Primary Degenerative Dementia Research Articles

The Hachinski Ischaemic Score: A reevaluation

AbstractThe Hachinski Ischaemic Score (HIS) was first introduced in 1975 as a clinical scale intended to differentiate cases of dementia resulting from multiple strokes (multi‐infarct dementia) from those with primary degenerative dementias. Its conceptual basis rests on the view that vascular dementia is the result of strokes, not of general atherosclerosis or ischaemia. This article critically examines the psychometric properties of the scale. Reliability studies are singularly lacking, and studies of its validity have produced inconsistent findings. Furthermore, there has been a change of views regarding vascular dementia, which is currently seen as heterogeneous and not simply a consequence of strokes. We argue that the HIS is in fact an infarct score, that it is not a true dimensional scale, and that it has outlived its usefulness.

Concurrent validity of critical flicker fusion in patients with primary degenerative dementia of the Alzheimer type

AbstractThe concurrent validity of critical flicker fusion threshold (CFFT) and flicker threshold measurement was examined in 23 female and three male patients with primary degenerative dementia of the Alzheimer type (PDDAT). Patients had a mean age of 81.7 ± 6.05 years (range 67–89). Diagnosis of PDDAT was based on the DSM‐III‐R classification. Both the CFFT and flicker thresholds were found to be highly and significantly correlated with standardized clinical assessment (Global Deterioration Scale), cognitive function (Abbreviated Mental Test) and psychomotor performance (Choice Reaction Time). The implications of these two measures for clinical trial research and the longitudinal assessment of patients with Alzheimer's disease are discussed.

Primary degenerative dementia of the Alzheimer type in twins: Initial findings from the Maudsley Hospital Twin Register

AbstractIn detailed published accounts to date of 40 twin pairs one or both of whom were said to have Alzheimer's disease (AD), 16 of 35 monozygotic (MZ) pairs were described as concordant for the disease and the remaining 19 pairs as discordant, while of the five pairs of dizygotic (DZ) twins two pairs were designated as concordant. However, these data have emerged almost exclusively from selective case reports and volunteer samples, resulting in an over‐representation of MZ twins that complicates the overall interpretation of the data. In an effort to reduce such ascertainment bias, we screened for diagnoses consistent with AD in the Maudsley Hospital Twin Register, which consists of twins registered at the Bethlem Royal and the Maudsley Hospitals (London, UK) since 1948. Seven twins were identified who met criteria for primary degenerative dementia of the Alzheimer type. Available details of their affected status as well as of the status of their co‐twins are presented and discussed.

Does Computed Tomographic Brain Imaging Have a Place in the Diagnosis of Dementia?

Computed tomographic (CT) scanning of the head is an accepted routine in the evaluation of dementia. This study attempted to identify a patient group in which brain imaging adds meaningful data to the clinical picture. One hundred patients who met criteria for dementia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, underwent computed tomographic imaging. From clinical data alone, 56 of these patients also met the following strict criteria for the diagnosis of probable Alzheimer's disease (PAD): the McKhann criteria for PAD, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria for primary degenerative dementia, a score of less than 4 on the modified Hachinski Ischemia Scale, a normal neurologic examination and symptoms for at least 1 year. In the PAD group, eight scans (14%) had abnormalities other than atrophy; only three (two showing lacunae and one showing infarct) were of possible clinical significance. In the 44 patients not meeting PAD criteria, 23 scans (52%) were abnormal, including 15 with infarcts, two with periventricular lucencies, three showing tumors, and one showing hydrocephalus. These results support the diagnostic value of computed tomographic scanning in atypical dementia and its limited utility in PAD. The data indicate that clinical guidelines can be developed for the application of CT in the diagnosis of dementia.

Does computed tomographic brain imaging have a place in the diagnosis of dementia?

Computed tomographic (CT) scanning of the head is an accepted routine in the evaluation of dementia. This study attempted to identify a patient group in which brain imaging adds meaningful data to the clinical picture.One hundred patients who met criteria for dementia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, underwent computed tomographic imaging. From clinical data alone, 56 of these patients also met the following strict criteria for the diagnosis of probable Alzheimer's disease (PAD): the McKhann criteria for PAD, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria for primary degenerative dementia, a score of less than 4 on the modified Hachinski Ischemia Scale, a normal neurologic examination and symptoms for at least 1 year.In the PAD group, eight scans (14%) had abnormalities other than atrophy; only three (two showing lacunae and one showing infarct) were of possible clinical significance. In the 44 patients not meeting PAD criteria, 23 scans (52%) were abnormal, including 15 with infarcts, two with periventricular lucencies, three showing tumors, and one showing hydrocephalus.These results support the diagnostic value of computed tomographic scanning in atypical dementia and its limited utility in PAD. The data indicate that clinical guidelines can be developed for the application of CT in the diagnosis of dementia.

Impaired tactile pattern recognition in the early stage of primary degenerative dementia compared with normal aging

Tactile pattern recognition of ten different patterns which were engraved upon 4 × 4 cm plastic plaquettes with one hand and thereafter drawing with the other or the same hand was tested in 21 patients with a mild stage primary degenerative presenile onset dementia of Alzheimer type (DAT) and in 14 patients with a questionable dementia on the background of a chronic cardiovascular disease (CVD) in comparison to 15 healthy subjects of the same age (51 years old, elder controls, (EC)) and 16 younger subjects (22 years old, younger controls, (YC)). Patients made about four times more errors than the EC group. Duration from the begin of touching to the end of drawing was significantly longer in patients than in controls. In a second task the subjects had to recognize four subsequent patterns, then to perform a standard multiplication task and afterwards to draw all four patterns in their correct sequence. Patients made about ten times more errors in pattern recognition and series reproduction than age-matched controls.

Cerebrovascular responsiveness to hypercapnia in Alzheimer's dementia and vascular dementia of the Binswanger type.

Alzheimer's dementia is thought to be a primary degenerative dementia, whereas vascular dementia of the Binswanger type is an entity of vascular dementia. We evaluated the cerebrovascular responsiveness to hypercapnia to clarify the differences in the cerebral hemodynamics between two groups of patients. The subjects were eight younger control subjects, five age-matched control subjects, five Alzheimer's patients, and five patients with vascular dementia of the Binswanger type. In the resting state, the regional cerebral blood flow was low in both Alzheimer's dementia and vascular dementia of the Binswanger type. The responsiveness to hypercapnia was preserved in Alzheimer's dementia, whereas it was impaired in vascular dementia of the Binswanger type in the cerebral cortices and in the deep white matter. These results suggest that small vascular lesions exist in vascular dementia of the Binswanger type but not in Alzheimer's dementia, even though regional cerebral blood flow was thought to decrease by hypometabolism in both types of dementia.

Disruptive behaviors of a cognitively impaired nursing home resident

The descriptive case study of a 71-year-old man with Primary Degenerative Alzheimer's Dementia identifies and describes specific disruptive behaviors exhibited by a demented, disruptive nursing home resident and the biopsychosocial characteristics of these behaviors. The Disruptive Behavior Scale (Beck, Baldwin, Heithoff, & Cuffel, 1990) measured disruptive behaviors. Data collected included chart review, interviews, testing, and observation. The majority of observed disruptive behaviors fell under four categories: (1) walks aimlessly, (2) makes repetitive noises, (3) uses obscene/profane language, and (4) makes repetitive movements. Staff members and chart notes reported the same categories, except for “makes repetitive noises.” All aggressive behavior toward the staff occurred during assistance with activities of daily living (ADLs).

Brain computed tomography findings in geriatric depression and primary degenerative dementia

Brain computed tomography (CT) scans were performed in hospitalized geriatric patients with major depression (n = 45) or primary degenerative dementia (n = 21). Depressed patients with onset of illness at age 60 years or older (n = 32) had greater ventricular size than geriatric depressives with earlier age of illness onset (n = 3). CT parameters of late-onset depressives were comparable to those of patients with primary degenerative dementia. However, early-onset geriatric depressives had significantly smaller ventricles and less sulcal widening than demented patients. The findings suggest that late-onset depression may have a stronger association with neurological dementing disorders than early-onset depression.

CBF and cognitive evaluation of Alzheimer type patients before and after IMAO-B treatment: a pilot study

Ten patients diagnosed as affected by primary degenerative dementia of the Alzheimer type, with a mild to moderate cognitive and behavioral impairment, were studied in a double blind design when taking for 60 days 5 mg twice a day of L-deprenyl or placebp. Cognitive functions and cerebral blood flow were assessed at the beginning and at the end of treatment by a wide array of memory, attention, and language efficiency measures and by SPECT- 99TcHMPAO procedure. Reduced CBF on the parietal lobes was demonstrated in the patients at baseline together with a reduction of memory and cognitive efficiency. At the end of the treatment patients who received L-deprenyl showed an improvement in cognitive efficiency and no changes in CBF, while patients treated with placebo showed a worsening of cognitive efficiency and further reduction of parietal lobe CBF.

Is sleep deprivation useful in the treatment of depression?

The authors critically reviewed the literature on clinical applications of sleep deprivation in the treatment of depression. They included all studies using sleep deprivation for clinical purposes, with the exception of treatment studies that did not provide follow-up beyond a night of recovery sleep. They focused on six uses of sleep deprivation: 1) to potentiate response to antidepressant medication (13 studies), 2) to hasten the onset of action of antidepressant medication or lithium (five studies), 3) to prevent recurrent mood cycles (four studies), 4) as an alternative to antidepressant medication (five studies), 5) as a diagnostic probe (two studies), and 6) to predict response to antidepressant medication (nine studies). Although the literature appears to demonstrate the efficacy of sleep deprivation as a potentiation strategy, these treatment studies have substantial methodological shortcomings. Well-designed pilot studies indicate that sleep deprivation may hasten the onset of action of thymoleptic medications. Sleep deprivation may prevent premenstrual mood swings, and response to sleep deprivation may differentiate depressive pseudodementia from primary degenerative dementia with depression. Studies attempting to use sleep deprivation to predict response to antidepressant medication have yielded inconsistent results. Given the noninvasive nature of sleep deprivation, it would be useful to determine if even a small subset of refractory patients respond to it. The authors suggest future research directions to determine the usefulness of this potential treatment.

DSM-III-R criteria for primary degenerative dementia and multi-infarct dementia [corrected

Primary degenerative dementia (PDD) and multi-infarct dementia (MID) are the two most common categories of cognitive decline in old age. The definitions of these two clinical entities are currently based on clinical evaluation and on the exclusion of other underlying causes, and still lack a consensus. The DSM-III-R criteria are widely used for the diagnosis of dementia. However, their role in the differentiation between PDD and MID has not been thoroughly examined. A consecutive series of 98 demented patients who met the DSM-III-R criteria for dementia were admitted to a clinical study. Upon evaluating their type of dementia according to these criteria, 53 patients could not be diagnosed either as having PDD or MID. The DSM-III-R criteria for these two types of dementia are critically reviewed. Proposed modifications, aimed at refining their differential diagnostic role, are presented, enabling better allocation of demented patients into PDD, MID, or intermediate groups.

A new scale for assessing behavioral agitation in dementia

The primary purpose of the present study was to develop a reliable and valid rating instrument for assessing treatment efficacy for behavioral problems in the cognitively impaired elderly. The Behavioral and Emotional Activities Manifested in Dementia (BEAM-D) Scale was developed for the operational assessment of troublesome and disruptive behaviors in dementia. Each behavioral category of the BEAM-D was clinically considered to be a significant deviation from normative behavior for the geriatric dementia patient. The reliability and validity of the BEAM-D was assessed in a group of 45 patients diagnosed with primary degenerative dementia. The mean interrater reliability of BEAM-D items was 0.90. Concurrent validity was established by comparison with currently used rating scales, the Brief Psychiatric Rating Scale (BPRS) and the Sandoz Clinical Assessment-Geriatric (SCAG). Stepwise regression analysis revealed that the items of the BEAM-D had a strong relationship with conceptually similar behavioral dimensions on the BPRS and SCAG.

Spatial recognition and spatial order memory in patients with dementia of the Alzheimer's type

Patients diagnosed as having mild or moderate primary degenerative dementia of the Alzheimer's type (PDDAT), and normal elderly subjects were tested for spatial order and a spatial recognition memory. Results for spatial order memory indicated that compared to normal elderly subjects, patients with mild PDDAT showed an impaired memory only for the last serial positions. In contrasts, with respect to spatial recognition memory, patients with mild PDDAT showed an impaired memory only for the early serial positions. Patients with moderate PDDAT were impaired on all serial positions for both spatial order and spatial recognition memory. Based on comparable deficit patterns seen in animals and patients with hippocampal and parietal cortex lesions, it is suggested that memory deficits displayed by PDDAT patients might be a function of underlying pathology in the hippocampus and parietal cortex.

Primary Progressive Dementia with Swollen Chromatolytic Neurons

We report a case of dementia in which cortical degeneration with widespread presence of swollen chromatolytic neurons was the dominant pathologic feature. The previously healthy woman began to notice psychiatric symptoms at the age of 52 years. The symptoms and neurological signs progressed inexorably over the next 4 years. By the time of her death at 56 years of age, she was hopelessly disabled and lay in a mute, rigid, immobile, and seemingly insensate condition. Ultimately, quadriplegia in flexion and profound dysfunction of the extrapyramidal system, the ''akinetic-rigid syndrome'' were noted. In this patient the relentlessly progressive course, without remissions, suggests a degenerative process. Pathological examination showed frontoparietal atrophy with nerve cell loss and the presence of swollen chromatolytic cells, but there were no Pick bodies. There was nerve cell loss and gliosis in the pigmented portion of substantia nigra. Despite some pathological similarities to Pick''s disease we suggest that the distribution of nerve cell loss and the absence of Pick bodies and white matter lesions are unique to this case. Comparison of swollen chromatolytic neurons with other cerebral degenerative disorders indicates a similarity with corticonigral degeneration. This case could be included as a type of primary degenerative dementia.

Concerning the Distribution of Cerebral Muscarinic Acetylcholine Receptors in Alzheimer's Disease

To the Editor. —A recent article by Weinberger et al 1 describes the distribution of cerebral muscarinic acetylcholine receptors (mAChR) in vivo in patients with Alzheimer's disease (AD) using single photon emission computed tomographic (SPECT) imaging of the distribution of radioiodinated 3-quinuclidinyl-4-iodobenzilate ((R,R)-[ 123 I]IQNB), a specific radioligand for the mAChR. 2 The primary observation is that there is ... a significant reduction bilaterally in the posterior temporal cortex of the patients with Alzheimer's disease compared with controls... The authors conclude, ... It is likely that the images reflect the distribution of the relative density of a subpopulation of muscarinic receptors. The majority of the patients with primary degenerative dementia had qualitatively abnormal IQNB SPECT scans, perhaps because of focal areas of reduced receptor density... However, although it is possible that the (R,R)-[ 123 I]IQNB localization deficits reflect a mAChR deficit, as we show below, the argument presented to distinguish this possibility

Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer's disease: light and electron microscopic immunocytochemistry of CA2-3 neurites specific to DLBD.

Immunocytochemistry with antibodies to ubiquitin is currently the most sensitive method for detecting cortical Lewy bodies, which are a sine qua non for the diagnosis of diffuse Lewy body disease (DLBD), an increasingly recognized form of primary degenerative dementia. In the systematic application of ubiquitin immunocytochemistry to sections of hippocampus from control subjects and patients with a wide spectrum of neurodegenerative diseases, we noted the frequent occurrence of ubiquitin-immunoreactive neurites in the CA2-3 region in DLBD. The nature of these neurites was investigated with immunocytochemistry in DLBD, Alzheimer's disease (AD), normal elderly subjects, and Parkinson's disease (PD). Although the number of neurites varied from case to case, they were virtually always detected in DLBD but not in normal, AD, or PD brains. Double immunolabeling studies with anti-ubiquitin demonstrated a small fraction of double-stained neurites with antibodies to neurofilament or Alz-50, but no double staining with an antibody to Alzheimer neurofibrillary tangles. These results are different from those for neurites in AD, which are rarely seen in CA2-3 and which are immunoreactive with all these antibodies. Neuritic degeneration in the CA2-3 region of the hippocampus appears to be a specific histopathologic feature of DLBD.

Prospective neuropathological validation of Hachinski's Ischaemic Score in dementias.

The sensitivity and specificity of Hachinski's Ischaemic Score (IS) in the diagnosis of the vascular aetiology of dementia was studied in a series of 32 demented patients, dementia of the Alzheimer type (16), multi-infarct dementia (7), mixed dementia (6), Pick's disease (3), with neuropathological diagnosis as the point of reference. The IS distinguished between primary degenerative dementia and multi-infarct or mixed dementia. As single features of the IS "a positive history of stroke" and "a fluctuating course" showed differing prevalences in the latter two diagnostic categories. The IS labelled 21% of patients with primary degenerative dementia as having a vascular aetiology. The uncritical application of the IS to large samples in epidemiological studies may cause incorrect labelling of a significant proportion of patients with primary degenerative dementia as vascular dementia. These results are based on observations of long-term inpatients and depend on neuropathological criteria. While the definite diagnosis of DAT by threshold criteria concerning plaque and tangle counts is well established, neither clinical nor pathological evidence of stroke necessarily means that cerebrovascular disease has anything to do with a patient's dementia.

Reliability of flicker threshold measurement in patients with primary degenerative dementia of the Alzheimer's type (PDDAT)

AbstractThe test‐retest and split‐half reliability of flicker threshold measurement was determined in 23 female and three male patients with primary degenerative dementia of the Alzheimer's type (PDDAT). Patients had a mean age of 81.7 ± 6.05 years (range 67–89). Diagnosis of PDDAT was based on DSM‐IIIR criteria. The psychophysical method of limits was used to determine the flicker threshold and was the average of four separate measurements. The split‐half reliability was found to be 0.97 and the test‐retest reliability 0.941 (both p < 0.0001). The measurement of flicker thresholds is a quick, easy and reliable technique in patients with PDDAT. Future work will also need to examine the validity and pharmacosensitivity of the measure if it is to be used to assess potentially therapeutic agents for the management of the underlying disease process.

Autobiographical Memory in Normal Aging and Primary Degenerative Dementia (Dementia of Alzheimer Type)

Autobiographical memory of old people (71-89 years) was studied by a method of free narratives, with normal subjects as well as patients with primary degenerative dementia (SDAT) at three stages of development. The chronological distribution of memories across the life span in both groups showed a peak in adolescence and early adulthood, decrease in mid-life, and increase in recent years. This distribution is different from the results found with the prompt word method among normal old adults, but is similar to the chronological pattern reported for vivid memories. The distribution in the demented group was more flat, which contradicts theories of selective preservation of early memories. With the progression of dementia, autobiographical memory deficits were first evidenced by inaccessibility or loss of memories, and, at a later stage, by loss of details of the retrieved memories and impairment of temporal structure. Events that marked transitions in the lives of the patients ("landmarks") were less subject to forgetting than nontransitional events. The article argues for an approach to autobiographical memory that takes into account sociocultural and developmental determinants of memorability as well as internal mechanisms of the cognitive system.