Alzheimer disease were evaluated for the presence of persistent vegetative state. Initial screening excluded patients who were able to do any of the following: feed themselves, respond to command, walk, or maintain continence of bowel and bladder. A sample of 12 of 28 patients unable to perform any of these functions was examined independently by 3 of us. RESULTS: During the first examination, 2 patients were diagnosed as being in a vegetative state by 2 of us and 3 additional patients by 1 of us. One of us did not diagnose any patient as being in a vegetative state. A second evaluation of the same patients was performed 2 months later, after holding a consensus meeting to standardize the evaluation procedure. During the second evaluation, the vegetative state was diagnosed in 6 patients but only by 1 of us. CONCLUSION: The diagnostic disagreement between the neurologists indicate that Alzheimer disease may only rarely progress to the persistent vegetative state.

Serotonin and 5-hydroxyindoleacetic acid in CSF. Difference in Parkinson's disease and dementia of the Alzheimer's type.

Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the sixth, 13th, and 20th milliliters of CSF in patients with dementia of the Alzheimer's type (DAT) and Parkinson's disease (PD), and in an aliquot of CSF in controls. In patients with PD there was a positive correlation between 5-HT and 5-HIAA levels in the 20th milliliter of CSF, while in patients with DAT there was a negative correlation of these levels in this CSF fraction. In patients with the senile form of DAT the 5-HIAA levels in the 20th milliliter of CSF were higher than in patients with PD. These results indicate differential involvement of the serotoninergic system in DAT and PD, and may lead to the development of a chemical marker for DAT.

Serotoninergic system in dementia of the Alzheimer type. Abnormal forms of 5-hydroxytryptophan and serotonin in cerebrospinal fluid.

Serotonin (5-HT), its precursor 5-hydroxytryptophan (5-HTP), and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in the cerebrospinal fluid (CSF) of 14 patients with dementia of the Alzheimer type (DAT) and in nine controls by high-performance liquid chromatography with a novel multisensor coulometric detection system. Concentrations of both 5-HT and 5-HIAA detected by this system were lower than the concentrations obtained using conventional amperometric detection. This difference was caused by coelution of compounds that could be resolved from 5-HT and 5-HIAA by the multisensor coulometric system. One of the coelution compounds, observed in DAT but not in control CSF, behaved like a partially oxidized 5-HT. A compound behaving like partially oxidized 5-HTP was also observed in DAT CSF. Concentrations of 5-HTP, 5-HT, and 5-HIAA were lower in DAT CSF than in a corresponding fraction of control CSF. These results indicate involvement of the serotoninergic system in DAT and might lead to development of a diagnostic test for DAT.

Parkinson's disease. The possible relationship of laterality to dementia and neurochemical findings.

We examined the relationship of disease laterality to neuropsychological and neurochemical features in patients with idiopathic Parkinson's disease (PD). We tested patients with PD, patients with Alzheimer's type of senile dementia, and a control group neuropsychologically, and we determined their CSF levels of homovanillic acid, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindolacetic acid, serotonin, and acetylcholinesterase. The patients with PD were divided into two groups depending on the side of the body with greater disease involvement. Both parkinsonian groups, those more affected on the left (group L) and those more affected on the right (group R), were otherwise similar in all other clinical and historical features. Group L patients showed greater neuropsychological impairments than group R patients. Group L also had significantly higher CSF levels of homovanillic acid and acetylcholinesterase than group R. These findings of neuropsychological and neurochemical differences between groups L and R suggest functional or anatomic asymmetries of dopaminergic systems in the CNS.

Brain gangliosides in dementia of the Alzheimer type.

Gangliosides GM1, GD1a, GD1b, and GT1b were measured in nine brain regions of five patients, clinically and neuropathologically diagnosed as having dementia of the Alzheimer type (DAT), and of three control patients. Analysis of variance revealed that mean concentrations of all gangliosides analyzed were significantly lower in DAT than in control brains. The areas affected in DAT included the nucleus basalis, and entorhinal, posterior cingulate, visual, and prefrontal cortices. A significant interaction between ganglioside type and brain area indicated unequal ganglioside concentrations. Individual gangliosides had significantly different concentrations in the hippocampal, entorhinal, posterior cingulate, visual, and prefrontal cortices. Analysis of ratios of "a"-ganglioside (GM1 and GD1a) and "b"-ganglioside (GD1b and GT1b) subtypes indicated that DAT preferentially affected "b"-gangliosides. Ganglioside concentrations in nucleus basalis did not correlate with age at disease onset, age at death, or postmortem interval. Changes in gangliosides, observed in this study, were not correlated with classic DAT neuropathology.

Age-related changes of cyclic nucleotide levels in rat brain regions.

Cyclic AMP and cyclic GMP levels were measured in seven brain areas of rats 4-30 months old. In several brain areas cyclic nucleotides were higher in 4-month-old rats than in rats 12 months old or older. On the other hand, in the hypothalamus cyclic GMP levels were decreased only in 30-month-old rats, a pattern of onset similar to that of senile deterioration.