No family history of psychiatric disorders, such as schizophrenia, bipolar disorder, or dementia, was reported (Table 1).
The authors’ observations
The existence of LOS as a distinct subtype of schizophrenia has been the subject of discussion and controversy as far back as Manfred Bleuler in 1943 who coined the term “late-onset schizophrenia.”1 In 2000, a consensus statement by the International Late-Onset Schizophrenia Group standardized the nomenclature, defining LOS as onset between age 40 and 60, and very-late-onset schizophrenia-like psychosis (VLOS) as onset after age 60.2 Although there is no diagnostic subcategory for LOS in DSM, DSM-5 notes that (1) women are overrepresented in late-onset cases and (2) the course generally is characterized by a predominance of psychotic symptoms with preservation of affect and social functioning.3 DSM authors comment that it is not yet clear whether LOS is the same condition as schizophrenia diagnosed earlier in life. Approximately 23% of schizophrenia cases have onset after age 40.4
Cognitive symptoms in LOS
The presence of cognitive deficits in schizophrenia is common and well-recognized. The intellectual impairment is generalized and global, and there also is specific impairment in a range of cognitive functions, such as executive functions, memory, psychomotor speed, attention, and social cognition.5 Typically these cognitive impairments are present before onset of psychotic symptoms. Although cognitive symptoms are not part of the formal diagnostic criteria, DSM-5 acknowledges their presence.3 In a systematic review on nature and course of cognitive function in LOS, Rajji and Mulsant6 report that global deficits and specific deficits in executive functions, visuospatial constructional abilities, verbal fluency, and psychomotor speech have been found consistently in studies of LOS, although the presence of deficits in memory, attention, and working memory has been less consistent.
The presence of cognitive symptoms in LOS is less well-studied and understood (Table 2). The International Consensus Statement reported that no difference in type of cognitive deficit has been found in early–onset cases (onset before age 40) compared with late-onset cases, although LOS is associated with relatively milder cognitive deficits. Additionally, premorbid educational, occupational, and psychosocial functioning are less impaired in LOS than they are in early-onset schizophrenia.2
Rajji et al7 performed a meta-analysis comparison of patients with youth-onset schizophrenia, adults with first-episode schizophrenia, and those with LOS on their cognitive profiles. They reported that patients with youth-onset schizophrenia have globally severe cognitive deficits, whereas those with LOS demonstrate minimal deficits on arithmetic, digit symbol coding, and vocabulary but larger deficits on attention, fluency, global cognition, IQ, and visuospatial construction.7
There are conflicting views in the literature with regards to the course of cognitive deficits in schizophrenia. One group of researchers believes that there is progressive deterioration in cognitive functioning over time, while another maintains that cognitive impairment in schizophrenia is largely “a static encephalopathy” with no significant progression of symptoms.8 A number of studies referenced by Rajji and Mulsant6 in their systematic review report that cognitive deficits seen in patients with LOS largely are stable on follow-up with an average duration of up to 3 years. However, 2 studies with longer follow-up report evidence of cognitive decline.9,10
Relevant findings from the literature. Brodaty et al9 followed 27 patients with LOS without dementia and 34 otherwise healthy participants at baseline, 1 year, and 5 years. They reported that 9 patients with LOS and none of the control group were found to have dementia (5 Alzheimer type, 1 vascular, and 3 dementia of unknown type) at 5-year follow-up. Some patients had no clinical signs of dementia at baseline or at 1-year follow-up, but were found to have dementia at 5-year follow-up. The authors speculated that LOS might be a prodrome of Alzheimer-type dementia.
Kørner et al10 studied 12,600 patients with LOS and 7,700 with VLOS, selected from the Danish nationwide registry; follow-up was 3 to 4.58 years. They concluded that patients with LOS and VLOS were at 2 to 3 times greater risk of developing dementia than patients with osteoarthritis or the general population. The most common diagnosis among patients with schizophrenia was unspecified dementia, with Alzheimer’s dementia (AD) being the most common diagnosis in control groups. The findings suggest that dementia in LOS and VLOS has a different basis than AD.
Zakzanis et al11 investigated which neuropsychological tests best differentiate patients with LOS and those with AD or frontotemporal dementia. They reported that Wechsler Adult Intelligence Scale-Revised (WAIS-R) Similarities subtest and the California Verbal Learning Test (both short- and long-delay free recall) can differentiate LOS from AD, and a test battery comprising the WAIS-R Vocabulary, Information, Digit Span, and Comprehension subtests, and the Hooper Visual Organization test can differentiate LOS and frontotemporal dementia.12