Thomas A. Ban: Neuropsychopharmacology in Historical Perspective. Dementia Differential Diagnosis 


Dementing Illnesses


Senescent forgetfulness

       The origin of the diagnostic concept of "senescent forgetfulness" (SF) was in the work of Kral (1959) who was the first to demonstrate that SF consists of two distinctive diagnostic groups he referred to as "benign senescent forgetfulness" (BSF) and "malignant senescent forgetfulness" (MSF).

       Within Kral's (1982) dichotomy, BSF represents an anomaly of recall with an effect on events in subjects’ remote memory; and is characterized by forgetfulness which remains restricted to relatively unimportant details, such as names and places, in subjects’ experience in the distant past which are not accessible for recollection at one time but can be recalled at another time. Another important characteristic of BSF is that it does not extend to include the event of which the "unimportant details" are an integral part; and since registration and retention are preserved, it leaves the key experience accessible for recollection at any time. The third and final characteristic of BSF is that subjects are keenly aware and concerned about their forgetfulness.

       MSF, in variance with BSF, represents an anomaly of recall with an effect on events in subject’s recent memory; and is characterized by forgetfulness which does not remain restricted to relatively unimportant details, but extends to the event and/or experience of which the unimportant details are an integral part. Another important characteristic of MSF is disorientation, at first to time and place, but later on to personal data, memories. The third and final characteristic of MSF is that subjects are unaware of their deficit and, as a result, not concerned about their forgetfulness.

       Almost 30 years after the introduction of the concept of BSF, Crook, Bartus, Ferris et al. (1986) proposed the introduction of a similar diagnostic concept, referred to as Age Associated Memory Impairment (AAMI); and developed criteria on the basis of which AAMI can be reliably diagnosed. An important impetus in the formulation of these diagnostic criteria were the findings that in variance with sensory, primary (short-term or immediate) and tertiary (remote) memories, which were little affected, secondary (recent or long­ term) memory clearly showed substantial age-related deficits at early stages of the aging process, when the performance of old and young individuals were compared.


Senile Dementia of the Alzheimer’s Type

Unitary Concept; AD

       The origin of the diagnostic concept to become known as Alzheimer's disease (AD) was in the description of the clinical manifestations and the underlying neuropathologic changes in a 51-year-old female admitted to the Psychiatric Clinic of the University of Frankfurt in November 1901. During her hospitalization, the patient displayed a "relentlessly progressive dementia" with aphasia, disorientation and paranoid thinking, leading to death within a relatively short period of time. At the beginning, Alzheimer in 1901 himself was hesitant to designate this rather dramatic clinical presentation as a nosologic entity. Therefore, it was only upon the insistence of Emil Kraepelin (1909-1915) that the early onset, rapidly progressing, deadly dementia with cerebral atrophy, ventricular enlargement associated with agnosia, aphasia and apraxia Alzheimer described in 1901 became known as Alzheimer's disease (AD) (Koranyi 1988).

       Since Alzheimer (1907) identified the disease on the basis of specific histopathologic findings, to date, the hallmarks of the disease have remained the presence of argentophil (senile neurotic) plaques and neurofibrillary tangles.


Dichotomy: AD vs SDAT

       In the eighth edition of his textbook, Kraepelin (1909) separated late onset senile dementia (SD) from the early onset presenile dementia of AD. Nevertheless, since apart from the arbitrary dividing line of 85 years of age, no qualitative difference between the two could be identified (Kidd 1984). During the 19T0s the early onset and late onset disease were pooled together under the diagnostic concept of senile dementia of the Alzheimer's type (SDAT) (Terry and Wisniewski 1975).

       In spite of all the similarities, however, Bondareff, Mountjoy and Roth (1982) focused attention on the biologic heterogeneity of the population subsumed under SDAT. They contended that early onset presenile dementia (AD) differs from late onset senile dementia (SD) by its rampant course, greater parietal lobe involvement, more prominent ventricular enlargement and profound impairment of cholinergic functioning. Further support of the dichotomy was provided by Roth (1985), who separated a late onset, Type I (SD), and an early onset, Type II (AD), syndrome and characterized the former by its continuity and the later by its contiguity with normal aging.


Trichotomy: AD vs SD vs SDAT

       In their family genetic study, Heston and Mastri (1977) recognized that Down's syndrome and blood dyscrasias (e.g., leukemia and Hodgkin's disease) are encountered significantly more often among first degree relatives of AD patients (but not of SDAT patients) than in the general population. In view of this, and with consideration to postmortem neuropathologic findings which clearly indicate that there are late onset dementias without Alzheimer's lesions, Gottfries (1989) suggests that within the late onset dementias, the distinction between SD and SDAT should be retained, even if the two are clinically indistinguishable.


Multi-Infarct Dementia

0riginal Concept

       The origin of the concept of multi-infarct dementia (MID) was in the discovery of a positive relationship between the occurrence of dementia and of multiple cerebral infarcts - with a loss of more than 50-100 ml of cerebral volume - at autopsy (Tomlinson, Blessed and Roth 1970, 1988). The term was coined by Hachinski, Lassen and Marshall (1974) who characterized MID by abrupt onset, stepwise deterioration and fluctuating course.

       For the diagnosis of MID, and for the separation of MID from SDAT, a simple assessment instrument, based on 13 variables relevant to the evaluation of cerebral ischemia, was developed by Hachinski, Ilif, Zilkha et al. (1975) (Table 4).  The original Hachinski scale, a highly reliable assessment instrument which had been validated in a series of autopsies, was modified by Rosen, Terry, Fuld et al. (1980). The modified scale, which consists of 8 of the original 13 variables, is a reliable and valid instrument for the separation of MID from the Alzheimer's type of dementia.

Table 4










Abrupt Onset




Stepwise deterioration




Fluctuating course




Nocturnal confusion




Relative perseveration of personality








Somatic complaints




Emotional incontinence




History of presence of hypertension




History of stroke




Evidence of associated atherosclerosis




Focal neurological symptoms




Focal neurological signs








Maximal score




Maximal score for NID




Maximal score for SDAT






Comparison of Original and Modified Hachinski ischemic Score. Numbers indicate point values assigned to each feature in the original score proposed by Hachinski, Ilif, Zilkha et al. (1975) and in the modified version proposed by Rosen, Terry, Fuld et al. (1980). Maximal unmodified score for NID Multi-infarct dementia) and maximal unmodified score for SDAT (senile dementia of the Alzheimer type are those proposed by Hachinski. Modified score guidelines for the diagnosis of NID and SDAT are based on the experience of Blass and Barclay (1986).


August 19, 2021